Hyperhomocysteinemia Promotes Cardiac Hypertrophy in Hypertension

Area of Science:

• Cardiovascular Research
• Metabolic Disease Mechanisms
• Molecular Cardiology

Background:

• Hyperhomocysteinemia (HHcy) is linked to cardiovascular diseases, but its specific role in pathological cardiac hypertrophy remains unclear.
• Hypertensive cardiac hypertrophy is a common condition where the underlying mechanisms involving HHcy require elucidation.

Purpose of the Study:

• To investigate the effects of HHcy on hypertensive cardiac hypertrophy.
• To explore the underlying molecular mechanisms, specifically the Calcineurin-NFAT pathway, involved in HHcy-induced cardiac hypertrophy.

Main Methods:

• Retrospective analysis of HHcy and cardiac hypertrophy in a hypertensive cohort.
• Induction of HHcy in mice using a methionine diet, followed by angiotensin II infusion to model hypertensive cardiac hypertrophy.
• Assessment of cardiac phenotypes, inflammation, fibrosis, and molecular signaling (Calcineurin-NFAT) in response to HHcy and folic acid treatment.
• In vitro studies using neonatal rat cardiomyocytes treated with homocysteine and cyclosporin A.

Main Results:

• HHcy was more prevalent in hypertensive patients with cardiac hypertrophy and significantly associated with its presence.
• HHcy exacerbated angiotensin II-induced cardiac hypertrophy, inflammation, and fibrosis in mice.
• Folic acid supplementation corrected HHcy and attenuated angiotensin II-stimulated cardiac changes.
• Homocysteine enhanced angiotensin II-induced Calcineurin-NFAT signaling, which was blocked by folic acid and cyclosporin A in cardiomyocytes.

Conclusions:

• HHcy promotes cardiac hypertrophy in the context of hypertension.
• The Calcineurin-NFAT signaling pathway is implicated in the pro-hypertrophic effects of homocysteine.
• Targeting HHcy and the Calcineurin-NFAT pathway may offer therapeutic strategies for hypertensive cardiac hypertrophy.