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1.
Chinese journal of integrative medicine ; (12): 277-288, 2024.
Article in English | WPRIM | ID: wpr-1010331

ABSTRACT

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.


Subject(s)
Humans , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Medicine, Chinese Traditional , Atherosclerosis/drug therapy , Lipoproteins , Plaque, Atherosclerotic , Biomarkers
2.
Educ. med. super ; 37(2)jun. 2023. tab
Article in Spanish | LILACS, CUMED | ID: biblio-1528530

ABSTRACT

Introducción: La satisfacción de los estudiantes con respecto a la educación que reciben es un elemento clave en la valoración de la calidad de la educación. La enfermedad causada por el nuevo coronavirus SARS-CoV-2 representó una emergencia sanitaria que generó preocupación a nivel mundial por su impacto en la salud, la economía y la educación. Objetivo: Evaluar la satisfacción de los estudiantes con los cursos a distancia del primer ciclo de la maestría Investigación en Aterosclerosis durante la COVID-19. Métodos: Se hizo un estudio descriptivo de corte transversal. Se utilizó una encuesta, que estuvo disponible, al finalizar cada curso, en el Aula Virtual de Salud. Los datos de la encuesta se obtuvieron del AVS, se introdujeron en una base de datos en Excel, y se procesaron con el paquete estadístico SPSS versión 20.0 para Windows. Resultados: Para todos los cursos los horarios que predominaron fueron en horario extralaboral y los fines de semana y durante la jornada laboral, en horario extralaboral y los fines de semana. Como vías de conexión más utilizadas estuvieron Infomed y los datos móviles. El curso mejor orientado resultó La aterosclerosis, un problema epidemiológico. La evaluación de los aspectos relacionados con el profesor, los contenidos, el material bibliográfico, la comunicación y el aseguramiento tecnológico fue satisfactoria. La computadora y el celular representaron los dispositivos tecnológicos más empleados. Las respuestas en relación con la satisfacción con los cursos se encontraron entre satisfecho y muy satisfecho. Conclusiones: La mayor parte de los aspectos evaluados recibieron calificaciones satisfactorias. Como aspecto positivo se destaca el empleo del aula virtual; como negativos, la dificultad con los dispositivos tecnológicos y la conectividad; y como interesantes, la adquisición y el perfeccionamiento de habilidades con los cursos a distancia y mejorar la calidad de la conectividad(AU)


Introduction: Student satisfaction with the education that they receive is a key element for education quality assessment. The disease caused by the new SARS-CoV-2 coronavirus represented a health emergency that generated worldwide concern due to its impact on health, economy and education. Objective: To assess student satisfaction with the distance courses of the first cycle of a master's degree in atherosclerosis research during COVID-19. Methods: A descriptive and cross-sectional study was carried out. A survey was used, available in the virtual health classroom at the end of each course. The survey's data were obtained from the virtual health classroom, entered into an Excel database, and processed with the statistical package SPSS (version 20.0) for Windows. Results: For all the courses, the predominant schedules were during out-of-work hours and on weekends and during the working day, during out-of-work hours and on weekends. The most frequently used means of connection were Infomed and mobile data. The best oriented course was Atherosclerosis, an epidemiological problem. The assessment of aspects related to the professor, the contents, the bibliographic material, communication and technological assurance were satisfactory. The computer and the cell phone were the most frequently used technological devices. The responses regarding satisfaction with the courses ranged between satisfied and very satisfied. Conclusions: Most of the assessed aspects received satisfactory ratings. As a positive aspect, the use of the virtual classroom stands out; as a negative one, the difficulty with technological devices and connectivity; and as interesting ones, the acquisition and improvement of skills with distance courses, as well as improving the quality of connectivity(AU)


Subject(s)
Humans , Education, Distance/methods , Training Courses , Atherosclerosis , Research/education , Epidemiology, Descriptive , Cross-Sectional Studies , COVID-19/prevention & control
3.
Medisan ; 27(1)feb. 2023. tab,graf
Article in Spanish | LILACS, CUMED | ID: biblio-1440564

ABSTRACT

Introducción: Las enfermedades cardiovasculares constituyen la primera causa de muerte en Cuba y el mundo. Objetivo: Identificar los factores predictivos de defunciones por enfermedad cardiovascular aterosclerótica en personas de edad avanzada. Métodos: Se realizó un estudio analítico, de tipo caso-control, que incluyó a 237 pacientes fallecidos a causa de cardiopatía ateroesclerótica (casos) y 711 ancianos vivos (controles), pertenecientes a 3 áreas de salud del municipio de Santiago de Cuba, desde enero hasta diciembre de 2021. Resultados: Los factores predictivos que formaron parte del modelo fueron el tabaquismo, la dieta poco saludable, el sedentarismo, la diabetes mellitus, la enfermedad renal crónica, la fragilidad, el deterioro cognitivo y la multimorbilidad. Conclusiones: Los factores de riesgo tradicionales seleccionados en este estudio, combinados con otras condiciones potenciales, mejoraron la predicción de la mortalidad por cardiopatías en ancianos y facilitaron la orientación de las intervenciones preventivas en este grupo poblacional.


Introduction: Cardiovascular diseases constitute the first death cause in Cuba and the world. Objective: To identify the predictive factors of deaths due to atherosclerotic cardiovascular disease in elderly people. Methods: An analytic case-control type study was carried out that included 237 dead patients due to atherosclerotic heart disease (cases) and 711 living elderly (control), belonging to 3 health areas of Santiago de Cuba municipality, from January to December, 2021. Results: The predictive factors that were part of the model were nicotine addiction, not very healthy diet, physical inactivity, diabetes mellitus, chronic renal disease, fragility, cognitive deterioration and multimorbidity. Conclusions: The traditional risk factors selected in this study, combined with other potential conditions, improved the prediction of mortality due to heart disease in elderly and facilitated the orientation of preventive interventions in this population group.


Subject(s)
Atherosclerosis
4.
The Nigerian Health Journal ; 23(1): 478-488, 2023. tables
Article in English | AIM | ID: biblio-1425502

ABSTRACT

Background: Early-onset atherosclerosis is a marker of future cardiovascular diseases. However, indicators of early dyslipidemia for primary prevention are generally lacking in sub-Saharan Africa. This study aimed at describing the cord blood lipid profile among apparently healthy newborns in a tertiary hospital in Southeast Nigeria, and its relationship with gestational age and birth weight.Methods: Cross-sectional study of 167 consecutively recruited apparently well newborns in a tertiary hospital whose cord blood lipid profile parameters (total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL ­C), low-density lipoprotein cholesterol (LDL ­C) and very low-density lipoprotein cholesterol (VLDL ­C)) were assessed using an autoanalyzer (BiOLis 24i). Lipid variables were presented with descriptive statistics whereas their relationship with gestational age and birth weight was highlighted using Spearman's rank correlation analysis. Dunnett's T3 Post Hoc analysis was used for pairwise comparisons.Results: The 167 newborns recruited included 15 (9%) moderate preterm, 46 (27.5%) late preterm and 106 (63.5%) term babies of which 79 (47.3%) were males and 88 (52.7%) were females. The number of recruited SGA, AGA and LGA were respectively 13 (7.8%), 142 (85%), 12 (7.2%). Mode of delivery was majorly vaginal delivery (69.5%) while the rest (30.5%) was by caesarean section. The median values (in mg/dL) of TC, TG, HDL ­C, LDL ­C and VLDL ­C were 60.0, 30.5, 29.0, 25.8 and 6.1 respectively, all within the normal international ranges. Triglycerides and VLDL-C had a moderate positive correlation with gestational age (rs = 0.4;p < 0.001) and were significantly higher in small-for-gestational-age newborns. Total cholesterol, HDL ­C, and LDL-C had a weak negative correlation with gestational age and birth weight (spearman rs˂-0.3). Birth weight, gestational age, and paternal age were the common predictors of lipid profile variability.Conclusion: The finding of a significant relationship between lipid variables with gestational age and birth weight underscores the need to clinically interpret these given the relationship. The relationship with paternal age is another interesting finding which needs to be replicated and the mechanism(s) elucidated.


