郝云玲
深圳市孙逸仙心血管医院 老年病科
Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.
Experimental cell research 2021
This study evaluated the benefit of dual therapy in reducing ischemic events in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). We searched PubMed, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing dual and triple therapies (oral anticoagulation plus aspirin and P2Y12 inhibitor) for AF patients with ACS or those undergoing PCI. The composite primary outcome included all-cause death, myocardial infarction (MI), stent thrombosis (ST), or stroke. Relative risk (RR) and the corresponding 95% confidence interval (CI) was used as the measure of effect size. Four RCTs with 10,969 patients were included. Dual therapy had a higher event rate of primary outcome than triple therapy (RR, 1.15; 95%CI, 1.03-1.28; P<0.0001). Dual therapy was associated with significantly higher MI risk, insignificantly higher ST risk, and significantly lower major bleeding risk than triple therapy (RR1.23, 95%CI 1.01-1.49, P = 0.036; RR 1.43, 95 %CI 0.98-2.09, P = 0.064; and RR0.58, 95%CI 0.45-0.76, P<0.0001, respectively). Dual antithrombotic therapy was associated with higher ischemic risk but lower major bleeding risk than triple therapy. The data suggest that antithrombotic regimens should be based on tradeoffs between ischemia and bleeding risk.
Aging 2020
