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 (PPARdelta) plays beneficial roles in cardiac disorders. However, the relationship between CRP and PPARdelta in cardiac cells remains unclear. This study focused on the underlying molecular mechanisms of CRP and PPARdeltaagonists. Cardiomyocytes and cardiomyoblast cell line (H9c2) were used in different groups: Untreated; 15 microg/ml CRP with or without 1 microM PPARdelta agonists (L-165041). CRP increased PPARdelta and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts. NF-kappaB inducing kinase (NIK) and NF-kappaB 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 PPARdelta expression in cardiomyocytes and H9c2. L-165041 attenuated CRP-induced pro-inflammatory signaling through p38MAPK and c-JNK in H9c2 cardiomyoblasts. However, PPARdelta activation attenuated CRP-induced NF-kappaB pathway may be independent of CD32. These results may provide new evidence of PPARdelta beneficial effects for inflammatory cardiomyopathy.
Liang
Yao-Jen
YJ
Department and Institute of Life Science, Fu-Jen Catholic University, Taipei, Taiwan.
Chen
Chao-Yi
CY
Juang
Shiow-Jen
SJ
Lai
Ling-Ping
LP
Shyu
Kou-Gi
KG
Wang
Bao-Wei
BW
Liu
Shannen Yuan-Chun
SY
Leu
Jyh-Gang
JG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000494:pharmacology / Q000502:physiology*; D009202:Cardiomyopathies / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017930:Genes, Reporter; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008156:Luciferases / Q000235:genetics; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics; D047494:PPAR delta / Q000819:agonists* / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
D015850:Interleukin-6; D016328:NF-kappa B; D047494:PPAR delta; D002097:C-Reactive Protein; D008156:Luciferases