MBNL1 Modulates Nek7 to Facilitate Pathological Cardiac Hypertrophy via NLRP3

作者：Chao Li, Xiaona Wang, Ruonan Yang, Yao Liu, Linzhu Wang, Mingxiu Zhang, Juan Dong, Liangliang Li, Tong Yu, Lifang Lv, Tianyu Li, Ying Zhang, Bai‐Yan Li, Haihai Liang, Hongli Shan, Xuelian Li · 发表于：Hypertension · 年份：2025 · DOI：10.1161/hypertensionaha.125.24641 · 被引用次数：3 · 研究领域：Cardiomyopathy and Myosin Studies、Congenital heart defects research、Ubiquitin and proteasome pathways

BACKGROUND: Hypertension-induced cardiac hypertrophy constitutes the principal cause of heart failure, malignant arrhythmias, and sudden cardiac death. Nek7 (NIMA-Related Kinase 7), a member of the serine/threonine kinase family, is a multifunctional protein kinase that plays a crucial role in regulating the cell cycle, mitosis, and inflammation, but its role in cardiac hypertrophy remains unclear. METHODS: We subjected AAV9-cTnT-si-Nek7 mice to pressure overload by means of transverse aortic constriction and evaluated cardiac function, cardiac hypertrophy, and inflammasome activation. In neonatal mouse cardiomyocytes treated with Ang (angiotensin) II, the effects of si-Nek7 (small interfering RNA targeting Nek7) or NLRP3 (NLR Family, Pyrin Domain-Containing 3 Protein) inhibition on cardiomyocyte hypertrophy were examined. The effect of Nek7 in regulating cardiac hypertrophy was examined by administering si-MBNL1 (muscleblind-like splicing regulator 1) through tail vein knockdown in transverse aortic constriction treated mice. RESULTS: Nek7 expression was significantly upregulated in both transverse aortic constriction induced cardiac hypertrophy models in vivo and Ang II-stimulated neonatal mouse cardiomyocytes in vitro. Knockdown of Nek7 attenuated Ang II-induced cardiomyocyte hypertrophy and inhibited the activation of the NLRP3 inflammasome. Knockdown of Nek7 with AAV9-si-Nek7 significantly improved cardiac function and reduced hypertrophy in transverse aortic constrictio...