Elamipretide restores protein and mrna expression levels of cardiolipin synthase-1 in left ventricular myocardium of dogs with chronic heart failure
Gupta RC, Singh-Gupta V, Zhang K, Xu J, Sabbah HN. Elamipretide restores protein and mrna expression levels of cardiolipin synthase-1 in left ventricular myocardium of dogs with chronic heart failure. J Am Coll Cardiol. 2018;71(11)
Background: Cardiolipin (CL), an inner mitochondrial (MITO) membrane phospholipid is synthesized by CL synthase-1(CLS1) and is critical for normal MITO function. Levels of CL are reduced in MITO of LV myocardium of dogs with heartfailure (HF) and are normalized after chronic therapy withelamipretide (ELAM), a novel, MITO targeting peptide. Objective: This study examined the effects of chronictherapy with ELAM on protein and mRNA levels of CLS1 inLV myocardium of dogs with coronary microembolizations-induced HF (LVEF ∼30%). Methods: LV tissue from 14 HF dogs randomized to 3 months therapy with s.c. injections ofELAM (0.5 mg/kg once daily, n=7) or saline (control, CON, n=7) and LV tissue from 6 normal (NL) dogs was used. Protein levels of CLS1 and porin (an internal control), were determined in LV tissue extract by Western blotting coupled with chemiluminescence and band intensities expressed indensitometric units (du). mRNA expression of CLS1 normalized to GAPDH, was measured in RNA from LV tissue using real-time PCR and expressed as fold change from NL. Results: Levels of porin and GAPDH were unchanged among study groups. mRNA and protein levels of CLS1 were decreased signifcantly in HF-CON compared to NL dogs. Treatment with ELAM (HF+ELAM) normalized CLS1 mRNAand protein expression. Conclusion: mRNA and proteinlevels of CLS1 are decreased in LV of HF dogs and are normalized after chronic therapy with ELAM. The finding points to a mechanism for the observed normalization of CL after chronic ELAM therapy.