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Objective To investigate the effect of glucagon-like peptide 1(GLP-1)receptor agonists exendin-4 on the secretion of cyclophilin A(CyPA)to inhibit atherosclerosis(AS)and vascular calcification in mice role of the process.Methods Twenty ApoE-/-mice were randomly divided into model group and exendin-4 group,10 mice in each group,and were fed with high-fat diet to establish AS model,another 10 wild-type C57BL/6J mice were taken as the control group,and the exendin-4 group was intraperitoneally injected with the GLP-1R agonist exendin-4,1/d,for 8 weeks.After 8 weeks,the ELISA method was used to determine the level of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and CyPA,serum calcium level was detected by methylthymol blue colorimetric method,oil red O staining to detect the development of atherosclerotic plaques in the aorta,HE staining was used to observe the pathological changes of the aorta,Von Kossa staining was used to observe the calcium deposition in the aorta,immunohistochemical staining,Real-time PCR and Western blotting were used to detect the expression levels of aortic RUNX2 and bone morphogenetic protein 2(BMP-2),immunofluorescent staining was used to detect the positive expression of CyPA in aortic tissue.Results Compared with the control group,the serum levels of TG,TC,LDL-C,Ca and CyPA in the model group increased(P<0.05),the atherosclerotic plaque areas of the aorta increased(P<0.05),the aortic wall was thickened significantly and a large number of inflammatory cells were infiltrated,a large amount of calcium deposits were deposited in the aortic parietal membrane,the positive expression area ratio of RUNX2 and BMP-2,the relative mRNA expression of RUNX2 and BMP-2,the relative protein expression of RUNX2 and BMP-2 in aortic tissue all increased(P<0.05),and the red fluorescence of CyPA expression in aortic tissue was enhanced significantly.Compared with the model group,the serum levels of TG,TC,LDL-C,Ca and CyPA in the exendin-4 group decreased(P<0.05),the atherosclerotic plaque areas of the aorta decreased(P<0.05),the thickening of the aortic wall and the infiltration of inflammatory cells were alleviated significantly,the calcium deposition in the aortic wall was reduced,the positive expression area ratio of RUNX2 and BMP-2,the relative mRNA expression of RUNX2 and BMP-2,the relative protein expression of RUNX2 and BMP-2 in aortic tissue all decreased(P<0.05),and at the same time,the red fluorescence of CyPA expression in aortic tissue was weakened significantly.Conclusion GLP-1 receptor agonists exendin-4 can inhibit atherosclerosis and vascular calcification in mice,and the mechanism may be related to the reduction of CyPA secretion.
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Objective Taking Sortilin as the entry point,this study aims to explore the mechanism of vascular calcification in chronic renal failure(CRF)and explore the influence of Sanqi on Sortilin,TLRs and vascular calcification,and to provide an effective method for clinical reduction of cardiovascular events in CRF.Methods Thirty-six male SD rats were randomly divided into normal group,model group,low-,medium-and high-dose Sanqi group and calcitriol group,with 6 rats in each.The replicative CRF vascular calcification rat model was fed with adenine combined with high phosphorus diet.Aortic calcium salt deposition,serum creatinine(Scr),urea nitrogen(BUN),blood calcium(Ca),blood phosphorus(P),total cholesterol(TC),triglyceride(TG),TLRs and Sortilin protein in aorta and inflammatory factors were detected.Results In the model group,renal fibrosis was obvious and many adenine crystals were found in renal interstitium.Large deposits of calcium salts were found.Renal fibrosis and calcium salt deposition were alleviated in different degrees in all treatment groups.Compared with those in the normal group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of the model group was ascended(P<0.01),while the level of Ca was descended(P<0.01).Compared with those in the model group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of rats in the Sanqi medium and high dose group and calcitriol group was significantly decreased(P<0.01),and the contents of Ca were significantly increased(P<0.05 or P<0.01).Compared with those in the normal group,the protein expression of BMP2,RUNX2,Sortilin,TLR7 and TLR9 in aortic tissue of rats in the model group was elevated(P<0.01),while the protein expression of SM22α was declined(P<0.01).Compared with those in the model group,the protein expression of BMP2,RUNX2,Sortilin,TLR7,and TLR9 in the low-,medium-,and high-dose Sanqi group and calcitriol group was decreased significantly(P<0.01);the protein expression of SM22α was increased significantly(P<0.05 or P<0.01),and the high-dose Sanqi group and calcitriol group had more significant effects.Conclusion Sanqi can improve renal fibrosis and vascular calcification in CRF model rats,and its mechanism may be related to the regulation of biological functions of Sortilin and TLRs.