Subject(s)
Birth Weight , Fetal Blood , Gestational Age , Atherosclerosis
5.
São Paulo; s.n; s.n; 2023. 83 p. tab, graf.
Thesis in English | LILACS | ID: biblio-1437610

ABSTRACT

Cardiovascular diseases involve hyperlipidemia, inflammation and oxidative stress. Although this relationship is well established, only biomarkers associated with hyperlipidemia and inflammation are currently in clinical practice for diagnosis and evaluation of patient treatment. Our hypothesis is that oxidative stress biomarkers may be an independent risk factor and may assist in cardiovascular risk stratification and contribute to improving current scores. Thus, the objective of this study was to investigate which are the biomarkers and methodologies were used in clinical studies in humans with different health conditions. With the results obtained in the first part, we selected studies conducted in healthy individuals and in individuals under primary and secondary cardiovascular prevention in order to evaluate the most frequent biomarkers, the results obtained according to the individual's profile and the methodology used, and correlate with different health conditions. We observed that malondialdehyde (MDA) was the most frequent lipid biomarker of oxidative stress applied in the studies, but it presented significant variability in the results and a weak correlation with clinical outcomes. The result of this study demonstrates the importance of carrying out a multicentric study to validate the MDA values in individuals with different health conditions and the standardization of the methodology based on high performance liquid chromatographyy (HPLC)


As doenças cardiovasculares envolvem hiperlipidemia, inflamação e estresse oxidativo. Embora essa relação esteja bem estabelecida, apenas biomarcadores associados à hiperlipidemia e inflamação são atuais na prática clínica para diagnóstico e avaliação do tratamento do paciente. Nossa hipótese é que biomarcadores de estresse oxidativo podem ser um fator de risco independente e podem auxiliar na estratificação de risco cardiovascular e contribuir para melhorar os escores atuais. Assim, o objetivo deste estudo foi investigar primeiramente quais são os biomarcadores e metodologias utilizados nos estudos clínicos em humanos em diferentes condições de saúde. Com os resultados obtidos na primeira etapa, selecionamos os estudos conduzidos em indivíduos saudáveis e em prevenção cardiovascular primária e secundária a fim de avaliar os biomarcadores mais utilizados, os resultados obtidos conforme o perfil do indivíduo e a metodologia utilizada e finalmente correlacionar com as diferentes condições de saúde. Observamos que o malondialdeído (MDA) foi o biomarcador lipídico de estresse oxidativo mais frequente nos estudos, porém apresentou importante variabilidade nos resultados e fraca correlação com desfechos clínicos. O resultado desse estudo demonstra a importância da realização de um estudo multicentrico para validação dos valores de MDA nos diferentes perfis de indivíduos e a padronização metodológica baseada na cromatografia líquida de alta eficiência (HPLC)


Subject(s)
Biomarkers/analysis , Oxidative Stress , Patients/classification , Chromatography, High Pressure Liquid/methods , Atherosclerosis/pathology
6.
Chinese Journal of Cardiology ; (12): 642-647, 2023.
Article in Chinese | WPRIM | ID: wpr-984697

ABSTRACT

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.


Subject(s)
Humans , Atrial Fibrillation/drug therapy , Cardiovascular Diseases , Cholesterol, LDL , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Atherosclerosis , Dyslipidemias/drug therapy
7.
Chinese journal of integrative medicine ; (12): 1121-1132, 2023.
Article in English | WPRIM | ID: wpr-1010316

ABSTRACT

OBJECTIVE@#To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS).@*METHODS@#Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot.@*RESULTS@#Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05).@*CONCLUSION@#Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.


Subject(s)
Mice , Animals , Apelin , Tissue Plasminogen Activator/metabolism , Quercetin/therapeutic use , AMP-Activated Protein Kinases/metabolism , Sirtuin 1/metabolism , Signal Transduction/physiology , Atherosclerosis/metabolism , Apolipoproteins E
8.
Frontiers of Medicine ; (4): 317-329, 2023.
Article in English | WPRIM | ID: wpr-982568

ABSTRACT

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.


