RT Journal Article
SR Electronic
T1 e0358 Profibrotic influence of high glucose on human cardiac fibroblast functions
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP A111
OP A111
DO 10.1136/hrt.2010.208967.358
VO 96
IS Suppl 3
A1 Jufang Chi
A1 Hangyuan Guo
A1 Fang Peng
A1 Biao Yang
A1 Longbin Liu
A1 Hiroyasu Uzui
YR 2010
UL http://heart.bmj.com/content/96/Suppl_3/A111.3.abstract
AB Aims Recent studies have demonstrated an important role of chronic high glucose concentration for collagen deposition in fibroblasts. However, little is known about the action of angiotensin II type 1 recepter blocker and inflammatory cytokines on ACE inhibitor on matrix metalloproteinase (MMP) regulation and collagen synthesis in human cardiac fibroblasts. In this article, we determined the influence of chronic high glucose concentration on human cardiac fibroblasts functions and the effects of 606A and imidaprilat in these responses. Methods and results Human cardiac fibroblasts were long-time exposure in normal or high glucose media in the absence or presence of 606A or imidaprilat. We have determined their MMP-2 activities by using in-gel zymography. In addition, the collagen IV synthesis was evaluated by the means of ELISA. Results show that chronic high glucose concentration inhibits the activity of MMP-2 and accelerates collagen IV synthesis. When Equimolar mannitol was used as an osmotic control, the activity inhidition of MMP-2 were also observed, however, it is not as strong as that by using high glucose. Inhibition of MMP-2 activity and enhancement of collagen IV synthesis were reserved incompletely by 606A. But complete reservation of MMP-2 activity and collagen IV synthesis was observed by using imidaprilat in cultured media in the experiments. Conclusions Chronic high glucose inhibits the activity of MMP-2 and increases collagen IV synthesis by means of regulating MMP-2 mRNA expression in human cardiac fibroblasts through osmotic and non-osmotic pathways. Inhibition of MMP-2 activity and enhancement of collagen IV synthesis were reserved incompletely by 606A. But complete reservation of MMP-2 activity and collagen IV synthesis was observed by using imidaprilat in cultured media in the experiments.