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Objective:To explore the role of SUMOylaiton of peroxisome proliferator-activated receptor γ (PPARγ) in diabetes mellitus prompted inflammation and atherosclerosis in vascular and endothelial cells.Methods:From September 2014 to January 2017, 32 Sprague-Dawley rats in 14 weeks-old were divided into sham operated group, artery injured without diabetes group, artery injured with diabetes group and ubiquitin-conjugating enzyme 9 (UBC9) transfection group (Group D) by random digits table method with 8 rats each. Model of type 1 diabetes mellitus (T1DM) and rat carotid artery balloon injury was made in the assigned group. One rat was excluded because of model failure in each group. Systolic and diastolic common carotid artery diameter and intimal thickness of injured and healthy common carotid artery were evaluated by vascular ultrasound, and the standardized common carotid artery diastolic diameter (sCADD) was calculated. Histological tests and immunohistochemical staining were performed to evaluate intimal hyperplasia, and the ratio of intimal area to media area was calculated when the media area was equal. Human umbilical vein endothelial cells (HUVEC) were cultured 24 h in high glucose medium with different duration and concentration, and the expression levels of interleukin (IL)-8 and IL-1β mRNA were determined by real time reverse transcription polymerase chain reaction (RT-PCR), the expression level of UBC9 was determined by Western blot method, SUMOylation assay kit was used to evaluate SUMOylation of PPARγ. HUVEC was cultured in vitro and PPAR was stimulated by high glucose at different concentrations and different times PPARγ SUMOylation level. UBC9 was overexpressed by lentivirus in vivo and in vitro, and the PPARγ SUMOylation level was detected.Results:The intimal thickness, intimal area and ratio of intimal area to media area 8 weeks after carotid artery injuring in sham operated group, artery injured without diabetes group and artery injured with diabetes group were increased respectively: (0.026 ± 0.018), (0.084 ± 0.007) and (0.264 ± 0.022) mm; (0.18 ± 0.09) × 10 6, (0.32 ± 0.06) × 10 6 and (1.64 ± 0.22)×10 6 μm 2; 0.345 ± 0.073, 0.570 ± 0.080 and 2.710 ± 0.220, the sCADD was decreased respectively: 0.903 ± 0.084, 0.800 ± 0.071 and 0.330 ± 0.036, and there were statistical differences ( F = 10.40, 9.40, 8.20 and 8.60; P<0.05). After HUVEC was cultured in high glucose for 24 h, the IL-8 mRNA at sugar concentrations of 10, 20 and 40 mmol/L was 1.00 ± 0.11, 3.57 ± 0.22 and 4.07 ± 0.40, the IL-1β mRNA was 1.00 ± 0.07, 3.32 ± 0.29 and 5.13 ± 0.19, and there were statistical differences ( F = 73.05 and 205.80, P<0.05). The level of PPARγ SUMOylation and UBC9 in artery injured with diabetes group were significantly lower than those in artery injured without diabetes group (0.46 ± 0.25 vs. 1.00 ± 0.21 and 0.45 ± 0.02 vs. 1.00 ± 0.07), and there were statistical differences ( P<0.05); there was no statistical difference in PPARγ between 2 groups (0.94 ± 0.07 vs. 1.00 ± 0.04, P>0.05). The UBC9 and PPARγ SUMOylation at sugar concentrations of 0, 10, 20 and 40 mmol/L were decreased respectively (0.99 ± 0.05, 0.80 ± 0.06 and 0.62 ± 0.05; 1.00 ± 0.05, 0.57 ± 0.13 and 0.55 ± 0.08), and there were statistical differences ( F = 21.02 and 14.31, P<0.05); there was no statistical difference in PPARγ (1.00 ± 0.03, 0.90 ± 0.04 and 0.91 ± 0.05; F = 3.11, P>0.05). In HUVEC cultured in high glucose medium (20 mmol/L) for 6, 12, 24 and 48 h, the UBC9 and PPARγ SUMOylation were downregulated progressively (1.00 ± 0.09, 0.75 ± 0.05, 0.70 ± 0.08, 0.38 ± 0.04 and 0.35 ± 0.03; 1.00 ± 0.03, 0.86 ± 0.01, 0.59 ± 0.01, 0.51 ± 0.11 and 0.35 ± 0.08), and there were statistical differences ( F = 36.06 and 33.13, P<0.05); but there was no statistical difference in PPARγ (1.00 ± 0.03, 1.14 ± 0.02, 1.18 ± 0.17, 0.98 ± 0.01 and 1.04 ± 0.05; F = 1.90, P>0.05). After overexpression of UBC9 in rats with diabetes, histological analysis showed that UBC9 in artery injured without diabetes group, artery injured with diabetes group and UBC9 transfection group was 1.53 ± 