Exogenous cathepsin V protein protects human cardiomyocytes HCM from angiotensin Ⅱ-Induced hypertrophy

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Cellular Signaling

Background:

• Cardiac hypertrophy, induced by Angiotensin II, is a major precursor to heart failure and mortality.
• Endogenous Cathepsin V (CTSV) exhibits cardioprotective properties, but the effects of exogenous CTSV remain largely unexplored.
• Understanding CTSV's role is crucial for developing novel therapeutic strategies against cardiac hypertrophy.

Purpose of the Study:

• To investigate the protective effects of exogenous Cathepsin V (CTSV) against Angiotensin II-induced cardiac hypertrophy in human cardiomyocytes.
• To elucidate the underlying molecular mechanisms, focusing on PI3K/Akt/mTOR and MAPK signaling pathways.
• To provide evidence for the potential therapeutic application of CTSV in cardiac hypertrophy.

Main Methods:

• Utilized human cardiomyocytes (HCM) as an in vitro model for Angiotensin II-induced cardiac hypertrophy.
• Assessed cell surface area and expression of hypertrophy markers (ANP, BNP, β-MHC) to quantify hypertrophy.
• Analyzed the phosphorylation levels and activities of key proteins within the PI3K/Akt/mTOR and MAPK signaling pathways.

Main Results:

• Exogenous CTSV pre-treatment significantly inhibited Angiotensin II-induced hypertrophy in HCM cells.
• CTSV treatment effectively reduced the elevated mRNA expression of hypertrophy markers ANP, BNP, and β-MHC.
• CTSV's cardioprotective effects were associated with the repression of PI3K/Akt/mTOR and MAPK pathway protein phosphorylation.

Conclusions:

• Exogenous CTSV demonstrates significant cardioprotective effects against Angiotensin II-induced cardiac hypertrophy in human cardiomyocytes.
• The mechanism involves the inhibition of the PI3K/Akt/mTOR signaling pathway.
• CTSV presents a promising therapeutic candidate for the treatment of cardiac hypertrophy.