Subject(s)
Humans , Atherosclerosis/genetics , Autophagy/genetics , Cell Cycle Proteins/metabolism , Endothelial Cells/metabolism , Endothelium/metabolism , MicroRNAs/metabolism , Repressor Proteins/metabolism , RNA Splicing Factors , Serine-Arginine Splicing Factors/genetics , RNA, Long Noncoding/metabolism
9.
International Journal of Oral Science ; (4): 26-26, 2023.
Article in English | WPRIM | ID: wpr-982483

ABSTRACT

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.


Subject(s)
Animals , Mice , Endothelial Cells , Toll-Like Receptor 2 , Macrophages , Apoptosis , Atherosclerosis , Myocytes, Smooth Muscle , MicroRNAs
10.
Chinese journal of integrative medicine ; (12): 179-185, 2023.
Article in English | WPRIM | ID: wpr-971334

ABSTRACT

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.


Subject(s)
Humans , Atherosclerosis , Scavenger Receptors, Class E/physiology , Biomarkers , Plant Extracts , Lipoproteins, LDL
11.
China Journal of Chinese Materia Medica ; (24): 1431-1437, 2023.
Article in Chinese | WPRIM | ID: wpr-970614

ABSTRACT

Atherosclerosis(AS) is the key pathological basis of coronary heart disease(CHD), and lipid infiltration is a classical theory to explain the pathological mechanism of AS. The theory highlights that the occurrence and development of AS are closely related to abnormal lipid metabolism, with the essence of the pathological reaction caused by the invasion of lipids into arterial intima from plasma. Phlegm and blood stasis are physiologically homologous and subject to pathological co-existence. Phlegm-blood stasis correlation is the basic theory to explain the pathogenesis characteristics of CHD and has important guiding significance for revealing the mecha-nism of lipid infiltration of CHD. Phlegm is the pathological product of abnormal metabolism of Qi, blood, and body fluid, and a gene-ral summary of a series of abnormally expressed lipid substances. Among them, turbid phlegm invades the heart vessels, gradually accumulates, and condenses to achieve the qualitative change from "invisible pathogen" to "tangible pathogen", which corresponds to the mechanism of lipid migration and deposition in the intima of blood vessels, and is the starting factor of the disease. Blood stasis is the continuous development of phlegm, and it is a result of pathological states such as decreased blood fluidity, increased blood coagulation, and abnormal rheology. The fact that blood stasis caused by phlegm accords with the pathological process of "lipid abnormality-circulatory disturbance" and is the central link of the disease. Phlegm and blood stasis aggravate each other and lead to indissoluble cementation. The phlegm-blood stasis combination serves as common pathogen to trigger the disease, which is the inevitable outcome of the disease. Based on the phlegm-blood stasis correlation theory, the simultaneous treatment of phlegm and blood stasis is established. It is found that this therapy can simultaneously regulate blood lipid, reduce blood viscosity, and improve blood circulation, which can fundamentally cut off the biological material basis of the reciprocal transformation between phlegm and blood stasis, thus exerting a significant curative effect.


Subject(s)
Humans , Medicine, Chinese Traditional , Coronary Disease , Mucus , Atherosclerosis , Lipids
12.
China Journal of Chinese Materia Medica ; (24): 1352-1369, 2023.
Article in Chinese | WPRIM | ID: wpr-970606

