Abstract 387: Role of STAT3 in Collagen Deposition and Organization in the Normal and Hypertensive Heart
Hypertension causes concentric hypertrophy of the left ventricle that may progress to systolic heart failure by means not defined. We reported that mice with a S727A reduced function mutation in STAT3 have reduced systolic function with angiotensin II (Ang II)-induced hypertension and foci of fibrotic collagen in the myocardium as occurs in hypertensive heart disease. We applied image analysis of relative density (IOD/A) and fractal dimension (D) to quantify foci. Hypertension in WT mice did not affect % area and relative density, but D values decreased (P<0.001) suggesting tighter packing of fibrotic collagen stiffening the myocardium. SA/SA+saline hearts showed significant increases in fibrotic collagen (P=0.025) and density (P<0.001) vs. WT hearts. D values indicate an increase (P=0.002) in chaos of collagen matrix. In SA/SA mice Ang II caused remodeling of myocardial collagen with loss of myocytes within fibrotic foci. Hypertension in SA/SA hearts induced further increase (P<0.001) in collagen, while the relative density was significantly less (P=0.015) than the SA/SA+saline group but greater than WT+saline and WT+Ang II groups. The decrease in collagen density was associated with a large (P<0.001) increase in D values, indicating collagen in fibrotic foci was highly disorganized and more space filling. Loss of myocytes and their replacement by chaotic and randomly organized collagen may further weaken the myocardium leading to systolic heart failure. Our results show that STAT3 is essential in normal regulation and organization of the collagen matrix in the heart. Suppression of STAT3 results in fibrotic lesions in the myocardium that are exacerbated by hypertension.
- © 2013 by American Heart Association, Inc.