INTRODUCTION : In dilated cardiomyopathy (DCM) patients, elevated circulating asymmetric-dimethylarginine (ADMA) concentration is well-established, however the underlying mechanism(s) for excess ADMA is unclear. Reduced circulating nicotinamide-adenine-dinucleotide (NAD+) and sirtuin1 (sirt1) mRNA expression in peripheral blood of DCM patients have been reported; whether this down-regulation influences LVEF (left-ventricular-ejection-fraction) is uncertain.
OBJECTIVE : To investigate whether the expression of cardiac genes (protein arginine methyltransferase1, PRMT1 and sirt1) and circulating analytes (ADMA and NAD+) are altered in peripheral blood and if such changes are associated with LVEF in DCM.
METHODOLOGY : Peripheral blood cells (PBCs) and plasma were isolated from sixty DCM patients. Based on LVEF, patients were categorized as moderate- or severe-left ventricular dysfunction (LVD). Gene expression was determined by quantitative reverse-transcription-polymerase-chain-reaction. Quantification of analytes was assessed by reverse-phase high-performance-liquid-chromatography.
RESULTS : In patients with severe LVD, PRMT1 mRNA and circulating ADMA were higher, while sirt1 mRNA expression and circulating NAD+ were reduced, than moderate LVD. Positive correlation exists between PRMT1 expression- and ADMAversus decreasing LVEF. Whereas reduced sirt1 expression and NAD+ were negatively correlated with decreasing LVEF.
CONCLUSION : As disease severity increases, mRNA expression of two cardiac genes and circulating concentrations of analytes were altered, possibly reflecting stress response effects. This study shows that PBCs-signatures of arginine methylation and cardio-protection can be defined for LVEF and that the peripheral blood mRNA expressions could predict LVD.