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BACKGROUND:CXC motif chemokine 5(CXCL5)is a neutrophil activating peptide derived from epithelial cells,which may be involved in arterial diseases.However,there is yet no report on the effect of CXCL5 in vascular calcification. OBJECTIVE:To explore the role of CXCL5 in the vascular calcification of carotid atherosclerosis(CAS). METHODS:(1)Cytological experiment:Mouse vascular smooth muscle cells(VSMCs)were divided into five groups:osteogenic medium group,Vector group(vector,blank plasmid transfected into VSMCs),CXCL5 group(CXCL5 plasmid transfected into VSMCs),si-NC group(CXCL5 negative control siRNA transfected into VSMCs),si-CXCL5 group(CXCL5 siRNA transfected into VSMCs),Vector+LY2157299 group and CXCL5+LY2157299 group(LY2157299 transferred into the cells 24 hours after cell transfection).Alizarin red staining,alkaline phosphatase staining,and calcium content determination were performed to evaluate the osteogenic differentiation level of VSMCs.(2)Animal experiment:Forty-eight ApoE-/-mice were randomly divided into four groups(n=12 per group):Con+si-NC group,Con+si-CXCL5 group,CAS+si-NC group and CAS+si-CXCL5 group.Animal models were not prepared in the first two groups,in which si-NC or si-CXCL5 lentivirus was injected into the tail vein;carotid atherosclerosis models were made in the latter two groups,in which si-NC or si-CXCL5 lentivirus was injected into the tail vein.Von Kossa staining and immunohistochemical staining were used to evaluate carotid vascular calcification and the expression of CXCL5 and transforming growth factor-β receptor 1(TGFBR1)in mice. RESULTS AND CONCLUSION:In the CXCL5 group,the protein level of runt-related transcription factor 2(RUNX2)was up-regulated and the level of α-smooth muscle actin was down-regulated,in contrary to the findings in the si-CXCL5 group.In addition,CXCL5 overexpression upregulated the level of TGFBR1,while CXCL5 knockdown inhibited the level of TGFBR1.Compared with the Vector group,the intensity of alizarin red staining,alkaline phosphatase activity and calcium content in the CXCL5 group increased significantly(P<0.05).Compared with the si-NC group,the intensity of alizarin red staining,alkaline phosphatase activity and calcium content in the si-CXCL5 group decreased significantly(P<0.05).When LY2157299 inhibited TGFBR1 expression,the osteogenic differentiation of VSMCs induced by CXCL5 was reduced.Compared with the Con+si-NC group,the expression of CXCL5 protein in the carotid artery and calcification area in the CAS+si-NC group increased significantly(P<0.05).Compared with the CAS+si-NC group,the expression of CXCL5 protein in the carotid artery and vascular calcification area in the CAS+si-CXCL5 group decreased significantly(P<0.05).In addition,compared with the Con+si-NC group,the expression of RUNX2 protein in the carotid artery in the CAS+si-NC group increased significantly(P<0.05),while the expression of α-smooth muscle actin protein decreased significantly(P<0.05).Compared with the CAS+si-NC group,the expression of RUNX2 protein in the carotid artery in CAS+si-CXCL5 group decreased significantly(P<0.05),while the expression of α-smooth muscle actin protein increased significantly(P<0.05).In conclusion,CXCL5 can induce osteogenic transformation of VSMCs by activating the TGFBR1 pathway,and inhibition of CXCL5 expression is effective in improving carotid arterial calcification in CAS mice.
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BACKGROUND:There is an internal relationship between hyperhomocysteinemia and vascular calcification.However,the pathogenesis of hyperhomocysteinemia promoting vascular calcification is still unclear. OBJECTIVE:To investigate the role of bone morphogenetic protein-2 in hyperhomocysteinemia-induced vascular calcification. METHODS:Human carotid wax samples were divided into a calcified group(n=29)and a non-calcified group(n=13)according to the presence or absence of calcified plaque.Sixteen ApoE-/-mice were randomly divided into a control group and a hyperhomocysteinemia group,with 8 mice in each group.Bone morphogenetic protein-2 vector was used to transfect rat thoracic artery smooth muscle A7r5 cells,and gradient concentration of homocysteine(50,100,200,and 400 μmol/L)was utilized to treat A7r5 cells.Calcification was detected by alizarin red staining and hematoxylin-eosin staining.The interaction of bone morphogenetic protein 2 with Runt-related transcription factor 2 was detected by immunofluorescence,and the expressions of bone morphogenetic protein 2,Runt-related transcription factor 2,and α-smooth muscle actin were detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION:(1)Human carotid artery tissue staining revealed that compared with the non-calcification group,inflammatory cells increased and calcification positive rate increased in the calcification group(P<0.05).Compared with the non-calcification group,the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated,and the expression of α-smooth muscle actin was decreased in the calcification group(all P<0.05).(2)The staining of mouse arterial specimens exhibited that,the positive rate of calcified area in the hyperhomocysteinemia group was significantly higher than that in the control group(P<0.05);serum homocysteine level in the hyperhomocysteinemia group was significantly higher than that in the control group(P<0.05).Compared with the control group,the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated,and the expression of α-smooth muscle actin was decreased in the hyperhomocysteinemia group(all P<0.05).(3)A7r5 cell culture analysis demonstrated that with the increase of homocysteine concentration gradient,the degree of calcification,the content of bone morphogenetic protein-2 and Runt-related transcription factor 2 protein in A7r5 cells increased(P<0.05),and the content of α-smooth muscle actin protein decreased(P<0.05).(4)The A7r5 cell culture analysis of overexpressed bone morphogenetic protein 2 showed that the calcification degree of the overexpressed bone morphogenetic protein 2 group was increased compared with the corresponding control group,the β-sodium glycerophosphate group,and the homocysteine group.RUNt-related transcription factor 2 expression up-regulated(P<0.05)and α-smooth muscle actin expression down-regulated(P<0.05).(5)The expression of bone morphogenetic protein 2 increased in A7r5 cells cultured with homocysteine in calcified medium,and the expression of Runt-related transcription factor 2 increased with the increase of bone morphogenetic protein 2 expression.(6)The results confirm that bone morphogenetic protein-2 is a key target gene in the regulation of smooth muscle cell phenotypic transformation resulting in vascular calcification by hyperhomocysteinemia.Targeted regulation of bone morphogenetic protein-2 reduces hyperhomocysteinemia-induced vascular calcification.