ABSTRACT

Atherosclerosis(AS) is caused by impaired lipid metabolism, which deposits lipids in the intima, causes vascular fibrosis and calcification, and then leads to stiffening of the vascular wall. Hyperlipidemia(HLP) is one of the key risk factors for AS. Based on the theory of "nutrients return to the heart and fat accumulates in the channels", it is believed that the excess fat returning to the heart in the vessels is the key pathogenic factor of AS. The accumulation of fat in the vessels over time and the blood stasis are the pathological mechanisms leading to the development of HLP and AS, and "turbid phlegm and fat" and "blood stasis" are the pathological products of the progression of HLP into AS. Didang Decoction(DDD) is a potent prescription effective in activating blood circulation, removing blood stasis, resolving turbidity, lowering lipids, and dredging blood vessels, with the functions of dispelling stasis to promote regeneration, which has certain effects in the treatment of atherosclerotic diseases. This study employed high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) to screen the main blood components of DDD, explored the targets and mechanisms of DDD against AS and HLP with network pharmacology, and verified the network pharmacological results by in vitro experiments. A total of 231 blood components of DDD were obtained, including 157 compounds with a composite score >60. There were 903 predicted targets obtained from SwissTargetPrediction and 279 disease targets from GeneCards, OMIM, and DisGeNET, and 79 potential target genes of DDD against AS and HLP were obtained by intersection. Gene Ontology(GO) analysis suggested that DDD presumably exerted regulation through biological processes such as cholesterol metabolism and inflammatory response, and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis suggested that signaling pathways included lipid and atherosclerosis, insulin resistance, chemo-carcinogenesis-receptor activation, and AGE-RAGE signaling pathways in diabetic complications. In vitro experiments showed that DDD could reduce free fatty acid-induced lipid accumulation and cholesterol ester content in L02 cells and improve cellular activity, which might be related to the up-regulation of the expression of PPARα, LPL, PPARG, VEGFA, CETP, CYP1A1, and CYP3A4, and the down-regulation of the expression of TNF-α and IL-6. DDD may play a role in preventing and treating AS and HLP by improving lipid metabolism and inflammatory response, and inhibiting apoptosis with multi-component, multi-target, and multi-pathway characteristics.


Subject(s)
Humans , Hyperlipidemias/drug therapy , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid , Network Pharmacology , Nutrients , Atherosclerosis/prevention & control , Lipids , Drugs, Chinese Herbal/pharmacology , Molecular Docking Simulation
13.
China Journal of Chinese Materia Medica ; (24): 234-246, 2023.
Article in Chinese | WPRIM | ID: wpr-970519

ABSTRACT

This study aimed to evaluate the efficacy and safety of Chinese patent medicines containing Hirudo in the treatment of atherosclerosis(AS) by network Meta-analysis, and to provide evidence-based reference for clinical treatment of AS. The clinical randomized controlled trial(RCT) on the treatment of atherosclerosis with Chinese patent medicines containing Hirudo were searched in CNKI, Wanfang, VIP, SinoMed, PubMed and EMbase from the establishment of the databases to July 1, 2022. And data extraction and quality assessment of the included RCT was performed according to the Cochrane standards. Stata 17 and ADDIS 1.16.5 were then used for Bayesian model network Meta-analysis. Finally, 67 RCTs with a total sample size of 6 826 cases were included, 3 569 cases in the experimental group and 3 257 cases in the control group, involving three oral Chinese patent medicines. Network Meta-analysis showed that in terms of reducing intima-media thickness(IMT), the top three Chinese patent medicines were Tongxinluo Capsules+sta-tins>Maixuekang Capsules+statins>Maixuekang Capsules. In terms of reducing plaque area, the top one was Maixuekang Capsules+sta-tins, and the other Chinese patent medicines had similar efficacy. For lowering AS Crouse scores, the top three were Maixuekang Capsules>Tongxinluo Capsules+statins>Naoxintong Capsules. For decreasing plaque number, the top three were Naoxintong Capsules+sta-tins>Tongxinluo Capsules+statins>Tongxinluo Capsules. With regard to adverse reactions/events, Naoxintong Capsules+statins had the lo-west incidence. In conclusion, in Chinese patent medicines containing Hirudo for the treatment of AS, Tongxinluo Capsules+statins, Maixuekang Capsules, Maixuekang Capsules+statins, and Naoxintong Capsules+statins were the primary choices to reduce IMT, AS Crouse scores, plaque area, and plaque number, respectively. The efficacy of Chinese patent medicines containing Hirudo with or without statins was more significant than that of statins alone in the four outcome indexes. Additionally, the treatment of AS should be evaluated comprehensively, and attention should be paid to Chinese patent medicines or their combination with western medicine, to optimize the treatment effect and minimize adverse reactions as the benchmark.


