Suppression of graft coronary artery disease by a brief treatment with a selective epsilonPKC activator and a deltaPKC inhibitor in murine cardiac allografts

Circulation
Masashi TanakaRobert C Robbins

Abstract

Inhibiting delta protein kinase C (deltaPKC) during reperfusion and activating epsilon PKC (epsilonPKC) before ischemia each limits cardiac ischemic injury. Here, we examined whether limiting ischemia-reperfusion injury inhibits graft coronary artery disease (GCAD) and improves murine cardiac allografting. Hearts of FVB mice (H-2q) were transplanted into C57BL/6 mice (H-2b). epsilonPKC activator (psiepsilonRACK) was injected intraperitoneally (20 nmol) into donor mice 20 minutes before procurement. Hearts were then perfused with psiepsilonRACK (1.5 nmol) through the inferior vena cava (IVC) and subsequently submerged in psiepsilonRACK (0.5 micromol/L) for 20 minutes at 4 degrees C. Before reperfusion, the peritoneal cavity of recipients was irrigated with deltaPKC inhibitor (deltaV1-1, 300 nmol); control animals were treated with normal saline. The total ischemic time to the organ was 50 minutes. Two hours after transplantation, production of inflammatory cytokines and adhesion molecules, cardiomyocyte apoptosis, and caspase-3 and caspase-9 (but not caspase-8) activities were significantly reduced in the PKC regulator-treated group. Fas ligand levels (but not Fas) were also significantly reduced in this group. Importantly, GCAD...Continue Reading

Citations

Mar 3, 2006·Current Atherosclerosis Reports·Amandeep Dhaliwal, Vinay Thohan
Dec 1, 2012·Nature Reviews. Drug Discovery·Daria Mochly-RosenKevin V Grimes
Apr 14, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Akira MimaGeorge L King
Dec 25, 2010·Journal of Cardiovascular Pharmacology and Therapeutics·Richard Qinxue DingWei Zhou
Dec 6, 2008·Trends in Endocrinology and Metabolism : TEM·Eric N ChurchillDaria Mochly-Rosen
May 6, 2016·American Journal of Physiology. Renal Physiology·Anita T Layton
Nov 18, 2014·Biochemical Society Transactions·Nir Qvit, Daria Mochly-Rosen
Sep 20, 2012·European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery·Antonio D LassalettaFrank W Sellke
Feb 17, 2018·Biochemical Pharmacology·Zhongwei Liu, Raouf A Khalil

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