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Objective To construct a lentiviral vector for overexpression of bone morphogenetic protein 7(BMP7)in mice,and the effect of BMP7 overexpression on the expression of Jagged1 in mouse aortic endothelial cells and the calcification of the co-cultured vascular smooth muscle cells(VSMCs)were analyzed.Methods According to the target gene information Mouse-BMP7(NM_007557.3)and plasmid information pLVX-zsGreen-C1,gene sequence synthesis was carried out to construct BMP7 overexpression lentivirus.The efficiency of BMP7 overexpression lentivirus infection was detected by qPCR;the expression of Jagged1 protein in aortic endothelial cells from infected mice was detected by Western blot.The endothelial cells with lentivirus overexpressing BMP7 were co-cultured with VSMCs,and the calcification of VSMCs was observed by alizarin red staining.Results BMP7 overexpression lentiviral vector was successfully constructed and transfected into aortic endothelial cells.qPCR test results showed that the expression level of BMP7 mRNA was significantly increased in the BMP7 overexpression group than that in the normal control group(P<0.01),while there was no significant difference in the expression of BMP7 mRNA between the empty vector control group and the normal control group(P>0.05).Western blot results showed that the expression level of Jagged1 protein in endothelial cells of mouse in the BMP7 overexpression group was significantly lower than that in the normal control group(P<0.01),while there was no significant difference in the expression level of Jagged1 protein in endothelial cells between the empty vector control group and the normal control group(P>0.05).The results of alizarin red staining showed that the calcification of VSMCs was significantly increased after co-cultured with endothelial cells infected with BMP7 lentivirus.Conclusion Mouse BMP7 overexpression lentiviral vector was successfully constructed,and overexpression of BMP7 can reduce the expression of Jagged1 in mouse aortic endothelial cells and promote the calcification of co-cultured VSMCs.
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La aterectomía rotacional es un procedimiento específico utilizado para el manejo de lesiones coronarias complejas, especialmente cuando existe calcificación de las arterias coronarias (CAC). Esta técnica fue muy utilizada hasta la última década del siglo pasado; actualmente, aunque es poco usada, juega un papel importante en pacientes que podrían ser candidatos a revascularización quirúrgica pero que, por diferentes patologías ―como la enfermedad ateromatosa difusa, en la que se requieren estents largos, reestenosis in-stent, lesiones ostiales calcificadas y oclusiones totales crónicas―, se rechaza la opción quirúrgica. La aterectomía rotacional es un método que utiliza una fresa recubierta de diamante para reducir el volumen de las placas ateroescleróticas y la calcificación de los vasos. Este dispositivo dispersa la placa en microfragmentos, con lo que se consigue un aumento del diámetro luminal. Estos fragmentos, que tienen un diámetro mínimo, pasan predominantemente a la circulación capilar y luego son absorbidos por el sistema reticuloendotelial. Dentro de las complicaciones de esta técnica destacan la disección arterial, el atrapamiento del dispositivo, la bradicardia y la microperforación de arterias coronarias. Esta última puede ser corregida con el uso de trombina, de grasa subcutánea o de perlas. Este artículo reporta el caso de una paciente anciana con enfermedad coronaria multivaso asociada a calcificación extensa de todas las arterias coronarias, por una historia de radioterapia recibida en años anteriores por cáncer de mama y que, al no ser candidata a terapia quirúrgica por cirugía cardiovascular, requirió manejo con aterectomía rotacional que se vio complicada por microperforación de una arteria coronaria, pero que posteriormente evolucionó de manera satisfactoria.
Rotational atherectomy is a specific procedure for managing complex coronary artery lesions, especially when there is coronary artery calcification (CAC). This technique was widely used until the last decade of the 20th century; however, although it is rarely used, it currently plays an important role in patients who could be candidates for surgical revascularization but reject surgeries due to different pathologies-such as diffuse atheromatous disease requiring long stents, in-stent restenosis, calcified ostial lesions and chronic total occlusions. Rotational atherectomy is a method that uses a diamond-coated burr to reduce the volume of atherosclerotic plaques and calcification of vessels. This device breaks up plaque into microfragments, leading to an increase in lumen diameter. These fragments, which have a tiny diameter, pass predominantly into the capillary circulation and are then absorbed by the reticuloendothelial system. Among the complications of this technique are arterial dissection, device entrapment, bradycardia and microperforation of coronary arteries. The latter can be corrected with the use of thrombin, subcutaneous fat or beads. This article reports the case of an elderly female patient with multivessel coronary artery disease associated with extensive calcification of all the coronary arteries secondary to radiotherapy received in previous years for breast cancer. The patient, not being a candidate for cardiovascular surgery, required a rotational atherectomy that resulted in a microperforation of a coronary artery but with good subsequent progress.
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Introduction: With declining kidney function, the prevalence of vascular calcifications increases and calcification occurs years earlier and is more severe in chronic kidney disease (CKD) patients than in general population. We did this study to find the prevalence of vascular calcification in patients on maintenance hemodialysis using simple and inexpensive radiological method and to find out the correlation of vascular calcification score with vascular disease events, cardiovascular and all-cause mortality over a follow-up period of 1 year. Materials and methods: This prospective, observational, comparative, follow-up, single-center study of maintenance hemodialysis patients was performed at a tertiary care center in Haryana. Seventy-one patients on maintenance hemodialysis for more than 3 months were included in the study. Patients who were 18 years of age or below, CKD stage 5 patients not on dialysis and those who had previous history of parathyroidectomy were excluded. Adragao score for vascular calcification was calculated by evaluating bilateral iliac, femoral and radial arteries in plain radiographic films of pelvis and hands. Statistical analyses were performed with the SPSS System 10.0. Results: Seventy-one patients were enrolled in this study out of which, 45 were male and 26 were female. Mean age of patients was 61.92 ± 10.77 years. Majority of patients were elderly (age group ?60 years). Out of 71 patients, 66 (92.9%) were hypertensive and 26 (36.6%) patients were diabetic. Twenty-two (30.9%) patients had cardiovascular disease (CVD) at baseline. Coronary artery disease (CAD) was present in 20 (28.1%) patients, cerebrovascular disease was present in 2 (2.8%) patients and peripheral artery disease (PAD) was present in only 1 patient at baseline. Average dialysis duration received by patients was 21.35 ± 21.17 months. Out of 71 patients, 16 (22.5%) received calcium-containing phosphate binder, 51 (71.8%) received noncalcium-containing phosphate binder and 4 patients received no phosphate binder. Fifty-five (77.4%) patients received therapeutic or prophylactic vitamin D3 therapy during the study period. Vascular calcification detected with plain X-ray of pelvis and both wrists was found in 56.3% of patients on maintenance hemodialysis. The prevalence and severity of vascular calcification was higher with increasing age. Diabetes was found to be significantly associated with the presence of vascular calcification (p < 0.0005). CAD at the time of enrollment was significantly associated with vascular calcification (p = 0.009). Serum levels of calcium, phosphate, vitamin D3, intact parathyroid hormone (PTH), calcium-phosphate product or use of phosphate binders or the types or vitamin D therapy did not correlate clinically with presence of vascular calcification. Hemodialysis duration did not correlate with the presence of vascular calcification (p = 0.113). Presence of vascular calcifications in hemodialysis patients predicted future vascular disease events over 1 year follow-up (p = 0.013) but did not correlate with cardiovascular and all-cause mortality. Conclusion: There is a high prevalence of vascular calcification in maintenance hemodialysis patients in our center. The risk factors of vascular calcification were higher age, diabetes and CAD. These patients should be followed-up regularly for vascular events. We also want to reiterate with this study that plain X-ray is sufficient to rule out vascular calcification in CKD patients and should be employed regularly in dialysis clinics.
