Peroxisome proliferator-activated receptor delta agonists attenuated the C-reactive protein-induced pro-inflammation in cardiomyocytes and H9c2 cardiomyoblasts

C-reactive protein (CRP) has emerged as a new marker for cardiovascular diseases. Activation of peroxisome proliferator-activated receptor delta (PPAR delta) plays beneficial roles in cardiac disorders. However, the relationship between CRP and PPAR delta in cardiac cells remains unclear. This study focused on the underlying molecular mechanisms of CRP and PPAR delta agonists. Cardiomyocytes and cardiomyoblast cell line (H9c2) were used in different groups: Untreated; 15 mu g/ml CRP with or without 1 mu M PPAR delta agonists (L-165041). CRP increased PPAR delta and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts. NF-kappa B inducing kinase (NIK) and NF-kappa B pathway also activated by CRP stimulation. These changes could be inhibited by L-165041 through p38MAPK and c-JNK pathways. However, transfection with siRNA of CD32 CRP receptor did not decrease CRP signaling or reverse the effects of L-165041 in CRP-treated cardiomyocytes and H9c2. Pretreatment with L-165041 attenuated apoptosis induced by hypoxia with or without CRP in H9c2 cardiomyoblasts. CRP up-regulated PPAR delta expression in cardiomyocytes and H9c2. L-165041 attenuated CRP-induced pro-inflammatory signaling through p38MAPK and c-JNK in H9c2 cardiomyoblasts. However, PPAR delta activation attenuated CRP-induced NF-kappa B pathway may be independent of CD32. These results may provide new evidence of PPAR delta beneficial effects for inflammatory cardiomyopathy. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.