Subject(s)
Humans , Network Meta-Analysis , Nonprescription Drugs/therapeutic use , Capsules , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Bayes Theorem , Carotid Intima-Media Thickness , Drugs, Chinese Herbal/therapeutic use , Atherosclerosis/drug therapy , Medicine, Chinese Traditional
14.
China Journal of Chinese Materia Medica ; (24): 202-210, 2023.
Article in Chinese | WPRIM | ID: wpr-970515

ABSTRACT

This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 μg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P<0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 μg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.


Subject(s)
Mice , Animals , NF-kappa B/metabolism , NF-KappaB Inhibitor alpha/metabolism , Tumor Necrosis Factor-alpha/metabolism , Glycosides/pharmacology , Cholesterol, LDL , Atherosclerosis/genetics , Signal Transduction , Inflammation/drug therapy , Interleukin-6 , Apolipoproteins E/pharmacology , RNA, Messenger/metabolism
15.
China Journal of Chinese Materia Medica ; (24): 465-471, 2023.
Article in Chinese | WPRIM | ID: wpr-970483

ABSTRACT

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.


Subject(s)
Animals , Mice , Apolipoproteins E , Atherosclerosis/genetics , Beclin-1 , Cholesterol, LDL , Intercellular Adhesion Molecule-1 , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases/metabolism , Plaque, Atherosclerotic , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/genetics , Vascular Cell Adhesion Molecule-1/genetics
16.
China Journal of Chinese Materia Medica ; (24): 311-320, 2023.
Article in Chinese | WPRIM | ID: wpr-970467

ABSTRACT

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.


Subject(s)
Humans , Endothelial Cells/metabolism , Cardiovascular Diseases , Medicine, Chinese Traditional , Atherosclerosis/prevention & control , Lipoproteins, LDL/metabolism , Endothelium, Vascular , Plaque, Atherosclerotic , Autophagy
17.
Acta Academiae Medicinae Sinicae ; (6): 38-43, 2023.
Article in Chinese | WPRIM | ID: wpr-970444

ABSTRACT

Objective To explore the risk factors of clopidogrel resistance (CR) in the elderly patients with atherosclerotic cardiovascular disease and to provide evidence for the antiplatelet therapy. Methods A total of 223 elderly patients (≥80 years old) with atherosclerotic cardiovascular disease treated in the Department of Geriatrics in the Peking University People's Hospital from January 18,2013 to November 30,2019 and meeting the inclusion criteria were enrolled in this study.The clinical data and laboratory test results were collected,including clinical disease,drug use,physical examination,complete blood cell analysis,biochemical indicators,and thromboelastogram (TEG).The rate of platelet inhibition induced by adenosine diphosphate was calculated according to the TEG.We assigned the patients into a CR group (n=84) and a control group (n=139) to analyze the incidence and influence factors of CR in the elderly patients with atherosclerotic cardiovascular disease. Results The incidence of CR was 37.7% in the elderly patients with atherosclerotic cardiovascular disease.The CR group had lower hemoglobin (t=3.533,P=0.001) and higher hypertension prevalence rate (χ2=6.581,P=0.006),proportion of multiple drugs (χ2=3.332,P=0.048),body mass index (BMI) (t=-2.181,P=0.030),total cholesterol (t=-2.264,P=0.025),triglycerides (Z=-2.937,P=0.003),low-density lipoprotein cholesterol (LDL-C) (t=-2.347,P=0.020),and proportion of women (χ2=5.562,P=0.014) than the control group.The results of multivariate Logistic regression showed that hemoglobin (OR=0.962,P<0.001),BMI (OR=1.154,P=0.003),and LDL-C (OR=1.688,P=0.018) were the factors influencing CR in the elderly patients with atherosclerotic cardiovascular disease. Conclusion Hemoglobin,BMI,and LDL-C may be independent factors associated with the occurrence of CR in the elderly patients with atherosclerotic cardiovascular disease.