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RESUMEN Introducción : Los puntajes de riesgo cardiovascular tienen limitaciones relacionadas con la calibración, la discriminación y la baja sensibilidad. Se han identificado diferentes "moduladores de riesgo" que permiten mejorar la estratificación del riesgo cardiovascular: placa aterosclerótica carotídea (PAC), puntaje de calcio arterial coronario (pCAC) y lipoproteína(a) [Lp(a)]. Objetivos : 1) determinar la prevalencia de los moduladores de riesgo citados en una población en prevención primaria; 2) determinar la concordancia entre los 2 métodos de detección de aterosclerosis subclínica; 3) establecer qué proporción de pacientes deberían recibir estatinas inicialmente, según su puntaje de riesgo, y posteriormente con el conocimiento de los moduladores de riesgo. Material y métodos : Se incluyeron individuos de 18 a 79 años, que asistieron para una evaluación de riesgo cardiovascular y que no estaban recibiendo tratamiento hipolipemiante. Se calculó el puntaje de riesgo (ASCVD Risk Estimator) en cada paciente. Se evaluó la presencia de PAC, el pCAC y el nivel plasmático de Lp(a). Resultados : Se incluyeron 348 pacientes (edad media 55,6 ± 12,2 años, 45,4% hombres). En la población total, 29,8%, 36,8% y 53,2% de los pacientes mostraron un valor de Lp(a) ≥ 50 mg/dL, PAC o un pCAC > 0, respectivamente. La prevalencia de PAC y pCAC fue progresivamente mayor según la categoría de riesgo cardiovascular; sin embargo, la proporción de sujetos de bajo riesgo que tenían moduladores de riesgo fue considerable (Lp(a) ≥ 50 mg/dl: 25,7%; PAC: 22%; pCAC > 0: 33%). En los 60 individuos menores de 45 años la prevalencia de pCAC > 0 y PAC fue de 18,3% y 10%, respectivamente. La concordancia entre los dos métodos para determinar la presencia de ateromatosis subclínica fue discreta (kappa 0,33). La indicación del tratamiento con estatinas aumentó un 31,6% luego de evaluar la presencia de moduladores. Conclusión : La presencia de moduladores de riesgo fue frecuente en esta población en prevención primaria, incluso en sujetos de bajo riesgo o menores de 45 años. La detección de moduladores de riesgo podría mejorar la estratificación inicial y llevar a reconsiderar el tratamiento con estatinas.
ABSTRACT Background : Cardiovascular risk scores have limitations related to calibration, discrimination, and low sensitivity. Different "risk modulators" have been identified to improve cardiovascular risk stratification: carotid atherosclerotic plaque (CAP), coronary artery calcium (CAC) score and lipoprotein(a) [Lp(a)]. Objectives : The aims of this study were: 1) to determine the prevalence of risk modulators mentioned in a primary prevention population; 2) determine the concordance between the 2 methods of detecting subclinical atherosclerosis; and 3) establish which proportion of patients should receive statins according to the initial risk stratification and after being recategorized by screening for risk modulators. Methods : Individuals aged 18 to 79 years who consulted for cardiovascular risk assessment and who were not receiving lipid-lowering treatment were included. The risk score was calculated in each patient using ASCVD Risk Estimator. The presence of CAP, CAC score and Lp(a) level were evaluated. Results : The cohort was made up of 348 patients; mean age was 55.6 ± 12.2 years and 45.4% were men. In the total population, 29.8%, 36.8%, and 53.2% of patients showed Lp(a) value ≥50 mg/dL, CAP, or a CAC score >0, respectively. The prevalence of CAP and CAC score was progressively higher according to the cardiovascular risk category; however, the proportion of low-risk subjects who had risk modulators was considerable (Lp(a) ≥50 mg/dl: 25.7%; CAP: 22%; CAC score >0: 33%). In the 60 subjects <45 years, the prevalence of CAC score >0 and CAP was 18.3% and 10%, respectively. The agreement between the two methods for quantifying subclinical atheromatosis was fair (kappa= 0.33). The indication for statin treatment increased by 31.6% after evaluating the presence of modulators. Conclusion : The presence of risk modulators was common in this population in primary prevention, even in low-risk subjects or < 45 years. Detection of risk modulators could improve initial stratification and lead to reconsideration of statin treatment.
