Epidemiological studies support an independent inverse association between high-density\nlipoprotein (HDL) cholesterol levels and heart failure incidence. The effect of selective HDL-raising\nadeno-associated viral serotype 8-human apolipoprotein (apo) A-I (AAV8-A-I) gene transfer on\ncardiac remodeling induced by transverse aortic constriction (TAC) was evaluated in C57BL/6\nlow-density lipoprotein receptor-deficient mice. Septal wall thickness and cardiomyocyte\ncross-sectional area were reduced by 16.5% (p < 0.001) and by 13.8% (p < 0.01), respectively,\neight weeks after TAC in AAV8-A-I mice (n = 24) compared to control mice (n = 39). Myocardial\ncapillary density was 1.11-fold (p < 0.05) higher and interstitial cardiac fibrosis was 45.3% (p < 0.001)\nlower in AAV8-A-I TAC mice than in control TAC mice. Lung weight and atrial weight were\nsignificantly increased in control TAC mice compared to control sham mice, but were not increased\nin AAV8-A-I TAC mice. The peak rate of isovolumetric contraction was 1.19-fold (p < 0.01) higher\nin AAV8-A-I TAC mice (n = 17) than in control TAC mice (n = 29). Diastolic function was also\nsignificantly enhanced in AAV8-A-I TAC mice compared to control TAC mice. Nitro-oxidative stress\nand apoptosis were significantly reduced in the myocardium of AAV8-A-I TAC mice compared\nto control TAC mice. In conclusion, selective HDL-raising human apo A-I gene transfer potently\ncounteracts the development of pressure overload-induced cardiomyopathy.
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