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Interaction of Obesity and Hypertension on Cardiac Metabolic Remodeling and Survival Following Myocardial Infarction.


ABSTRACT: Background Obesity and hypertension are risk factors for myocardial infarction (MI); however, their potential interactions on post-MI outcomes are unclear. We examined interactions of obesity and hypertensionon post-MI function, remodeling, metabolic changes, and recovery. Methods and Results Male and female C57BL/6J mice were provided standard chow or high-fat/fructose diet for 8 weeks and then infused with angiotensin II for 2 weeks to induce hypertension. MI was then induced by surgical ligation of the left coronary artery for 7 days. Obesity alone did not cause cardiac injury or exacerbate hypertension-induced cardiac dysfunction. After MI, however, obese-normotensive mice had lower survival rates compared with chow-fed mice (56% versus 89% males; 54% versus 75% females), which were further decreased by hypertension (29% males; and 35% females). Surviving obese-normotensive males displayed less left ventricular dilation and pulmonary congestion compared with chow-fed males after MI; hypertension reversed left ventricular dilation because of high-fat/fructose diet and promoted significant pulmonary congestion compared with chow-fed controls. Obese-normotensive males displayed higher left ventricular α-MHC (alpha-myosin heavy chain) protein, phosphorylated Akt (protein kinase B) and AMPK (adenosine-monophosphate activated kinase), PPAR-γ (peroxisome proliferator activated receptor gamma), and plasma adiponectin levels after MI, indicating favorable contractile and metabolic changes. However, these favorable contractile and metabolic changes were attenuated by hypertension. Obese-hypertensive males also had lower levels of collagen in the infarcted region, indicating decreased ability to promote an adaptive wound healing response to MI. Conclusions Obesity reduces post-MI survival but is associated with improved post-MI cardiac function and metabolism in surviving normotensive mice. When hypertension accompanies obesity, favorable metabolic pathways associated with obesity are attenuated and post-MI cardiac function and remodeling are adversely impacted.

SUBMITTER: Mouton AJ 

PROVIDER: S-EPMC8174210 | biostudies-literature |

REPOSITORIES: biostudies-literature

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