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Fundamento: As calcificações de artérias coronárias (CAC) mostram-se como fator preditivo de doenças cardiovasculares (DCV). A tomografia computadorizada (TC) de tórax com protocolo de aquisição de baixa dose apresenta acurácia na identificação de CAC e propicia achados incidentais dessas calcificações, que são comumente negligenciados. Este estudo analisará a prevalência de achados incidentais de calcificação em artérias coronárias em indivíduos não cardiopatas submetidos à TC de tórax. Métodos: Estudo transversal consecutivo de caráter analítico e descritivo. Foram incluídos indivíduos de ambos os sexos que realizaram TC de tórax por encaminhamento, acima de 18 anos e não cardiopatas. A coleta de dados foi realizada por meio de prontuários e ficha de anamnese auto aplicada. As variáveis referentes às CAC e à extensão do comprometimento foram obtidas a partir da reavaliação das imagens de TC de tórax disponíveis no sistema da instituição. Os exames foram anonimizados e avaliados por dois médicos radiologistas experientes. Considerou-se como estatisticamente significativo p≤0,05. Resultados: Foram analisados 397 exames. Encontrou-se prevalência de calcificações em 176 (44%) dos casos. A existência dessas calcificações coronárias está relacionada à idade (p<0,001). As calcificações possuem relação com o sexo (p = 0,03) com maior razão de chance de desenvolvimento em homens (odds ratio [OR] = 1,55). O tabagismo (p<0,001), o sedentarismo (p<0,001), a hipertensão arterial sistêmica (p<0,001), o diabetes mellitus (p = 0,04) e as dislipidemias (p<0,001) mostraram associação positiva. Conclusão: A prevalência de achados incidentais de CAC foi de 44%; variam em maior número entre leve e grave; maior razão de chance no sexo masculino e aumento da prevalência com a idade. Portanto, a TC de tórax mostra-se um efetivo método para avaliar as CAC, e juntamente com a história clínica do paciente pode ser utilizada para medir os fatores de risco para doenças cardiovasculares e intervir no desfecho do quadro.(AU)
Introduction: Coronary artery calcifications (CAC) are shown to be a predictive factor of cardiovascular diseases. Computed tomography (CT) of the chest with a low-dose acquisition protocol is accurate in identifying CAC and provides incidental findings of these calcifications, which are commonly overlooked. This study will analyze the prevalence of incidental findings of calcification in coronary arteries in non-cardiac individuals undergoing chest CT. Methods: Consecutive cross-sectional study of an analytical and descriptive nature. Individuals of both genders who underwent chest CT by referral, over 18 years of age and without heart disease were included. Data collection was carried out using medical records and a self-applied anamnesis form. The variables referring to the CAC and the extension of the impairment were obtained from the reassessment of the chest CT images available in the institution's system. The exams were anonymized and evaluated by two experienced radiologists. P≤0.05 was considered statistically significant. Results: 397 exams were analyzed. A prevalence of calcifications was found in 176 (44%) of the cases. The existence of these coronary calcifications is related to age (p<0.001). Calcifications are related to gender (p = 0.03) with a higher odds ratio of development in men (odds ratio [OR] = 1.55). Smoking (p<0.001), sedentary lifestyle (p<0.001), systemic arterial hypertension (p<0.001), Diabetes Mellitus (p = 0.04), and dyslipidemia (p<0.001) showed a positive association. Conclusion: The prevalence of incidental CAC findings was 44%; vary in greater numbers between mild and severe; higher odds ratio in males and increased prevalence with age. Therefore, chest CT proves to be an effective method to assess CAC, and together with the patient's clinical history, it can be used to measure risk factors for CVD and intervene in the outcome of the condition.(AU)
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Humanos , Masculino , Femenino , Adulto , Hallazgos Incidentales , Calcificación Vascular/fisiopatología , Calcificación Vascular/prevención & control , Calcificación Vascular/diagnóstico por imagen , Tabaquismo/etiología , Dolor en el Pecho/etiología , Tomografía Computarizada por Rayos X/métodos , Diabetes Mellitus/etiología , Disnea/etiología , Hemoptisis/etiología , Hipertensión/etiologíaRESUMEN
Traditional Chinese medicine (TCM) has certain advantages in the treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). In recent years, there have been many studies on the treatment of CKD-MBD by Chinese medicinal compounds and monomers. As revealed by literature retrieval, the research on the mechanism of Chinese medicine in intervening in signaling pathways related to CKD-MBD was mainly based on self-made Chinese medicinal compounds, and the action pathways involved fibroblast growth factor 23/Klotho (FGF23/Klotho) signaling pathway, Wnt/β-catenin signaling pathway, receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANK/RANKL/OPG) system, and other signaling pathways. TCM can improve calcium and phosphorus metabolism and bone metabolism disorder, and regulate inflammatory reaction, oxidative stress, apoptosis, and autophagy by regulating this series of signaling pathways for the treatment of CKD-MBD. This paper introduced the research results of these signaling pathways and the mechanism of TCM in the treatment of CKD-MBD in order to provide ideas and references for the related research of Chinese medicine in the treatment of CKD-MBD.
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Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.
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Humanos , Enfermedades Cardiovasculares , Túnica Íntima , Calcificación Vascular , Relevancia Clínica , Neuropatías DiabéticasRESUMEN
Vascular complications are the primary cause of the high disability and mortality in diabetic patients. Vascular calcification is a pathological basis of diabetic vascular complications and increases the risk of adverse cardiovascular events and the difficulty of revascularization in diabetic patients. It is of great clinical value to explore the measures for prevention and treatment of diabetic vascular calcification with integrated traditional Chinese and Western medicine. This paper explores the intrinsic association of stasis, toxin, and deficiency with diabetic vascular calcification to reveal the pathogenesis of diabetic vascular calcification. Stasis and toxin are causally affected by and combined with each other; deficiency refers to the deficiency of healthy Qi and the loss of Qi and blood. The three elements are associated with the occurrence and development of blood vessel diseases. This paper proposes the evolutional law of stasis, toxin, and deficiency in traditional Chinese medicine (TCM) for diabetic vascular calcification. Specifically, diabetic vascular calcification is rooted in the stasis of meridians and collaterals, develops due to the combination of stasis and toxin, and is aggravated by middle Qi deficiency. Furthermore, this paper proposes the TCM intervention principle of activating blood, removing toxin, tonifying deficiency, and dredging collaterals for the prevention and treatment of diabetic vascular calcification. The aim is to provide a theoretical basis for clinical and translational research on the prevention and treatment of diabetic vascular calcification with integrated Chinese and Western medicine.