0.18, 1.00 ± 0.22 and 3.62 ± 0.35, there was statistical difference ( F = 5.64, P<0.05). Ultrasonic test results show that in artery injured without diabetes group, artery injured with diabetes group and UBC9 transfection group intimal thickness was increased respectively: (0.077 ± 0.015), (0.216 ± 0.007) and (0.125 ± 0.014) mm, and there was statistical difference ( F = 27.18, P<0.05). Histological analysis showed that intimal area in artery injured without diabetes group, artery injured with diabetes group and UBC9 transfection group was (0.335 ± 0.066) ×10 6, (1.053 ± 0.103) ×10 6 and (0.544 ± 0.040) ×10 6 μm 2, the ratio of intimal area to media area was 0.63 ± 0.063, 2.03 ± 0.052 and 0.93 ± 0.100, there were statistical differences ( F = 13.58 and 53.96, P<0.05). Conclusions:Diabetes mellitus could inhibit the PPARγ SUMOylaiton and prompt inflammation and atherosclerosis in vascular and endothelial cells. Upregulation of PPARγ SUMOylaiton though UBC9 overexpressioncould play a protecting role in diabetes mellitus prompted atherosclerosis.
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Objective:To study the effects of conservative treatment versus percutaneous interventional treatment(PCI)on symptoms and prognosis of chronic coronary syndrome patients aged over 75 years with fractional flow reserve(FFR)in the grey zone(0.75≤FFR≤0.80).Methods:A total of 96 coronary heart disease(CHD)patients aged over 75 years undergone FFR examination in our hospital from January 2011 to December 2017 were retrospectively selected.All patients showed stenosis of 50%-90% in at least one main coronary artery and had FFR values within the range of 0.75-0.80(0.75≤FFR≤0.80). According to the treatment, patients were divided into the optimized medication group(OMT group, n=35)and the PCI group(n=61). The degree of angina alleviation assessed by the Seattle Angina Questionnaire(SAQ)and the incidence of major adverse cardiovascular endpoints(death, myocardial infarction, stroke, and repeated revascularization)were recorded during the one-year follow-up after treatment.Results:There was no significant difference in baseline data including age, gender and comorbidities between the OMT and PCI groups( P>0.05). The incidence of previous myocardial infarction, and the basal level of low-density lipoprotein cholesterol(LDL-C)were higher in the PCI group than in the OMT group( P<0.05). One-year follow-up showed that there was no significant difference between the OMT and PCI groups in the score of SAQ(77.6 ± 19.5 vs. 83.1 ± 22.8, P>0.05)and the incidence of composite MACEs(11.4% or 4 / 35 vs. 9.8% or 6/61, P>0.05). However, the incidence of repeated target vessel revascularization was lower in the PCI group than in the OMT group(1.6% or 1 case vs. 5.8% or 2 cases, P<0.05). Conclusions:In elderly CHD patients aged over 75 years with FFR values between 0.75-0.8 in the grey zone, optimal medication treatment has similar effects as the PCI on symptom alleviation, and no significant increase in composite MACEs is found at one-year follow-up.
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Coronary atherosclerosis (CAS) has been recognized as a chronic inflammatory disease in recent years.As an important component of innate immunity,complement system plays an important role in the pathogenesis of CAS.Multiple components of plaque can activate complement proteins,and the activation of complement promotes the progression of plaque lesions in turn.However,recent studies have also found that some proteins of the complement system may also paly an atheroprotective role in the early stage of atherosclerosis.In addition to the direct effects,complement system is also involved in CAS-related pathological changes.Complement proteins may be promising biomarkers,as confirmed by clinical studies which suggest that circulation levels of some complement proteins can predict the risk and prognosis of CAS.This review mainly introduced the origin and activation of complement molecules inside the plaques,their important roles in the pathogenesis of CAS,and the value of complement molecules as potential predictors in clinical.
