Fortilin inhibits p53, halts cardiomyocyte apoptosis, and protects the heart against heart failure.

ABSTRACT: Heart failure (HF) has reached epidemic proportions in developed countries, affecting over 20 million people worldwide. Despite modern medical and device therapies, 60-70% of HF patients still die within 5 years of diagnosis as it relentlessly progresses through pervasive apoptotic loss of cardiomyocytes. Although fortilin, a 172-amino-acid anti-p53 molecule, is one of the most expressed proteins in the heart, its precise role there has remained unknown. Also unclear is how cardiomyocytes are protected against apoptosis. Here, we report that failing human hearts express less fortilin than do non-failing hearts. We also found that mice lacking fortilin in the heart (fortilin^KO-heart) die by 9 weeks of age due to extensive cardiomyocyte apoptosis and severe HF, which suggests that

SUBMITTER: Chunhacha P 

PROVIDER: S-EPMC8542040 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature