The Association Between Myocardial Fibrosis and Depressed Capillary Density in Rat Model of Left Ventricular Hypertrophy

Abstract

Myocardial fibrogenesis is initiated once the coordination between oxygen supply and demand is disrupted in pressure overload-induced cardiac hypertrophy. Clinical observations showed that myocardial fibrosis did not evenly occur in the hypertrophic myocardium. The present study was undertaken to specifically address differential vulnerabilities to fibrogenesis of different regions in the myocardium subjected to pressure overload-induced hypertrophy. SD rats were divided into two groups, sham-operated control and ascending artery constriction-induced cardiac hypotrophy. Thirty-four weeks after surgery, rats were sacrificed and hearts were harvested. Myocardial tissues were processed and sequentially sectioned for detection of collagen deposition, myocyte hypertrophy and vascular density analysis. Redundant collagen stained with Sirius red and anti-collagen I antibody was found in the extracellular matrix, but high volume of collagen fraction was largely localized more in posterior and lateral walls than in anterior wall and interventricular septum, which is in accordance with the accumulation of fibroblasts. In association with the differential regional collagen accumulation, the cardiomyocytes were more hypertrophic in the posterior and lateral wall than the other left ventricle. However, the capillary density in the lateral and posterior walls was significantly decreased. The results indicated that the posterior and lateral walls were more vulnerable to fibrogenesis post-pressure overload-induced cardiac hypertrophy, which was associated with the depressed angiogenesis in these two regions.

Angiogenic Endothelial Cell Signaling in Cardiac Hypertrophy and Heart Failure

“…This process is termed endothelial-to-mesenchymal transition (EndMT) and has been shown to play a role in the development of kidney (285), lung (286), and cardiac fibrosis (271), among others. In rat hearts with aortic constriction-induced cardiac hypertrophy, local differences in cardiomyocyte hypertrophy and collagen deposition were observed which correlated with local reduction in capillary density (287). Hypoxia was shown to induce phenotypic changes consistent with EndMT, and HIF1α-induced induction of the transcription factor SNAIL in coronary artery endothelial cells has been identified as potential mechanism linking hypoxia and fibrosis in the heart (288).…”

A current view of G protein-coupled receptor - mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention

“…ED, occurring in failing RV, interconnects with fibrosis, as this appears to be a factor in the decreased capillary density-ED observed in hypertrophy and with the altered metabolism of CM, critical towards HF [217,218] . ED can result in potentially uncontrolled inflammation of local RV tissue and in turn can lead to EC apoptosis, down regulation of eNOS and PGIS.…”

Coronary vascular growth matches IGF‐1‐stimulated cardiac growth in fetal sheep

“…New myocardium requires concomitant establishment of adequate vascular supply, 16 as appropriate coronary vascularity is critical for life‐long function and health 17‐21 . Inadequate coronary supply contributes to angina, cardiac syndrome X, impaired cardiac function, impaired healing, and cellular necrosis and apoptosis.…”