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Chronic kidney disease (CKD)-mineral and bone disorder (CKD-MBD) is a common complication of CKD, which seriously affects the prognosis of patients. It is a series of abnormal mineral and bone metabolism syndrome caused by chronic renal function decline. The clinical manifestations are mainly decreased or increased serum calcium, increased serum phosphorus, increased intact parathyroid hormone, osteoporosis, and vascular calcification, etc. The paper reviews the research progress in the diagnosis, treatment and management based on the basic and clinical studies of hyperphosphatemia, secondary hyperparathyroidism, renal osteodystrophy and vascular calcification, etc.
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Objective:To improve the understanding of hemodialysis complicated with mesenteric artery calcified stenosis and mesenteric ischemia through the analysis of the case and review of related literature.Methods:A case of hemodialysis with intractable abdominal pain as the main manifestation was reported, and its clinical features, diagnosis and treatment were summarized.Results:The case was a maintenance hemodialysis patient with persistent dull pain around the umbilicus, which worsens after meal and hemodialysis. The results showed multiple vascular calcification, superior mesenteric artery stenosis so the patient was diagnosed with chronic mesenteric ischemia. Mesenteric revascularization under intervention was planned but the guide wire failed to enter the superior mesenteric artery after repeated attempts during the operation. Surgical treatment was recommended, but the patient and family refused surgery and were discharged.Conclusions:Dialysis patients with intractable abdominal pain should be carefully identified and alert for mesenteric artery disease and mesenteric ischemia.
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Objective:To access the clinical value and related risk factors of aortic arch calcification (AoAC) in patients with renal secondary hyperparathyroidism (SHPT) on CT during parathyroid SPECT/CT imaging.Methods:From January 2014 to May 2021, 136 renal SHPT patients (70 males, 66 females, age (50.1±11.4) years) who underwent parathyroid 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT in Affiliated Jiangyin Hospital of Nantong University were retrospectively enrolled. AoAC score was estimated with CT(1-5), and patients were divided into none-light AoAC group (AoAC score<3) and moderate-severe AoAC group (AoAC score≥3). Independent-sample t test or Mann-Whitney U test was used to compare differences of various indicators between two groups. Univariate binary logistic regression was used to analyze the influencing factors of AoAC. Results:Of 136 renal SHPT patients, 111(81.62%) were AoAC detected by CT. There were 84 patients in none-light AoAC group and 52 patients in moderate-severe AoAC group. The age ((46.7±9.8) vs (55.7±11.6) years; t=-4.84, P<0.001), pulse pressure (52(41, 64) vs 60(51, 70) mmHg (1 mmHg=0.133 kPa); z=-3.27, P=0.001), serum corrected calcium (2.41(2.28, 2.53) vs (2.49±0.22) mmol/L; z=-2.50, P=0.013), serum phosphorus ((1.95±0.39) vs (2.14±0.48) mmol/L; t=-2.54, P=0.012), calcium phosphorus product ((4.68±1.07) vs (5.29±1.10) mmol 2/L 2;t=-3.21, P=0.013) and parathyroid hormone (PTH) level (106.30(90.15, 127.45) vs 109.90(87.93, 157.63) pmol/L; z=-2.09, P=0.036) between non-light AoAC group and moderate-severe AoAC group were significantly different. Logistic regression analysis showed that serum phosphorus (odds ratio ( OR)=7.261, 95% CI: 2.416-21.819, P<0.001), calcium and phosphorus product ( OR=1.598, 95% CI: 1.073-2.380, P=0.021) and PTH level ( OR=1.018, 95% CI: 1.007-1.029, P=0.001) were independent risk factors of AoAC. Conclusions:Hybrid SPECT/CT can be used for an effective method of evaluating AoAC in patients with renal SHPT. High serum phosphorus, high calcium phosphorus product and high PTH level may be independent risk factors of AoAC.
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Objective:To evaluate left ventricular structural and functional abnormalities and vascular calcification in kidney transplant (KT) recipients, explore their influencing factors and examine the effects of mineral and bone disorders.Methods:From January 2017 to December 2019, retrospective analysis was performed for 292 KT recipients. Biochemical markers of bone metabolism, bone mineral density (BMD), left ventricular hypertrophy (LVH), left ventricular ejection fraction (LVEF), left ventricular diastolic function, coronary artery calcification (CAC) score and thoracic aortic calcification (TAC) score were assessed. Linear regression and binary Logistic regression analyses were employed for evaluating the influencing factors of cardiovascular parameters and the influence of abnormal mineral and bone metabolism.Results:Postoperative abnormalities in mineral and bone disorders were manifested mostly as hypercalcemia (8.9%, 26/292), hypophosphatemia (27.1%, 79/292), low 25-hydroxyvitamin D (25(OH)vitD) (67.0%, 196/292), hyperparathyroidismhigh parathyroid hormone (PTH) (50.6%, 148/292), elevated bone turnover markers and bone loss rate of 25%-30%. The prevalence of LVH, LVEF<50%, left ventricular diastolic dysfunction, high CAC score and high TAC score were 39.9%(116/292), 0%, 13.1%(38/292), 17.3%(50/292) and 39.9%(116/292) respectively. The results of multivariate analysis indicated that LVH was correlated positively with hypertension and serum calcium (Ca) (95% CI: 1.242-28.080, P=0.026; 95% CI: 1.714-277.584, P=0.018); LVEF was correlated positively with lumbar vertebrae BMD (95% CI: 0.000 1-0.005 5, P=0.041); Left ventricular diastolic dysfunction was correlated positively with age, diabetes and parathyroid hyperplasia/nodules (95% CI: 1.050-1.176, P<0.001; 95% CI: 2.118-43.813, P=0.003 and 95% CI: 1.419-9.103, P=0.007); High CAC score was correlated positively with recipient age and dialysis time (95% CI: 1.036-1.160, P=0.001; 95% CI: 1.009-1.041, P=0.002); High TAC score was correlated positively with age (95% CI: 1.095-1.215, P<0.001). Correlation analysis indicated that TAC was correlated positively with serum Ca ( r=0.233, P=0.003), bone-specific alkaline phosphatase (BALP)( r=0.325, P<0.001) and type Ⅰ collagen cross-linked N-terminal peptide (NTX)( r=0.204, P=0.011) and negatively with femoral neck BMD ( r=0.194, P=0.017). Conclusions:There is a high prevalence of left ventricular structural and functional abnormalities and vascular calcification. It is closely correlated with mineral and bone disorders.
