Heart failure preventive induces heart failure in mice

Photo courtesy of Cardiomegaly

Who says too much growth and nutrition is a bad thing? The human heart does first and foremost. Past research has set out to prove limiting the amount of fatty acid derivative entering the mitochondria of the heart is protective in that it prevents cardiac hypertrophy and heart failure. However, researchers of the Sanford-Burnham Medical Research Institute believe carnitine palmitoyltransferase 1 (CPT1) inhibition (lowered ß-oxidation) actually exacerbates cardiac hypertrophy and induces heart failure. This study proved their assumptions correct using CPT1b+/- knockout mice.

CPT1b is the main isoform of CPT1 found in the heart and works to assist long chain acetyl-CoA’s (from fatty acid metabolism) entrance into the mitochondria for ß-oxidation. ß-oxidation is an important contributor of energy to the heart as so is glucose oxidation (70:30 energy contribution).

Cardiac hypertrophy is a thickening of the heart resulting in a decrease in the volume of its chambers. This can occur naturally in athletes or due to a physiological impairment in non-athletes.

In this study, CPT1b+/- mice were subjected to transverse aorta constriction (TAC) induced pressure-overload and analyzed for accompanying cardiac problems. Basically cardiac thickening was forced on the wild type/control mice and the CPT1b+/- mice.

At baseline, no cardiac abnormalities was seen in either mouse cohort. After inducing TAC, most CPT1b+/- mice died after two weeks, while their wild type companions survived. Additionally, higher rates of cardiomyocyte (heart cell) apoptosis was seen in the knockout mice than wild type. Following, triglyceride levels were measured in the post-mortem hearts of mice. Again, the  CPT1b+/- mice showed higher levels of lipids (Oil-red-O staining) than the normal mice.

CPT1b deficiency in hearts has been shown to exacerbate hypertrophy and heart failure, increase cellular suicide, and raise lipotoxicity. Therefore, caution should be taken with clinical prescription of drugs inhibiting cardiac CPT1.

Reference:
Lan He, Teayoun Kim, Qinqiang Long, Jian Liu, Peiyong Wang,Yiqun Zhou, Yishu Ding, Jeevan Presain, Philip A. Wood, Qinling Yang. Carnitine Palmitoyltransferase-1b (CPT1b) Deficiency Aggravates Pressure-Overload-Induced Cardiac Hypertrophy due to Lipotoxicity. DOI: 10.1161/CIRCULATIONAHA.111.075978
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484985/

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