Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the Beclin-1 pathway.

The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of acetaldehyde and endogenous lipid aldehydes. Approximately 40% of East Asians, accounting for 8% of the human population, carry the E504K mutation in ALDH2 that leads to accumulation of toxic reactive aldehydes and increases the risk for cardiovascular disease, cancer, and Alzheimer disease, among others. However, the role of ALDH2 in acute kidney injury (AKI) remains poorly defined and is therefore the subject of the present study using various cellular and organismal sources. In murine models, in which AKI was induced by either the contrast agent iohexol or renal ischemia/reperfusion, KO, activation/overexpression of ALDH2 were associated with increased and decreased renal injury, respectively. In murine renal tubular epithelial cells (RTECs), ALDH2 upregulated Beclin-1 expression, promoted autophagy activation, and eliminated ROS. In vivo and in vitro, both 3-MA and Beclin-1 siRNAs inhibited autophagy and abolished ALDH2-mediated renoprotection. In mice with iohexol-induced AKI, ALDH2 knockdown in RTECs using AAV-shRNA impaired autophagy activation and aggravated renal injury. In human renal proximal tubular epithelial HK-2 cells exposed to iohexol, ALDH2 activation potentiated autophagy and attenuated apoptosis. In mice with AKI induced by renal ischemia/reperfusion, ALDH2 overexpression or pretreatment regulated autophagy mitigating apoptosis of RTECs and renal injury. In summary, our data collectively substantiate a critical role of ALDH2 in AKI via autophagy activation involving the Beclin-1 pathway.

Omission of aspirin in patients taking oral anticoagulation after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: There is no consensus on optimal antiplatelet and anticoagulation therapy after coronary stenting. METHODS: We identified randomized controlled trials (RCTs) published in PubMed, Cochrane Library, and Embase using the following keywords: 'antiplatelet', 'dual therapy', 'triple therapy', 'antithrombosis', 'indication for anticoagulation', 'percutaneous coronary intervention', and 'RCTs'. Primary safety end points were relative bleeding events, and secondary efficacy end points were major adverse cardiovascular events including stent thrombosis, death, myocardial infarction, and stroke. RESULTS: We identified three RCTs including 5387 patients, of whom 2719 (50.5%) received dual therapy (DT) and 2668 (49.5%) received triple therapy. Relative to triple therapy, DT was associated with lower Thrombolysis in Myocardial Infarction major bleeding [risk ratio (RR): 0.58; 95% confidence interval (CI): 0.42-0.82], Thrombolysis in Myocardial Infarction minor bleeding (RR: 0.46; 95% CI: 0.34-0.62), and clinical bleeding events (RR: 0.61; 95% CI: 0.47-0.81). There was no significant difference for the secondary efficacy end point. In subgroup analyses, results were similar by sex, bleeding risk, and stent type; however, DT appeared suitable for patients aged less than 75 years but not more than or equal to 75 years, implying that there may be no ideal therapy for patients older than 75 years to balance the risk of ischemia and bleeding at the same time. CONCLUSION: Among patients with an indication for oral anticoagulation after percutaneous coronary intervention, DT appears to be the optimal strategy.