Microtubule-associated protein 1S (MAP1S): a cardioprotective factor against post-myocardial infarction remodeling via apoptosis inhibition

Abstract

Adverse cardiac remodeling following myocardial infarction (MI) are driven by processes including autophagy and apoptosis. While microtubule-associated protein 1S (MAP1S) is known to regulate autophagy, its role in the cardiac pathological conditions remains unclear. This study aimed to elucidate the role of MAP1S and its underlying mechanisms in pathological cardiac remodeling. Following MI, MAP1S knockout mice exhibited increased mortality, impaired cardiac function, and elevated apoptosis. Similarly, MAP1S silencing in cultured cardiomyocytes augmented apoptosis under oxidative stress. Mechanistic investigation revealed potential link to the Hippo pathway. MAP1S knockdown in cardiomyocytes increased Mammalian Ste-20 like 1/2 (MST1/2) activation and reduced Yes-associated protein (YAP) activity, potentially explaining apoptosis regulation. Conversely, MAP1S overexpression reduced apoptosis and positively modulated autophagy. Importantly, in vivo modRNA-mediated MAP1S overexpression protected against apoptosis and adverse remodeling. This study reveals that MAP1S protects the heart from excessive apoptosis and adverse remodeling following MI, likely by modulating the Hippo signaling pathway.