RBP1 attenuates pathological cardiac hypertrophy via Wnt3a/β-catenin signaling

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Retinoid Signaling

Background:

• Pathological cardiac hypertrophy drives heart failure, necessitating targeted therapies.
• Retinoid homeostasis, regulated by retinol-binding protein 1 (RBP1), is implicated in cardiac hypertrophy.
• The precise role and mechanisms of RBP1 in cardiac hypertrophy require elucidation.

Purpose of the Study:

• To investigate the role of RBP1 in cardiac hypertrophy.
• To elucidate the underlying mechanisms of RBP1's action in cardiac hypertrophy.
• To explore RBP1 as a potential therapeutic target for heart failure.

Main Methods:

• Quantified cardiac retinol and all-trans retinoic acid (atRA) using LC-MS.
• Utilized a mouse model of pressure overload-induced cardiac hypertrophy (transverse aortic constriction).
• Employed cardiac-specific RBP1 overexpression via AAV9 vectors and in vitro models with phenylephrine-treated cardiomyocytes.

Main Results:

• Impaired retinol metabolism and cardiac hypertrophy were observed in mice subjected to pressure overload.
• RBP1 overexpression ameliorated cardiac hypertrophy and fibrosis, restoring retinol and atRA levels.
• RBP1 attenuated cardiomyocyte hypertrophy by suppressing Wnt3a/β-catenin signaling in an atRA-dependent manner.

Conclusions:

• RBP1 is upregulated in hypertrophic myocardium and exerts a protective effect against cardiac hypertrophy.
• RBP1, through the RBP1/atRA/Wnt3a/β-catenin pathway, represents a potential therapeutic target for cardiac hypertrophy and heart failure.