Changes in myosin heavy chain and its localization in rat heart in association with hypobaric hypoxia-induced pulmonary hypertension
Tokyo Women's Medical University, Edo, Tokyo, Japan The Journal of Pathology
(Impact Factor: 7.43).
07/2002; 197(3):380-7. DOI: 10.1002/path.1132
Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart. In rat cardiac ventricles, pressure and volume overload are well known to be associated with changes in cardiac myosin heavy chain (MHC) isoforms. To study the effects of HHE on the MHC profile in the ventricles, 83 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1-8 weeks. Pulmonary arterial pressure, right ventricular free wall (RVFW) weight, the ratio of RVFW weight over body weight (BW), the ratio of left ventricular free wall (LVFW) weight over BW, and myocyte diameter in both ventricles showed significant increases after 1 week, 2 weeks, 1 week, 6 weeks, and 4 weeks of HHE, respectively. Semi-quantitative reverse transcriptase-polymerase chain reaction revealed that beta-MHC mRNA expression was increased significantly in both ventricles at 6 and 8 weeks of HHE, whereas alpha-MHC mRNA expression was decreased significantly at 6 and 8 weeks of HHE in the right ventricle (RV) and at 6 weeks of HHE in the left ventricle (LV). The percentage of myosin containing the beta-MHC isoform was increased significantly at 4-8 weeks of HHE in RV and at 6 weeks of HHE in LV. In situ hybridization showed that the area of strong staining for beta-MHC mRNA was increased in both ventricles at 8 weeks of HHE, and showed a decrease from RVFW to cardiac septum, and from cardiac septum to LVFW. These results suggest that HHE has a significant effect on the expression of both MHC mRNA and protein in the heart, particularly in RV. These changes may reflect a role for cardiac MHC in the response to pulmonary hypertension in HHE.
Available from: Christophe M R LeMoine
- "Environmental factors such as hypoxia can increase cardiac workload by causing an elevation in intraventricular pressure in the right ventricle, due to pulmonary vasoconstriction that aids increased perfusion of the lungs  . Thus, pulmonary hypertension leads to pressure-overloaded hypertrophy of the right ventricle    , but there is usually no change in systemic arterial pressure, nor any left ventricular hypertrophy  . On the other hand, chronic cold exposure typically causes volume-overloaded hypertrophy of both ventricles  . "
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ABSTRACT: In mammals, environmental challenges often result in physical and metabolic cardiac remodeling (i.e., hypertrophy and a shift from lipid to carbohydrate oxidation). While chronic hypoxia and cold are both known to elicit cardiac changes, little is known about their combined effects.
To investigate the cumulated effects of these two stressors on cardiac physiology, CD-1 mice were exposed for 4 weeks to normoxia/normothermia, hypoxia, cold, or combined hypoxic-cold. We assessed physical characteristics, left ventricular activities of fatty acid catabolic enzymes short-chain β-hydroxyacyl-CoA dehydrogenase (SCHAD) and medium-chain acyl-CoA dehydrogenase, and mRNA levels of Acadm, muscle- and liver-type carnitine palmitoyltransferase (Cpt-1β, Cpt-1α), and the transcriptional regulator PPARα.
1) Chronic hypoxia reduced SCHAD activity without physical remodeling or mRNA changes; 2) chronic cold lead to reduced SCHAD activity in hypertrophied left ventricles and lowered right ventricular Cpt-1α mRNA (compared to chronic hypoxia); and 3) despite causing hypertrophy of both ventricles, chronic exposure to combined hypoxic-cold did not induce significant metabolic remodeling.
In response to environmental challenges, cardiac muscles 1) show distinct physical and metabolic remodeling, 2) respond to two stressors simultaneously but not additively, and 3) maintain an adult metabolic phenotype with long-term exposure to environmentally realistic hypoxic-cold.
- "In an autopsy study of a patient died of Monge's disease, marked hypertrophy of the right ventricle of the heart, multiple derangement and morphological alterations of the pulmonary vasculature were observed. The major cause of death was cardiac insufficiency due to chronic cor pulmonale (Porter and Knight, 1971) suggesting the chronic effects of mal-adaptation to hypoxia can be lethal with pulmonary hypertension and cardiac malfunction (Nakanishi et al., 2002). Clinically, hypoxia can be due to shortage of blood supply delivered to the body tissues. "
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ABSTRACT: Right ventricular hypertrophy and right heart failure occur in patients with pulmonary hypertension. The mechanisms of left
ventricular hypertrophy are well understood, however, information on right ventricular hypertrophy is limited. Studies of
embryonic and adult hearts provided evidence that the molecular signaling mechanisms are different for right and left ventricles.
Thus, the development of therapeutic strategies specific for the right heart is needed. This chapter summarizes current understanding
of cell growth signaling mechanisms in the right ventricle.
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