Study on cardiac hypertrophy and failure by lipid storage

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Primary systemic carnitine deficiency is an autosomal recessive disorder caused by a decreased renal re-absorption of carnitine due to mutations of the carnitine transporter OCTN2 gene, and is associated with hypertrophic cardiomyopathy. Heterozygotes may be at risk for cardiomyopathy in the presence of additional risk factors such as hypertension. We investigated the effects of surgically-induced pressure overload on the hearts of heterozygous mutants of a murine model of systemic carnitine deficiency, juvenile visceral steatosis mouse (jvs/+). At baseline, there were no differences in physical characteristics between WT and jvs/+ mice. However, plasma and myocardial total carnitine levels in jvs/+ mice were lower than in WT mice. Both WT and jvs/+ mice were subjected to ascending aortic constriction (AAC) with or without 1% L-carnitine supplementation. After AAC, (jvs/+)-AAC mice showed an exaggeration of cardiac hypertrophy and pulmonary congestion, reduced myocardial phosphocreatine-to-ATP ratio, and increased mortality compared with WT-AAC mice ; L-carnitine supplementation prevented these changes in (jvs/+)-AAC mice. Cardiomyopathy and heart failure with energy depletion may be induced by pressure overload in heterozygotes of OCTN2 mutations and could be prevented by L-carnitine supplementation.