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Objective:To evaluate the extent and progression of coronary artery calcification in maintenance hemodialysis (MHD) patients, and to explore the risk factors of rapid progression of coronary artery calcification in MHD patients.Methods:The patients who underwent MHD in the Huashan Hospital affiliated to Fudan University from January 1, 2013 to December 31, 2017 were enrolled. This study included cross-sectional study and prospective cohort study. Multi-slice spiral computed tomography was used to measure coronary artery calcification, and coronary artery calcium score (CACS) was calculated. In the cross-sectional study, 62 MHD patients were enrolled. According to baseline CACS, the patients were divided into low calcification group (CACS < 100) and high calcification group (CACS ≥ 100). The nutritional and bone mineral metabolism indexes were compared between the two groups. Multiple linear regression analysis was used to analyze the correlation between CACS and muscle mass and laboratory indicators. Since 6 patients were lost to follow-up, 56 MHD patients who were followed-up regularly were enrolled in the prospective cohort study. According to the progression of CACS, the patients were divided into slow progression group (ΔCACS/year < 100) and rapid progression group (ΔCACS/year ≥ 100). Logistic regression equation was used to analyze the risk factors of coronary calcification progression. Hosmer-Lemeshow goodness of fit test and receiver operating characteristic curve were used to evaluate the performance of multivariate logistic regression model.Results:In the cross-sectional study, the age of 62 patients was (62.34±10.82) years old, and the median dialysis age was 78 (39,139) months. Among the 33 male patients, compared with the low calcification group ( n=7), the high calcification group ( n=26) had older age ( t=-2.281, P=0.030) and higher blood triglyceride ( Z=-1.985, P=0.047), and there was no statistically significant difference in muscle mass between the two groups; among the 29 female patients, the muscle mass/height 2 ( t=-2.600, P=0.015) and serum calcium ( t=-2.641, P=0.014) in the high calcification group ( n=15) were both higher than those in the low calcification group ( n=14), and the hemoglobin level was lower ( t=2.531, P=0.018), and the difference in muscle mass between the two groups was not statistically significant. High sensitivity C-reactive protein ( β=0.425, P=0.022) was independently correlated with CACS in male patients, and muscle mass/extracellular water ( β=-0.580, P=0.001) was independently correlated with CACS in female patients. In the prospective cohort study, the age of 56 patients was (59.82±11.14) years old, and the median dialysis age was 82 (40, 146) months. There was no significant difference in all-cause mortality between slow progression group ( n=22) and rapid progression group ( n=34), but the proportion of cardiovascular events in rapid progression group was significantly higher than that in slow progression group ( P=0.017). Compared with the slow progression group, the rapid progression group had higher proportion of males ( χ2=4.791, P=0.029), older age ( Z=-2.131, P=0.038), lower baseline muscle mass/extracellular water ( Z=2.482, P=0.016) and high-density lipoprotein cholesterol ( t=2.133, P=0.042), and faster rate of muscle mass loss (Δmuscle mass·height -2·year -1) ( Z=-2.282, P=0.023). Multivariate logistic regression analysis results showed that muscle mass loss ( OR=0.089, 95% CI 0.010-0.792, P=0.030) and baseline CACS ( OR=1.003, 95% CI 1.000-1.005, P=0.021) were influencing factors for progression of coronary artery calcification in MHD patients. Conclusion:Increasing baseline CACS and rapid reduction in muscle mass are risk factors for the progression of coronary artery calcification in MHD patients.
