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Patrick Assayag, Danièle Charlemagne, Isabelle Marty, Joël de Leiris, Anne Marie Lompré, François Boucher, Paul-Etienne Valère, Sylviane Lortet, Bernard Swynghedauw, Sophie Besse, Effects of sustained low-flow ischemia on myocardial function and calcium-regulating proteins in adult and senescent rat hearts, Cardiovascular Research, Volume 38, Issue 1, April 1998, Pages 169–180, https://doi.org/10.1016/S0008-6363(97)00283-6
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Abstract
Objective: Both aging and myocardial ischemia are associated with alterations of calcium-regulating proteins. We investigated the effects of graded levels of low-flow ischemia on myocardial function and on SR Ca2+-ATPase (SERCA2), Na+-Ca2+ exchanger (NCx) and ryanodine receptor (RyR2), at mRNA and protein levels in both adult and senescent myocardium. Methods: Isolated hearts from 4 and 24 month old (mo) rats were retrogradely perfused during 180 min at 100% (100% CF, n=11 and n=11 respectively), 30% (30% CF, n=10 and n=12) or 15% (15% CF, n=13 and n=8) of their initial coronary flow, and active tension and coronary resistance (in % of their baseline value) were recorded. After 180 min of perfusion, NCx, RyR2 and SERCA2 mRNAs (in % of age-matched 100% CF group value) and protein levels were quantitated in the left ventricles by slot blot and Western blot analysis, respectively. Results: In 24 mo hearts, low-flow ischemia induced a greater fall in active tension (−65±7% vs. −40±4% in 4 mo 30% CF, p<0.01 and −82±2% vs. −60±5% in 4 mo 15% CF groups, p<0.05 after 15 min of ischemia) and a greater increase in coronary resistance (+357±44% vs. +196±39% in 4 mo 30% CF, p<0.05 and +807±158% vs. +292±61% in 4 mo 15% CF groups, p<0.001 after 15 min of ischemia). An increased accumulation of SERCA2 (+36%) and NCx (+46%) transcripts, but not RyR2, already occurred in 24 mo 30% CF group while the 3 transcripts accumulated in 24 mo 15% CF group. In 4 mo rats SERCA2 (+26%), NCx (+35%) and RyR2 (+81%) mRNA levels only increased in the 15% CF group. Corresponding calcium-regulating protein levels were unaltered whatever the degree of flow reduction in both 4 mo and 24 mo hearts. Conclusion: Low-flow ischemia does not induce calcium-regulating protein loss in both adult and senescent hearts. The increase in mRNAs coding for calcium-handling proteins and the impairment of myocardial function which occur at a lesser degree of coronary flow reduction in senescent hearts, indicate a higher vulnerability to low-flow ischemia during aging.
