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EXPRESSION OF CARDIOLIPIN BIOSYNTHESIS AND REMODELING ENZYMES IN ADULT HEART FAILURE
Author(s) -
Grudis Jonathan E.,
Chatfield Kathryn C.,
Sparagna Genevieve C.,
Hijmans Jamie,
Sobus Rebecca D.,
Sucharov Carmen C.,
Miyamotto Shelley D.,
Stauffer Brian L.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1085.12
Subject(s) - cardiolipin , heart failure , enzyme , medicine , ventricle , biosynthesis , ventricular remodeling , endocrinology , acyltransferase , citrate synthase , metabolism , cardiomyopathy , mitochondrion , biology , chemistry , biochemistry , phospholipid , membrane
Background Cardiolipin (CL) is a unique phospholipid that is an essential component of the inner‐mitochondrial membrane critical for normal energy metabolism. Biosynthesis of CL occurs via an enzymatic pathway or through remodeling of existing CLs. The content of total CL and (18:2) 4 CL (tetralinoleic form, normally predominant in the heart) are lower in ventricular tissue from adults with heart failure secondary to idiopathic dilated cardiomyopathy (IDC). Purpose The aim of this study was to determine the expression levels of CL biosynthetic and remodeling enzymes associated with CL content changes in IDC. Methods mRNA was isolated from the left ventricle (LV) of adult IDC patients at transplant (n= 27; mean age = 51±14) and non‐failing control LV from donor hearts (n= 15, mean age = 43±8). RT‐PCR was used to measure expression of CL biosynthesis and remodeling enzymes. Results Expression of biosynthetic enzymes, CDP diacylglycerol synthase 2 and phosphatidylglycerolphosphate synthase, were both 33% lower in IDC LV (p<0.05). Remodeling enzymes, monolyso‐CL acyltransferase and tafazzin, were also down‐regulated (66% and 43% respectively, p<0.01) in IDC LV compared to controls. Conclusions These results demonstrate that biosynthetic and remodeling CL abnormalities are present in failing IDC hearts and may contribute to mitochondrial CL abnormalities in heart failure. Supported by NIH/NCATS Colorado CTSI Grant Number UL1 TR000154.