Abstract 082: Deletion of Mitochondrial Aldehyde Dehydrogenase 2 Restrains Cardiac Fatty Acid Oxidation during Pressure-Overload Induced Heart Failure
Rationale: Mitochondrial Aldehyde dehydrogenase 2 (ALDH2) is regarded as an inner protector of cardiac diseases, which downregulation has been reported to induce cardiac metabolic remodeling and augmented glucose uptake. However, it has not been investigated whether myocardial fatty acid oxidation (FAO) could be regulated by ALDH2.
Objective: We hypothesized that global deletion of ALDH2 would deteriorate heart function and energy generation, inhibit cardiac FAO and promote the development of pressure-overload induced heart failure.
Methods and Results: ALDH2 knockout (ALDH2-/-) did not led to considerable birth defects and cardiac dysfunction in base line. Pressure overload were induced by transverse aortic constriction (TAC) for 4weeks. In echocardiographic and hemodynamic test, left ventricular systolic functions were decreased in ALDH2-/- TAC mice compared with wild type (WT) TAC mice. Myocardial morphology and subcellular structure examinations shown ALDH2-/- TAC mice exhibited cardiac hypertrophy with a significant mitochondrial destroy relative to WT-TAC. Meanwhile, a decreased FAO and ATP production were detected (54±3.6% and 77±1.5%, p<0.05,respectively) in ALDH2-/- sham myocardium, which were aggravated by pressure overload. Therefore, ALDH2 deletion accelerated cardiac energy remolding. Furthermore, ALDH2-/- repressed AMP-activated protein kinase (AMPK) phosphorylation(49±4.6%, p<0.05) and subsequently inhibited the activation of peroxisome proliferator-activated receptor a (PPARa) (31±2.9%, p<0.05) - carnitine palmitoyl transferase 1 (CPT1) (81.5±5.2%, p<0.05) - fatty acid transportation pathway, which induced inefficient of FAO.
Conclusions: These data of present study suggest that ALDH2 deficiency promotes heart failure and cardiac metabolic remodeling by inhibiting myocardial FAO through AMPK-PPARa-CPT1 pathway.
- © 2013 by American Heart Association, Inc.