Study of autocamtide 2-related inhibitory peptide prevent cardiac fibroblasts excreting cytokines and expressing matrix metalloproteinases

Abstract

Abstract: AIM: To observe the role of calcium calmodulin dependent protein Kinase(CaMK) Ⅱinhibitor(autocamtide 2-related inhibitory peptide, AIP) in rat cardiac fibroblasts proliferation and their molecular mechanism. METHODS: Using cultured cardiac fibroblasts from neonatal 1-3 days rat (3 generation); This cells were divided into five groups as follows :control group, AngⅡ group(0.1 μmol/L), AngⅡ(0.1 μmol/L)+AIP group(0.2 μmol/L), AngⅡ(0.1 μmol/L))+AIP group(0.5 μmol/L), AngⅡ(0.1 μmol/L)+AIP group(1.0 μmol/L); The cardiac fibroblasts proliferation was detected by cell counting and MTT; The cytokines excreting(TGF-β₁, TNF-a) was investigated by ELISA. The expression of MMP-2,9 mRNA was detected by RT-PCR. RESULTS: AIP (0.5 μmol/L,1.0 μmol/L) could prevent cardiac fibroblasts proliferation induced by angiotensin Ⅱin a dose-dependent manner; AIP (0.5 μmol/L,1.0 μmol/L) could prevent cytokines excreting induced by angiotensin Ⅱin a dose-dependent manner; AIP (0.5 μmol/L, 1.0 μmol/L) could prevent the increasing expression of MMP-2,9 mRNA and MMP-2,9 protein expression induced by 0.1 μmol/L AngⅡ. CONCLUSION: AIP(0.5 μmol/L, 1.0 μmol/L) could prevent myocardial fibrosis induced by angiotensin Ⅱ; The probably mechanism was that: AIP could prevent cardiac fibroblasts proliferation,its cytokines excreting and regulate extracellular matrix(MMP-2、9).

Key words: Cardiac fibroblasts, Angiotensin Ⅱ, Calcium calmodulin dependent protein KinaseⅡ, autocamtide 2-related inhibitory peptide, Matrix metalloproteinases-2,9

CLC Number:

R542.2
R969

ZHONG Yong-jun, CHEN Dong-qin, YAO Xiao-yan. Study of autocamtide 2-related inhibitory peptide prevent cardiac fibroblasts excreting cytokines and expressing matrix metalloproteinases[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(4): 422-428.

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