Cardiovascular diseases (CVDs) have been the top-ranked cause of human death in the world for years, according to the World Health Organization. Accumulating evidence from epidemiological data supports the view that the risk of CVDs is higher in northern China than in southern area. There is no doubt that living environment has become a crucial factor contributing to the occurrence and progression of CVDs in northern region. However, there have not been any clinical guidelines for the prevention strategy of environment-related CVDs, especially for cold exposure. Thus, there is an urgent need for better understanding of the clinical characteristics and underlying mechanisms of cold-induced CVDs in order to formulate and implement proper and effective measures for minimizing the risk of CVDs for people residing in low-temperature area. Cold exposure, air pollution, lack of sunlight and irrational diet are believed to be crucial factors responsible for environment-related CVDs, and preventive measures might be carried out accordingly to decrease the high risk of CVDs in northern China.

  Background and Objective  Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance. The Wnt signaling pathway is closely implicated in organ fibrosis, and Notum, a highly conserved secreted inhibitor, modulates Wnt signaling. The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.  Methods  A mouse model of cardiac remodeling was established through left coronary artery ligation surgery, with the addition of Notum injection following myocardial infarction surgery. The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function, including survival rate, echocardiographic assessment, and cardiac contraction analyses. Inflammatory cell necrosis and infiltration were confirmed through H & E and Masson staining. The expression of fibrosis-related genes and β-catenin pathway markers was detected using Western blot quantificational RT-PCR (qRT-PCR). Additionally, EdU, wound healing, and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1 (TGF-β1) induced myofibroblast transformation.  Results  The administration of Notum treatment resulted in enhanced survival rates, improved cardiac function, and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation. Furthermore, Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts. Additionally, it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway. Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.  Conclusion  Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis. Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.

  Objective  There exist conflicting data on the efficacy and safety of ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome (ACS). We performed a meta-analysis to evaluate whether ticagrelor or clopidogrel produces better outcomes for East Asian patients with ACS.  Methods  We searched for randomized controlled trials reporting associations between ticagrelor and clopidogrel in East Asian patients with acute coronary syndrome in PubMed, EMBASE, web of science and Cochrane central register of controlled trials.  Results  Ten studies involving 3 715 participants were qualified for our analysis. The major adverse cardiovascular events (MACE) were significantly decreased in patients with ticagrelor treatment compared to those with clopidogrel (risk ratio [RR]: 0.61; 95% confidence interval [CI]: 0.38-0.98; P = 0.042). There was no significant difference in all-cause death (RR: 0.89; 95% CI: 0.61-1.29; P = 0.540), cardiovascular death (RR: 0.86; 95% CI: 0.58-1.27; P = 0.451), myocardial infarction (RR: 0.91; 95% CI: 0.65-1.27; P = 0.575) and stroke (RR: 0.77; 95% CI: 0.44-1.36; P = 0.372) between ticagrelor and clopidogrel. Ticagrelor was associated with a significantly higher risk of bleeding compared to clopidogrel (RR: 1.71; 95% CI: 1.37-2.13; P = 0.000).  Conclusion  The present meta-analysis demonstrates that ticagrelor reduced the incidence of MACE in ACS patients from East Asia compared with clopidogrel. However, it increased the risk of bleeding.

Objective: Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results: Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1℃), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1℃). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion: TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.