Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Family Health University College and Hospital, Opposite Kofi Annan International Peace Keeping Training Center, Teshie- Accra, Ghana.
PeerJ. 2024 Nov 13;12:e18499. doi: 10.7717/peerj.18499. eCollection 2024.
Myoferlin (MYOF) is a muscle-derived secretory protein. Recent studies have found that MYOF protects against cell damage. However, the role of MYOF in cardiac hypertrophy remains unclear. Increasing evidence suggests that NLRP3 (NOD-like receptor protein 3) and the pyroptosis cascade play critical roles in the development of cardiac hypertrophy and inflammation. To investigate the role of MYOF in cardiac hypertrophy, we conducted a transverse aortic constriction (TAC) experiment in a mouse model. We found that MYOF can improve cardiac hypertrophy and cardiac function. Furthermore, our study confirmed a connection between cardiac hypertrophy and myocardial pyroptosis. Cardiac hypertrophy significantly increased the proportion of apoptotic cells and upregulated apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and gasdermin D (GSDMD). This suggests that pharmacological or genetic inhibition of NLRP3 can effectively reduce cardiac hypertrophy. An abnormal increase in NLRP3 can reverse the cardioprotective effects of MYOF. Our findings indicate that MYOF is a potential therapeutic agent for cardiac hypertrophy.
肌联蛋白（MYOF）是一种肌肉来源的分泌蛋白。最近的研究发现，MYOF 可防止细胞损伤。然而，MYOF 在心肌肥厚中的作用尚不清楚。越来越多的证据表明，NLRP3（NOD 样受体蛋白 3）和焦亡级联在心肌肥厚和炎症的发展中起关键作用。为了研究 MYOF 在心肌肥厚中的作用，我们在小鼠模型中进行了横主动脉缩窄（TAC）实验。我们发现 MYOF 可以改善心肌肥厚和心功能。此外，我们的研究证实了心肌肥厚与心肌焦亡之间的联系。心肌肥厚显著增加了凋亡细胞的比例，并上调了凋亡相关斑点样蛋白（ASC）、半胱氨酸天冬氨酸蛋白酶 1（caspase-1）和 Gasdermin D（GSDMD）。这表明，NLRP3 的药理学或遗传学抑制可以有效减少心肌肥厚。NLRP3 的异常增加可以逆转 MYOF 的心脏保护作用。我们的研究结果表明，MYOF 是一种治疗心肌肥厚的潜在药物。
