Ascending aortic banding in rats (n=68) induced moderate eccentric remodeling associated with impaired mitochondrial function, enhanced autophagy/apoptosis, and altered calcium handling.
Does pressure overload-induced left ventricular remodeling alter mitochondrial homeostasis and calcium handling in Sprague Dawley rats?
In a rat model of pressure overload, the transition from concentric to moderate eccentric left ventricular remodeling is associated with impaired mitochondrial function, enhanced autophagy/apoptosis, and altered calcium handling before overt systolic dysfunction occurs.
BACKGROUND: Following pressure overload, compensatory concentric left ventricular remodeling (CR) variably transitions to eccentric remodeling (ER) and systolic dysfunction. Mechanisms responsible for this transition are incompletely understood. Here we leverage phenotypic variability in pressure overload-induced cardiac remodeling to test the hypothesis that altered mitochondrial homeostasis and calcium handling occur early in the transition from CR to ER, before overt systolic dysfunction. METHODS AND RESULTS: Sprague Dawley rats were subjected to ascending aortic banding, (n=68) or sham procedure (n=5). At 3 weeks post-ascending aortic banding, all rats showed CR (left ventricular volumes < sham). At 8 weeks post-ascending aortic banding, ejection fraction was increased or preserved but 3 geometric phenotypes were evident despite similar pressure overload severity: persistent CR, mild ER, and moderate ER with left ventricular volumes lower than, similar to, and higher than sham, respectively. Relative to sham, CR and mild ER phenotypes displayed increased phospholamban, S16 phosphorylation, reduced sodium-calcium exchanger expression, and increased mitochondrial biogenesis/content and normal oxidative capacity, whereas moderate ER phenotype displayed decreased p-phospholamban, S16, increased sodium-calcium exchanger expression, similar degree of mitochondrial biogenesis/content, and impaired oxidative capacity with unique activation of mitochondrial autophagy and apoptosis markers (BNIP3 and Bax/Bcl-2). CONCLUSIONS: After pressure overload, mitochondrial biogenesis and function and calcium handling are enhanced in compensatory CR. The transition to mild ER is associated with decrease in mitochondrial biogenesis and content; however, the progression to moderate ER is associated with enhanced mitochondrial autophagy/apoptosis and impaired mitochondrial function and calcium handling, which precede the onset of overt systolic dysfunction.
Chaanine et al. (Fri,) conducted a other in Pressure overload-induced left ventricular remodeling (n=73). Ascending aortic banding vs. Sham procedure was evaluated on Mitochondrial homeostasis, calcium handling, and left ventricular remodeling phenotypes. Ascending aortic banding in rats (n=68) induced moderate eccentric remodeling associated with impaired mitochondrial function, enhanced autophagy/apoptosis, and altered calcium handling.
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