Different Biventricular Remodelling of Myosin and Collagen in Pulmonary Hypertension

Abstract

1. To clarify the metabolism of contractile and non-contractile proteins of the ventricles during the development of right ventricular hypertrophy (RVH) and accompanying congestive heart failure (CHF) in response to a pressure overload, monocrotaline was injected subcutaneously into Sprague-Dawley (SD) rats. Myosin isoenzymes (MIE) were analysed by pyrophosphate gel electrophoresis under non-dissociating conditions. Acid-soluble collagens were analysed by an improved, noninterrupted sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Tissue collagen content was also measured after the estimation of hydroxyproline concentration in tissues. 2. Monocrotaline induced RVH, but not left ventricular hypertrophy, at 2 weeks after the injection of monocrotaline, with severe RVH with CHF present at 4 weeks. In the right ventricles (RV) treated with monocrotaline, MIE shifted significantly from V1 to V3 at 2 weeks. The shift of MIE was more pronounced at 4 weeks. The proportion of type III collagen increased significantly compared with controls at 2 weeks. At 4 weeks, the proportion of types III and V collagens increased significantly compared with controls. 3. In left ventricles (LV) treated with monocrotaline, a similar but less remarkable shift of MIE was observed without remodelling of collagen types at 2 and 4 weeks. The concentration of collagen in either the RV or LV treated with monocrotaline showed no significant changes at 2 and 4 weeks compared with controls. 4. These results demonstrate a remodelling of the contractile and non-contractile proteins during the development of RVH and accompanying CHF, and provide evidence for changes in protein metabolism of the counterpart of RV (i.e. the LV). These results may provide important insights into the pathophysiology of adaptive or non-adaptive cardiac hypertrophy in response to a pressure overload.

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

“…MCT-treated rats presented myosin heavy-chain isoform switch in the LV myocardium. The slower b-isoform was increased in the LV of both MCT-4 and MCT-6, as previously reported in different models of RV hypertrophy [17,43,46,47]. Changes in the expression of enzymes involved in bioenergetics and cell metabolism such as pyruvate dehydrogenase kinase-4, acetyl-CoA dehydrogenase and mitochondrial ATP synthase [42,43] as well as a reduced capillary proliferation [21] have also been described in the LV of PH rats.…”

Right Ventricular Failure Following Chronic Pressure Overload Is Associated With Reduction in Left Ventricular Mass

“…This was associated with LV myocyte shrinkage, increased ANP mRNA expression, and diminished ␣-MHC and SERCA2 mRNA expression. Such a fetal gene expression profile was previously observed in the LV of MCT rats (33,37), and rats that developed RVF after chronic pulmonary artery banding (38). Of note, these changes in expressions of ANP, ␣-MHC, and SERCA were not predominant in the LV.…”

Myocardial dysfunction and neurohumoral activation without remodeling in left ventricle of monocrotaline-induced pulmonary hypertensive rats

“…Chronic ET-1 overactivity in heart disease has been associated with slower relaxation and impaired contractility through dysfunctional Ca 2ϩ homeostasis and myosin heavy chain (MHC) isoform switch (10,13,26,28). Curiously, the LV of rats with PH induced by either MCT (11) or hypoxia (32) undergoes MHC isoform switch, whereas ET A receptor antagonists have noticeably been reported to partly prevent this switch in MCT RV myocardium (10). The acute effects of ET A blockade were studied in vitro to ascertain whether there was a functional change in the acute myocardial effects of endogenous ET-1.…”