Maturation-Dependent Differences in Regulation of Sarcoplasmic Reticulum Ca2+ ATPase in Sheep Myocardium in Response to Pressure Overload: A Possible Mechanism for Maturation-Dependent Systolic and Diastolic Dysfunction
| Autor: | Israel Mirsky, Alan M Fujii, Lucy W. Arnold, Teruhiko Aoyagi, Seigo Izumo, Michael F. Flanagan |
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| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Systole Diastole Gene Expression Blood Pressure Calcium-Transporting ATPases In Vitro Techniques Biology Left ventricular hypertrophy Calsequestrin Sodium-Calcium Exchanger Muscle hypertrophy Contractility Internal medicine Myosin medicine Animals RNA Messenger Pressure overload Sheep Myocardium Endoplasmic reticulum Hemodynamics Heart medicine.disease Disease Models Animal Sarcoplasmic Reticulum Endocrinology Pediatrics Perinatology and Child Health Calcium Hypertrophy Left Ventricular |
| Zdroj: | Pediatric Research. 50:246-253 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-200108000-00014 |
| Popis: | We have previously demonstrated that pressure-overload hypertrophy in adult sheep is associated with myocardial dysfunction whereas that in young lambs is associated with normal contractility. To probe for possible mechanisms of these age-dependent differences, we assessed mRNA expression of genes encoding critical components of myocardial Ca(2+) handling in the same animal model. We studied left ventricular myocardium of young and adult sheep with short-term (48 h) and long-term (6 wk) pressure overload induced by ascending aortic constriction. Six weeks of pressure overload induced the significant left ventricular hypertrophy (36 and 39% increase in left ventricular/body weight ratio in lambs and sheep, respectively). The Ca(2+) ATPase and Na(+)/Ca(2+) exchanger mRNA decreased with pressure overload only in the adult (p0.05). Ca(2+) channel mRNA was slightly increased by pressure overload regardless of age (p0.05). Calsequestrin, sarcoplasmic reticulum Ca(2+) release channel, or myosin heavy-chain mRNA levels did not significantly differ. In adult sheep after 6 wk of pressure overload, decreases in load-adjusted midwall shortening (systolic dysfunction) and prolongation of relaxation time constant (diastolic dysfunction) correlated with decreases in Ca(2+)-ATPase mRNA. The sarcoplasmic reticulum Ca(2+)-ATPase protein level and Ca(2+) uptake activity of isolated sarcoplasmic reticulum vesicles were depressed only in the adult with pressure-overload hypertrophy but not in the young. We demonstrated age-dependent differences in mRNA expression of Ca(2+)-handling protein genes in response to pressure overload, which preceded the occurrence of hypertrophy and myocardial dysfunction. Thus, altered expression of Ca(2+)-handling protein genes may be one of the primary responses to pressure overload rather than a phenomenon secondary to myocardial hypertrophy. |
| Databáze: | OpenAIRE |
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