Transforming growth factor (TGF)-β1 is a known factor in angiotensin II (Ang II)-mediated cardiac fibrosis after myocardial infarction (MI). Hypoxia inducible factor-1 (Hif-1α) was recently demonstrated to involve in the tissue fibrosis and influenced by Ang II. However, whether Hif-1α contributed to the Ang II-mediated cardiac fibrosis after MI, and whether interaction or synergetic roles between Hif-1α and TGF-β pathways existed in the process was unclear. In vitro, cardiac cells were incubated under hypoxia or Ang II to mimic ischaemia. In vivo, valsartan was intravenously injected into Sprague–Dawley rats with MI daily for 1 week; saline and hydralazine (another anti-hypertensive agent like valsartan) was used as control. The fibrosis-related proteins were detected by Western blotting. Cardiac structure and function were assessed with multimodality methods. We demonstrated in vitro that hypoxia would induce the up-regulation of Ang II, TGF-β/Smad and Hif-1α, which further induced collagen accumulation. By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up-regulation of TGF-β/Smad and Hif-1α was through the Ang II-mediated pathway. By administering TGF-β or dimethyloxalylglycine, we determined that both TGF-β/Smad and Hif-1α contributed to Ang II-mediated collagen accumulation and a synergetic effect between them was observed. Consistent with in vitro results, valsartan significantly attenuated the expression of TGF-β/Smad, Hif-1α and fibrosis-related protein in rats after MI. Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine. Our study may provide novel insights into the mechanisms of Ang II-induced cardiac fibrosis as well as into the cardiac protection of valsartan.

Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

Purpose: Current evidence supports a robust association between obstructive sleep apnea syndrome (OSAS) and the risk of coronary artery disease (CAD). YKL-40, a 40 kDa heparin- and chitin-binding glycoprotein, is found to be associated with the presence of CAD. This study aims to examine the association of serum levels of YKL-40 with the presence and severity of CAD in patients with OSAS. Methods: A total of 246 patients with OSAS who underwent coronary angiography for the evaluation of CAD (134 patients with CAD and 112 patients without CAD) were enrolled in this study. The severity of CAD was assessed using the coronary atherosclerosis index (CAI). Serum levels of YKL-40 were determined using enzyme-linked immunosorbent assay. Results: Serum YKL-40 levels were significantly higher in OSAS patients with CAD compared with those without CAD. Multivariable logistic regression analysis revealed that serum YKL-40 levels were an independent determinant of the presence of CAD in patients with OSAS. In addition, Spearman correlation analysis showed that serum YKL-40 levels were positively correlated with CAI in OSAS patients with CAD. Patients with statin treatment showed significantly lower levels of serum YKL-40 compared with those without. Conclusions: Elevated levels of serum YKL-40 are associated with the presence and severity of CAD in patients with OSAS.

Angiotensinogen, one of the most important proteins in the renin-angiotensin system, plays a key role in the progress of coronary heart disease and myocardial infarction (MI). Many studies have investigated the association between angiotensinogen gene M235T polymorphism and MI risk, but the results were inconsistent. We performed a meta-analysis of 22 studies on M235T polymorphism and MI risk published before November 2012. This meta-analysis included a total of 4,606 MI cases and 4,918 controls. Overall, the per-allele odds ratio (OR) of the 235T variant for total MI risk was 1.04 (95 % CI 0.92-1.17). When a recessive model was evaluated, the OR was 1.06 (95 % CI 0.96-1.17) and under a dominant model, the OR was 0.96 (95 % CI 0.82-1.11). Under pairwise comparisons, non-significant associations were found between M235T polymorphism and MI risk (MT vs. MM, OR, 0.96, 95 % CI 0.87-1.06; TT vs. MM, OR, 1.03, 95 % CI 0.83-1.28). Subgroup analyses in the different ethnic groups and different control sources were performed and no significant association was found also. Based on the available evidence, no association between M235T polymorphism and MI risk was observed, even in the sub-analysis concerning different races and control sources. The direction of further research should focus not only on the simple relationship of M235T polymorphism and MI risk, but also on gene-gene and gene-environment interaction.

No abstract