Yian Yao

Inhibitory effect of atorvastatin on AGE-induced HCAEC apoptosis by upregulating HSF-1 protein.

This study evaluates effect and mechanism of atorvastatin on human coronary artery endothelial cells (HCAEC) apoptosis. Results have shown that HCAEC apoptosis had increased with increasing concentration of AGEs. Atorvastatin may decrease HCAEC apoptosis, but the effect can be attenuated by PI3K inhibitor. Secretion of PI3K and P-Akt in HCAEC increased with increasing concentration of AGEs. Secretion of PI3K in HCAEC may be decreased by atorvastatin. The effect may be attenuated by PI3K inhibitor. HSF-1, HSP-70 mRNA expression level decreased with increasing concentration of AGEs. Atorvastatin may attenuate AGEs-induced HSF-1, HSP-70 mRNA expression in HCAEC, but the effect can be attenuated by PI3K inhibitor. It can be concluded that AGE can dose-dependently promote HCAEC apoptosis by the PI3K/AKT pathway. Atorvastatin may attenuate the effect possibly by upregulating HSF-1.

Fibroblast growth factor receptor 4 polymorphisms and susceptibility to coronary artery disease.

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play crucial roles in vascular smooth muscle cell proliferation and atherosclerosis and, therefore, may potentially affect the development of coronary artery disease (CAD). FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to CAD in the Chinese population. Two polymorphisms, rs351855 (Gly388Arg) and rs641101, were detected by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing in 687 CAD cases and 732 age-matched controls. Data were analyzed using the chi-square test. Results showed that frequencies of GA genotype, AA genotype, and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls (odds ratio (OR)=0.78, 95% confidence intervals (CIs): 0.62-0.98, p=0.034; OR=0.58, 95% CI: 0.42-0.80, p=0.001; and OR=0.77, 95% CI: 0.66-0.90, p=0.001, respectively). The rs641101 polymorphism did not show any correlation with CAD. Haplotype analysis revealed that rs351855 and rs641101 AG haplotype also had lower frequency in CAD patients (OR=0.79, 95% CI: 0.67-0.92, p=0.002). Our data suggested that the FGFR4 rs351855 (Gly388Arg) polymorphism and AG haplotype (rs351855 and rs641101) could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases.

Coronary Artery Aneurysm Differs From Coronary Artery Ectasia Angiographic Characteristics and Cardiovascular Risk Factor Analysis in Patients Referred for Coronary Angiography

The differences in angiographic characteristics and cardiovascular (CV) risk factors between coronary artery aneurysm (CAA) and coronary artery ectasia (CAE) have not been compared systematically. Of 10 876 patients undergoing coronary angiography, patients with CAA (n = 85) and CAE (n = 51) were screened. The prevalence of CAA was greater than that of CAE (P < .05). The right coronary artery was the most involved (70.6%) in CAE compared with left circumflex (52.9%) and left anterior descending (41.2%). Coronary artery aneurysm coexisted with coronary artery disease (CAD) more frequently than CAE (P = .002), and the modified Gensini score of CAA was also higher than that of CAE (P < .001). The average maximum diameter was smaller, and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count was lower in CAA than CAE in all 3 coronary arteries (P < .001). Multivariate analysis showed that hyperlipidemia (P = .02), smoking (P = .04), and family history of CAD (P = .02) were the independent variables most strongly associated with CAA, but not CAE. This study suggests that there are significant differences in coronary angiographic characteristics and CV risk factors between CAA and CAE.

Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome

Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the VerifyNow P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C19*2 and CYP2C19*17 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P<0.001). Patients with CYP2C19*2 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918–15.399, P=0.01). The coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C19*3 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C19*2, CYP2C19*17 coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients.

Combination of P2Y12 reaction unit and percentage of platelet inhibition assessed by VerifyNow P2Y12 assay is a useful predictor of long-term clinical outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention

INTRODUCTION High on-treatment platelet reactivity is a well-known risk factor for adverse events in patients undergoing percutaneous coronary intervention (PCI). This study was to investigate the value of a novel platelet reactivity-based system, named the COP-INH (COmbination of P2Y12 reaction unit [PRU] and percentage of platelet inhibition [%INH]), assessed by VerifyNow P2Y12 assay, for predicting the long-term ischaemic events in patients with acute coronary syndrome (ACS) undergoing PCI. MATERIALS AND METHODS The COP-INH was calculated on the basis of data obtained at 30days after PCI: patients with both an elevated PRU (≥230) and decreased %INH (<40%) were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. The primary endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization at 1year follow-up. The relationship between the COP-INH score and primary endpoint was analyzed. RESULTS 207 patients were enrolled. Baseline characteristics were similar between patients with COP-INH=2 and patients with COP-INH=1 or 0, except for diabetes mellitus (43.8% vs. 21.7%, p=0.015) and previous coronary artery bypass grafting (CABG) (21.9% vs. 6.86%, p=0.007). During the observation period, the incidence of major adverse cardiovascular events (MACE) in patients with COP-INH=2 was significantly higher than patients with COP-INH=1 or 0 (18.8% vs. 4.6%, p=0.007). Multivariate analysis of clinical characteristics and platelet reactivity selected by univariate analysis showed that the COP-INH=2 was an independent predictor of MACE in patients with ACS undergoing PCI (OR 2.745; 95% CI 1.369-9.851; p=0.024), whereas neither PRU≥230 nor %INH<40% was. CONCLUSION The COP-INH is considered to be a useful predictor of long-term ischaemic events of patients with ACS undergoing PCI.

Mechanical stretch changes coronary artery fibroblasts function by upregulating HSF1 protein expression.

The study is designed to investigate effect of mechanical stretch on the function of fibroblast cells. Human coronary artery fibroblasts were cultured. They were divided into two groups: stretch group (stretch for 24h) and no-stretch group (did not stretch). ELISA analysis was used for detection of collagen secretion. CCK-8 method was used for detection of cells proliferation. RT-PCR method was used for detection of MMP, TIMP, IL-6, alpha-SMA, HSF1 and HSP70 mRNA expression. Western-blotting method was used for detection of HSF1 protein expression. Results showed that cells proliferation in stretch group was stronger than that in no-stretch group. Hydroxyproline secretion in stretch group was more than that in no-stretch group. MMP-9/TIMP, alpha-SMA, IL-6, HSF1 and HSP70 in stretch group was higher than those in no-stretch group. Western-blotting analysis showed that HSF1 protein expression was upregulated in stretch group. It can be concluded that mechanical stretch changed human coronary artery fibroblasts cells proliferation, collagen formation, the secretion of inflammatory factor possibly by upregulating HSF1 protein expression.

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus

Background/Aims: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. Methods: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. Results: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. Conclusions: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.

Fusiform Appearance of Myocardial Bridging Detected by OCT

Myocardial bridging (MB) is characterized by epicardial coronary artery tunneling through the myocardium, with angiographic “milking” and an intravascular ultrasound (IVUS) “half-moon” echolucent [(1)][1]. Optical coherence tomography (OCT), a light-based technique, can provide unprecedented