TGF-β1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II

Abstract

Angiotensin II (Ang II), a potent hypertrophic stimulus, causes significant increases in TGFb1 gene expression.However, it is not known whether there is a causal relationship between increased levels of TGF-β1 and cardiac hypertrophy.Echocardiographic analysis revealed that TGF-β1-deficient mice subjected to chronic subpressor doses of Ang II had no significant change in left ventricular (LV) mass and percent fractional shortening during Ang II treatment.In contrast, Ang II-treated wildtype mice showed a >20% increase in LV mass and impaired cardiac function.Cardiomyocyte crosssectional area was also markedly increased in Ang II-treated wild-type mice but unchanged in Ang II-treated TGF-β1-deficient mice.No significant levels of fibrosis, mitotic growth, or cytokine infiltration were detected in Ang II-treated mice.Atrial natriuretic factor expression was ∼6-fold elevated in Ang II-treated wild-type, but not TGF-β1-deficient mice.However, the αto β-myosin heavy chain switch did not occur in Ang II-treated mice, indicating that isoform switching is not obligatorily coupled with hypertrophy or TGF-β1.The Ang II effect on hypertrophy was shown not to result from stimulation of the endogenous renin-angiotensis system.These results indicate that TGF-β1 is an important mediator of the hypertrophic growth response of the heart to Ang II.