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Objective:To investigate the role and diagnostic value of miRNA-205 in chronic kidney disease (CKD) patients with vascular calcification.Methods:It was divided into in vitro cell experiment and retrospective cohort study. In vitro experiments were conducted by using rat thoracic aortic smooth muscle cells. Alizarin red staining and calcium content detection were used to detect the calcification of vascular smooth muscle cells (VSMCs). Alkaline phosphatase (ALP) test kit was used to measure ALP activity. Western blotting was used to detect the protein expression levels of osteogenic transcription factors runt-related transcription factor 2 (Runx2), α smooth muscle actin (α-SMA) and smooth muscle-22α (SM-22α) in VSMCs. qRT-PCR was used to detect miRNA-205 and Runx2 expression levels. The double luciferase reporter gene assay was used to verify the targeted relationship between miRNA-205 and Runx2. The non-dialysis patients with CKD 3-5 stage from June 2020 to January 2021 in the Department of Nephrology of Fourth Hospital, Hebei Medical University were selected. According to coronary artery calcium score (CACs), the patients were divided into non-calcification group (CACs=0), mild-moderate calcification group (0<CACs≤400), and severe calcification group (CACs > 400). Spearman correlation analysis was used to analyze the correlation between miRNA-205 and Runx2 and vascular calcification. Logistic regression model and receiver operating characteristic (ROC) curve analysis were used to analyze the ability of miRNA-205 to predict the vascular calcification in patients with CKD. Results:(1)Compared with the control group, calcium nodules were more, and the calcium content, ALP activity and Runx2 protein level were higher, and the expression levels of miRNA-205, α-SMA and SM-22α were significantly lower in high phosphorus group (all P<0.05). Overexpression of miRNA-205 significantly reduced the calcification of VSMCs and Runx2 protein level, and increased the protein levels of α-SMA and SM-22α (all P<0.05). miRNA-205-5p reduced the activity of luciferase in the wild-type Runx2-3'-end non-coding region plasmid. (2) Eighty CKD patients were enrolled, with age of (57.50±14.93) years old and 49 males (61.3%). The results of comparison of miRNA-205 and Runx2 expression levels in non-calcification group ( n=26), mild- moderate calcification group ( n=30) and severe calcification group ( n=24) showed that, the higher degree of calcification, the lower miRNA-205 expression level and the higher Runx2 mRNA expression level (all P<0.05). miRNA-205 was negatively correlated with CACs ( r=-0.50, P<0.01) and Runx2 was positively correlated with CACs ( r=0.55, P<0.01). Multivariate logistic regression analysis results suggested that miRNA-205 ( OR=0.451, 95% CI 0.122-0.873) was an independent influencing factor of vascular calcification in CKD patients. The area under the ROC curve of miRNA-205 and miRNA-205 combined with Runx2 for predicting vascular calcification were 0.796 (95% CI 0.697-0.859) and 0.924 (95% CI 0.866-0.982), respectively. Conclusions:miRNA-205 inhibits vascular calcification by targeting Runx2 to negatively regulate osteogenetic phenotype transformation of VSMCs and is expected to be an early diagnostic marker of vascular calcification in CKD patients.
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Objective:To investigate the role and mechanism of N 6-methyladenosine (m 6A) methyltransferase-like 3 (METTL3) in vascular calcification (VC) of chronic kidney disease (CKD) through apoptosis-associated protein. Methods:(1) Real-time fluorescence quantitative PCR was used to test METTL3 mRNA in serum of maintenance hemodialysis (MHD) patients. (2) Western blotting was used to detect the expression of METTL3 protein in high-phosphorus stimulated vascular smooth muscle cells (VSMCs), and immunofluorescence double lable was used to observe the distribution of METTL3 and Runt-related transcription factor 2 (Runx2). The METTL3 overexpressed and knockdown plasmids were constructed and transfected into VSMCs. Alizarin red staining was used to detect calcification degree. Western blotting was used to detect the expressions of osteogenic markers [Runx2, bone morphogenetic protein-2(BMP-2), collagen Ⅰ] and apoptosis- related proteins Bax and Bcl-2. (3) SD rats were randomly divided into control group, CKD-VC group and S-adenosylhomocysteine (SAH) intervention group. The calcification of thoracic aorta was evaluated by von Kossa staining, and the protein expressions of Runx2, Bax and Bcl-2 were detected by immunohistochemistry and Western blotting.Results:(1) METTL3 mRNA expression in MHD patients with VC was significantly lower than that in non-VC patients ( P<0.05), and was negatively correlated with coronary artery calcium score ( r=-0.65, P<0.001). (2) The expression of METTL3 in VSMCs stimulated by high phosphorus was decreased and showed a time dependence. Immunofluorescence double label showed that METTL3 and Runx2 were co-expressed in the nucleus. METTL3 was overexpressed in high-phosphorus induced VSMCs, and the expressions of Runx2, collagen I and BMP-2 were significantly decreased, accompanied by the decrease of calcified nodules and Bax/Bcl-2 ratio (all P<0.05). Conversely, METTL3 knockdown aggravated VSMCs calcification by inducing apoptosis. (3) Furthermore, METTL3 inhibitor SAH was administered in vivo, and it was found that inhibition of METTL3 expression significantly increased the calcification of rat thoracic aorta, and the Bax/Bcl-2 ratio and Runx2 expression were up-regulated. Conclusions:Serum METTL3 level is reduced in MHD patients with VC. In vivo and in vitro studies demonstrate that METTL3 inhibits VC in CKD by mediating the apoptosis-related protein Bax/Bcl-2.
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Aim To investigate the therapeutic effect of lanthanum hydroxide on renal injury and vascular calcification in rats caused by chronic kidney disease (CKD) and the underlying mechanism. Methods A CKD model was constructed by adenine, and the rats were randomly divided into model group, lanthanum hydroxide low, medium and high dose groups, lanthanum carbonate group and calcium carbonate group. After eight weeks, serum phosphorus ( Pi ), calcium (Ca), serum creatinine ( Scr), blood urea nitrogen ( BUN ), parathyroid hormone ( PTH ), fibroblast growth factor 23 ( FGF23 ) and tartrate-resistant acid phosphatase 5b ( TARP-5b) levels were measured. Histopathological staining was used to assess the degree of calcification of blood vessels, and the expressions of smooth muscle protein 22α ( SM22α), Runt-related transcription factor 2 ( RUNX2 ), hypoxia inducible factor 1 ( HIF-1) pathway mRNA and protein expression in blood vessels were detected. Results Lanthanum hydroxide can significantly reduce the levels of Pi, Scr, BUN, PTH, FGF23 and TARP-5b in the serum of CKD rats, significantly reduce the calcium deposition of the thoracic aorta of CKD rats, the expression of BMP-2, VEGF in the cytoplasm, the expression of RUNX2, HIF-1α in the nucleus, and increase the mRNA and protein expression of SM22. Conclusion Lanthanum hydroxide can markedly improve hyperphosphatemia in CKD rats, and can improve vascular calcification in CKD rats by blocking HIF-1α signaling pathway.