Expression of Cardiolipin Biosynthesis and Remodeling Enzymes in Adult Heart Failure

Abstract

Purpose Cardiolipin (CL) is a unique phospholipid that is an essential component of the inner-mitochondrial membrane (IMM) and is critical to normal energy metabolism. In the heart, CL exists predominantly in the tetralinoleic form, (18:2) 4CL, which has the greatest affinity for the IMM and protection against cellular apoptosis. Biosynthesis of CL occurs by means of a five-step enzymatic pathway. Tetralinoleic CL is formed by the remodeling of existing CL. Total CL content is lower in ventricular tissue from adult humans with idiopathic dilated cardiomyopathy (IDC). Purpose: The aim of this study was to determine which mitochondrial CL biosynthetic and linoleic remodeling enzyme levels are dysregulated in adult IDC. Methods and Materials mRNA was isolated from failing adult left ventricle (LV) of patients with IDC obtained at the time of transplant (n=27; mean age = 51±14) and non-failing control LV from donor hearts not implanted for technical reasons (n=15, mean age = 43±8). RT-PCR was employed to measure gene expression of CL biosynthesis and (18:2) 4CL remodeling enzymes. Results In the biosynthesis pathway we found 37% lower CDP diacylglycerol synthase 2 and 35% lower phosphatidylglycerolphosphate synthase (both P Conclusions These results demonstrate that biosynthetic and remodeling CL abnormalities are present in the IDC adult failing heart and may contribute to mitochondrial CL abnormalities in heart failure. Future investigations will compare enzymatic dysregulation between these adult groups with pediatric IDC samples for potential age-related patterns in dysregulation. Ultimately, we hope to elucidate mechanisms of CL dysregulation and targets for pharmacological therapy.