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Objective To investigate if the relative ratio between C1q and C3a, C5a had a relationship with the extent of coronary artery disease ( CAD) which had never been evaluated in humans.Methods Fifty-three patients scheduled for elective percutaneous coronary intervention ( PCI ) from February, 2016 to April, 2016 at Fuwai hospital were prospectively enrolled.According to the clinical and angiographic characters patients were divided into two groups:acute coronary syndrome ( ACS) group ( n=24), and control group (n=29, 19 patients with stable angina and 10 patients without CAD confirmed by angiography).In all individuals, fasting venous blood was collected by EDTA tubes after admission and strictly before PCI.The plasma level of C1q was measured by immune turbidimetric analysis, C3a and C5a were measured by ELISA tests.Differences between groups were assessed using t test, Mann-Whitney Utests, chi-squared test or Fisher exact test depending on the type of data respectively.Multivariate logistic regression analyses were conducted to evaluate the adjusted effect of C1q, C3a, C5a, C1q/C3a and C1q/C5a on ACS.Results Compared with control group, ACS group has an elevated circulation level of C3a (4 531.14 μg/L vs.4 179.95 μg/L, t=1.381,P=0.173) and C5a (6.44 μg/L vs.4.42 μg/L, t=0.133, P=0.108) but a decreased level of C1q (176.98 μg/ml vs.200.60 μg/ml, t=-2.022, P=0.048).The relative ratio of C1q/C3a was significantly decreased in ACS patients(4.05 ×10 -2 vs.4.97 × 10 -2 , t=-2.484, P=0.016).According to the multiple logistic regression analysis, lower relative ratio of C1q/C3a level proved to be independently associated with ACS ( OR=0.937, P=0.047, 95% CI:0.879-0.998).Conclusions The decreased relative ratio of C1q/C3a level proved to be independently associated with ACS.C1q/C3a ratio could be used as an important index reflecting the complement system homeostasis status which might have potential clinical value in evaluating the prognosis of patients with CAD.
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Objective: To evaluate the safety and efifcacy of cutting balloon combining main branch single stent cross-over technique for treating the patients with coronary bifurcation lesions. Methods: A total of 113 patients with 121 bifurcation lesions treated in our hospital from 2012-01 to 2014-01 were enrolled. Cutting balloon pre-dilation was applied in both main and side branches followed by drug-eluting stent implantation at main branch. The procedural success rates, side branch blood lfow status and complications were observed. Follow-up studied for MACE occurrence was conducted at 9 months after the operation. Results: Quantitative coronary angiography (QCA) presented that the minimum lumen diameters at pre- and post-operation in main branches were (2.12 ± 1.07) mm and (3.24 ± 0.87) mm, in side branches were (1.44 ± 0.73) mm and (1.82 ± 0.64) mm respectively,P<0.05-0.01, the procedural success rate was 100%. There were 11 (9.1%) lesions with dissection at proximal side branch, 5 (4.1%) lesions with side branch TIMI blood lfow
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<p><b>OBJECTIVE</b>To explore the related factors of optical coherence tomography (OCT) detected in-stent heterogeneous neointimal in coronary stents.</p><p><b>METHODS</b>A total of 143 cases of coronary heart disease patients with OCT detected in-stent neointimal hyperplasia in Fuwai hospital from September 2009 to April 2012 were included in this study and patients data were retrospectively analyzed. Patients were divided into heterogeneous intima group(26 cases) and homogeneous intima group(117 cases)according to neointimal characteristics. Clinical features and OCT characteristics of the 2 groups were compared and binary logistic regression analysis was performed to analyze the risk factors of in-stent heterogonous neointimal hyperplasia.</p><p><b>RESULTS</b>Compared to homogeneous intima group, patients in heterogeneous intima group had significantly higher cholesterol level ((5.31±1.11)mmol/L vs.(4.70±0.94)mmol/L, P=0.005), low-density lipoprotein cholesterol level ((2.57±0.87)mmol/L vs.