Alterations in the expression of myosin heavy chain isoforms in hypoxia-induced hypertrophied ventricles in rats.
This study was designed to characterize cardiac changes in myosin heavy chain (MHC)-beta, capacity for oxidative metabolism and muscle mass in hearts of rats born and raised at simulated altitudes (2200 m or 4000 m) compared to age-matched sea level controls. On the basis of electrophoretic analyses, we found that the hypoxia-induced ventricular hypertrophy produces a significant increase in MHC-beta in both ventricles. Furthermore, we observed an exponential relationship between the mass of right ventricular muscle and percentages in the expression of MHC-beta (r=0.928, P<0.001). We also observed the reduction in the citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD) activities in both hypertrophied ventricles (P<0.001). As a consequence, there were negative correlations between the percentage expression of MHC-beta and the CS or HAD activities (P<0.001). In contrast, there were no significant correlations between the relative expressions of MHC-beta and either CS or HAD enzymatic activities in both ventricles after adjusting for the relative wet mass. In conclusion, the observed increases in MHC-beta may be a compensation to augment efficiency if muscles contract in hypertrophied hearts where mitochondria fail to respond to increases in tissue mass. These findings suggest that the increased relative expression of MHC-beta is a compensation to sustain cardiac contractile efficiency in response to impaired oxidative metabolism in the hypoxia-induced hypertrophied ventricles of rats.
Hashimoto
Takeshi
T
Department of Environmental Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Yoshida, Sakyo-Ku, Kyoto 606-8501, Japan.
Yamasaki
Sakiya
S
Taguchi
Sadayoshi
S
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000222:Adaptation, Physiological; D000531:Altitude; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000737:chemistry / Q000201:enzymology; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000378:metabolism; D000860:Hypoxia; D008297:Male; D018995:Myosin Heavy Chains / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D024501:Nonmuscle Myosin Type IIB; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar; D016276:Ventricular Function
C000594638:MYH7 protein, rat; D020033:Protein Isoforms; D015094:3-Hydroxyacyl CoA Dehydrogenases; D002950:Citrate (si)-Synthase; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains