Enhanced Cardiomyocyte NLRP3 Inflammasome‐Mediated Pyroptosis Promotes d ‐Galactose–Induced Cardiac Aging

作者：Wenbin Liu, Sui-Sui Wang, Xu Zhang, Zezhi Ke, Xiu‐yun Wen, Jie Zhao, Xiaodong Zhuang, Lizhen Liao · 发表于：Journal of the American Heart Association · 年份：2024 · DOI：10.1161/jaha.123.032904 · 被引用次数：35 · 研究领域：Inflammasome and immune disorders、Antioxidants, Aging, Portulaca oleracea、Telomeres, Telomerase, and Senescence

Background Cardiac aging represents an independent risk factor for aging‐associated cardiovascular diseases. Although evidence suggests an association between NOD‐, LRR‐, and pyrin domain–containing protein 3 (NLRP3) inflammasome formation and numerous cardiovascular diseases, its role in cardiac aging remains largely unclear. Methods and Results The longevity of mice with wild‐type and NLRP3 knockout (NLRP3 −/− ) genotypes was assessed, with or without d ‐galactose treatment. Cardiac function was evaluated using echocardiography, and cardiac histopathology was examined through hematoxylin and eosin and Masson's trichrome staining. Senescence‐associated β‐galactosidase (SA‐β‐gal) staining was employed to detect cardiac aging. Western blotting was used to assess aging‐related proteins (p53, p21) and pyroptosis‐related proteins. Additionally, dihydroethidium staining, lactate dehydrogenase release, and interleukin‐1β ELISA assays were performed, along with measurements of total superoxide dismutase and malondialdehyde levels. In vitro, H9c2 cells were exposed to d ‐galactose for 24 hours in the absence or presence of N ‐acetyl‐ l ‐cysteine (reactive oxygen species inhibitor), BAY‐117082 (nuclear factor κ‐light‐chain enhancer of activated B cells inhibitor), MCC950 (NLRP3 inhibitor), and VX‐765 (Caspase‐1 inhibitor). Immunofluorescence staining was employed to detect p53, gasdermin D, and apoptosis‐associated speck‐like protein proteins. Intracellular reactive oxygen species lev...