(2.29±0.46)mmol/L, P=0.021) and triglyceride level (2.12(1.82-2.87)mmol/L vs. 1.90(1.73-2.11)mmol/L, P=0.015). Moreover, the percent of percutaneous coronary intervention (PCI) because of acute coronary syndrome (23.1%(6/26) vs. 6.8%(8/117), P=0.022) and the thin cap neoatheroma (5.8%(28/481)vs. 3.9%(89/2 276), P=0.043) were also significantly higher in heterogeneous intima group than in homogeneous intima group. Binary logistic regression analysis showed that low-density lipoprotein cholesterol (OR=2.74, 95%CI 1.04-7.24, P=0.042), triglyceride (OR=2.88, 95%CI 1.05-7.89, P=0.040), PCI for acute coronary syndrome (OR=12.74, 95%CI 2.69-60.49, P=0.001), and cerebrovascular disease (OR=13.09, 95%CI 2.16-79.53, P=0.005) were risk factors for in-stent heterogenous intima. Time post stent implantation was protective factor for in-stent heterogenous intima (OR=0.63, 95%CI 0.42-0.96, P=0.033).</p><p><b>CONCLUSION</b>OCT detected heterogeneous intima is correlated with level of blood lipid, PCI for acute coronary syndrome and history of cerebrovascular disease, and it may lead to unstable intima.</p>
Subject(s)
Humans , Acute Coronary Syndrome , Coronary Artery Disease , Hyperplasia , Neointima , Percutaneous Coronary Intervention , Retrospective Studies , Risk Factors , Stents , Tomography, Optical Coherence , Tunica IntimaABSTRACT
Different types of noncoding RNAs (ncRNAs) are pervasively expressed in genomes of complex organisms.Current evidence suggests that long noncoding RNAs (lncRNAs) have significant roles at almost every stage of gene expression.It is an important regulatory factor involving in ischemic heart diseases,participating in the development of ischemic heart disease,expecting to predict early myocardial remodeling after myocardial infartion and heart failure,and attracting more and more attention.This review introduces the definition,classification,function and characteristics of lncRNA,and focuses on its diagnostic and predictive value in ischemic heart disease.
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Objective: To analyze the thromboelastography (TEG) outcomes in patients with stable angina pectoris (SAP) combining diabetes mellitus (DM). Methods: A total of 360 SAP patients treated in our hospital by percutaneous coronary intervention (PCI) from 2012-01 to 2013-06 were randomized into 2 groups:SAP+DM group, n=109 and SAP-DM group, n=251. Routine clinical examination and TEG test were performed and compared between 2 groups. Results: Compared with SAP-DM group, SAP+DM group showed the higher ratios of male gender, history of hypertension, hyperlipidemia and higher level of hs-CRP, all P Conclusion: The SAP patients combining DM were at hyper-coagulation status with higher incidence of clopidogrel resistance, who needed intensive post-operative anti-platelet therapy.
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As a new biomarker and a member of transforming growth factor super family,growth differentiation factor-15 (GDF-15) is increased in some pathological situations,and plays a positive role.Increasing evidence from animals and clinical trials has indicated that GDF-15 is a promising biomarker to be used for diagnosis,screening,risk stratification and prognosis evaluation in acute coronary syndrome,heart failure and pulmonary vascular diseases.However,there are still numerous challenges and problems need to be resolved in the future,such as appropriate cut-off value in diagnosis and risk stratification in different cardiovascular diseases,improvement in sensitivity and specificity,and combinational application with other biomarkers.
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As an emergent attack,dyspnea can be caused by a variety of diseases,therefore,it is difficult and important as to the differential diagnosis in clinical practice.In the past,Physicians identified the cause of dyspnea primarily based on the clinical symptoms,signs and laboratory tests.However,dyspnea often misdiagnosed because the similarity and overlapping of clinical manifestations among many different diseases and lack of specificity for those conventional lab tests.Until recently,B-type natriuretic peptide (BNP) has emerged as a highly sensitive and specific index to identify heart failure,and has made it reality that rapid and accurate differential diagnosis of dyspnea in the lab.In the last couple of years,the differential diagnosis of dyspnea has been remarkably improved because of the increasing new test reagents,advanced devices and better assay techniques.The present article will review the laboratory differential diagnosis of dyspnea between cardiovascular and pulmonary diseases.