Zyxin protects from hypertension-induced cardiac dysfunction.

Area of Science:

• Cardiovascular Biology
• Mechanobiology
• Molecular Cardiology

Background:

• Arterial hypertension induces left ventricular hypertrophy and dilated cardiomyopathy.
• Cardiac dysfunction arises from cardiomyocyte loss and fibrosis, following initial hypertrophy.
• Zyxin, a mechanotransducer in vascular cells, may support cardiomyocyte survival.

Purpose of the Study:

• To investigate the role of zyxin in cardiac function during experimental hypertension.
• To analyze the impact of zyxin deficiency on cardiac remodeling and dysfunction under hypertensive conditions.

Main Methods:

• Experimental hypertension induced using deoxycorticosterone acetate (DOCA)-salt or angiotensin II in zyxin knockout (KO) mice.
• Cardiac function assessed via telemetry, echocardiography, and isolated working heart measurements.
• Analysis of cardiomyocyte apoptosis, cardiac fibrosis, focal adhesion kinase, and integrin expression.

Main Results:

• Zyxin KO mice showed attenuated blood pressure rise but developed systolic dysfunction and decreased systolic elastance under hypertension.
• Hypertensive zyxin KO hearts exhibited increased apoptosis, interstitial and perivascular fibrosis, and upregulated active focal adhesion kinase, integrin α5, and β1.
• Fibrosis was more severe with angiotensin II compared to DOCA-salt treatment.

Conclusions:

• Zyxin deficiency unmasks a cardiac phenotype under hypertension, leading to dysfunction.
• Enhanced cardiomyocyte apoptosis and fibrosis in zyxin KO mice contribute to cardiac dysfunction.
• Zyxin is crucial for maintaining cardiac function during hypertension, potentially by limiting fibrosis and apoptosis.