Abstract
We investigated biochemical and structural changes in collagen in ventricles in right ventricular hypertrophy (RVH) induced by monocrotaline injection in Sprague-Dawley rats. Rats injected with monocrotaline showed significant RVH after 2 weeks compared with the vehicle-treated rats (controls). After 4 weeks, the monocrotaline-treated rats showed severe RVH with heart failure. After 2 weeks, the proportion of type III collagen in the right ventricles (RV) of the monocrotaline-treated rats increased significantly compared with controls, with a concomitant decrease in type I collagen. After 4 weeks, there was a significant increase in the proportion of type III and type V collagens in the RV. In the left ventricles (LV), the proportion of collagen types was similar in the monocrotaline-treated and control rats at 2 and 4 weeks. There was no significant difference in collagen concentration (% collagen in dry defatted tissue) between the monocrotaline-treated rats and controls at either 2 or 4 weeks in the LV and RV. Scanning electron microscopy revealed that the collagen fibrillar sheaths around the myocytes in the endomysium of the RV had thickened and formed a dense network in the monocrotaline-treated rats. In the perimysium, tendon-like collagen fibers increased and became thicker than those in the RV of controls. Giant coiled perimysial fibers were also observed in the monocrotaline-treated RV. These structural changes were more pronounced after 4 weeks of monocrotaline-treatment: Loss of myocytes was evident and was accompanied by replacement fibrosis, where dense collagen fibers aggregated parallel to the long axes of the myocytes. Our results show that biochemical and structural remodeling of collagen occurred in the RV but not in the LV during the development of RVH and heart failure, providing important clues to the pathogenesis and pathophysiology of RVH and cardiac failure in response to pressure overload.