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Atherosclerosis , Cardiovascular Diseases , Cholesterol, LDL , Clopidogrel/therapeutic use , Risk Factors
18.
Chinese Journal of Cardiology ; (12): 288-295, 2023.
Article in Chinese | WPRIM | ID: wpr-969776

ABSTRACT

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.


Subject(s)
Rats , Mice , Animals , Rosuvastatin Calcium/therapeutic use , Vascular Endothelial Growth Factor C , Endothelial Cells/metabolism , Atherosclerosis/drug therapy , Plaque, Atherosclerotic , Cholesterol, HDL , Lymphatic System/metabolism
19.
China Journal of Chinese Materia Medica ; (24): 5216-5234, 2023.
Article in Chinese | WPRIM | ID: wpr-1008719

ABSTRACT

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.


Subject(s)
Humans , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Molecular Docking Simulation , Network Pharmacology , Drugs, Chinese Herbal/pharmacology , Capsules , Atherosclerosis , Cerebral Infarction , Neoplasms
20.
China Journal of Chinese Materia Medica ; (24): 4164-4172, 2023.
Article in Chinese | WPRIM | ID: wpr-1008613

ABSTRACT

The study aims to observe the effects and explore the mechanisms of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination in the treatment of the inflammatory response of mice with atherosclerosis(AS) via the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway. Male ApoE~(-/-) mice were randomly assigned into a model group, a Buyang Huanwu Decoction group, an Astragali Radix-Angelicae Sinensis Radix combination group, and an atorvastatin group, and male C57BL/6J mice of the same weeks old were used as the control group. Other groups except the control group were given high-fat diets for 12 weeks to establish the AS model, and drugs were administrated by gavage. Aortic intimal hyperplasia thickness, blood lipid level, plasma inflammatory cytokine levels, M1/M2 macrophage markers, and expression levels of proteins in TLR4/MyD88/NF-κB pathway in the vessel wall were measured to evaluate the effects of drugs on AS lesions and inflammatory responses. The results showed that the AS model was successfully established with the ApoE~(-/-) mice fed with high-fat diets. Compared with the control group, the model group showed elevated plasma total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c) levels(P<0.05), thickened intima(P<0.01), and increased plasma tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels(P<0.01). Moreover, the model group showed increased expression of vascular cell adhesion molecule-1(VCAM-1) and inducible nitric oxide synthase(iNOS)(P<0.01), inhibited expression of endothelial nitric oxide synthase(eNOS) and cluster of differentiation 206(CD206)(P<0.01), and up-regulated mRNA and protein levels of TLR4, MyD88, NF-κB inhibitor alpha(IκBα), and NF-κB in the vessel wall(P<0.05). Compared with the model group, Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination lowered the plasma TC and LDL-c levels(P<0.01), alleviated the intimal hyperplasia(P<0.01), and reduced the plasma TNF-α and IL-6 levels(P<0.05). Moreover, the two interventions promoted the expression of eNOS and CD206(P<0.05), inhibited the expression of VCAM-1 and iNOS(P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, IκBα, and NF-κB(P<0.05) in the vessel wall. This study indicated that Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination could delay the progression of AS, inhibit the polarization of vascular wall macrophages toward M1 type, and attenuate vascular inflammatory response by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway in the vascular wall. Astragali Radix and Angelicae Sinensis Radix were the main pharmacological substances in Buyang Huanwu Decoction for alleviating the AS vascular inflammatory response.


Subject(s)
Mice , Male , Animals , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , NF-KappaB Inhibitor alpha/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Myeloid Differentiation Factor 88/metabolism , Vascular Cell Adhesion Molecule-1/metabolism , Cholesterol, LDL , Hyperplasia , Mice, Inbred C57BL , Atherosclerosis/genetics , Apolipoproteins E/therapeutic use , RNA, Messenger
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