GW25-e1134 Clinical significance of serum homocysteine detection in patients with coronary heart disease

Abstract

Objectives: The reduction of myocardial matrix metalloproteinases-2 (MMP-2) in early hypertension has been shown that may lead to collagen accumulation in extra cellar matrix (ECM) and myocardial fibrosis. CD147 is a natural inducer of MMP-2. We assume that the inhibition of CD147/MMP-2 pathway may contribute to this remodeling. So we intend to alter the level of CD147/MMP-2 in early hypertensive rats by injecting exogenous CD147 protein, and observe its effect on ventricular remodeling. Methods: 30 healthy eight weeks male spontaneously hypertensive rats (SHR) were divided into 3 groups: SHR group (n¼10): normal saline via tail vein injection (iv.) qd ; CD147 group (n¼10): CD147 600ng$kg -1 iv. qw; CD147+DOX group (n¼10): CD147 600ng$kg -1 iv. qw and DOX (doxycycline, broad-spectrum inhibitor of MMPs) 30 mg$kg -1 qd via gavage. 10 healthy eight weeks male Wistar-Kyoto rats (WKY) were treated as the control gourp (WKY group, n¼10). Left ventricular mass indexs [LVWI¼ LV mass (mg)/ weight (g)] were measured and calculated; Myocardial sections were observed by HE coloration, VG coloration; Collagen volume fractions (CVF) were obtained by image analysis; The proteins of MMP-2, TIMP-1 and CD147 in myocardial tissue were assessed by western blot after the rats were sacrificed in Day 56th. Results: The contents of CD147 protein in myocardium of SHR group were reduced significantly (P<0.05) and the contents of MMP-2 were also reduced slightly compare with those in WKY group (P>0.05); The abundance of CD147 and MMP-2 protein in CD147 group was increased obviously (P<0.05), however, that of MMP-2 protein was reduced in CD147+DOX group after DOX intervention (P<0.05); The levels of TIMP-1 in the myocardium of three SHR groups, particularly in the CD147 group, were significantly higher than WKY group (P<0.05); The ratios of myocardium MMP-2/TIMP-1 in SHRs were less than WKYs obviously (P<0.05), but they were improved after CD147 intervention. LVWIs of SHR group were higher than WKY group (P<0.05), but they were downregulated obviously in CD147 group and CD147+DOX group (P<0.05). The myocardial biopsy showed that there were cardiomyocyte hypertrophy, some myocardial fibre rupture, myocyte dissolution and fuzzy myocardial fibre boundaries in SHR group . The cardiac structure was improved significantly after CD147 intervention, but it was surpressed when DOX administrated simultaneously. VG coloration sections were seen more abundant collagen fibers and higher CVF in the myocardiums of SHR group than those in WKY group (P<0.05). The contents of collagen fiber and the CVFs were decreased significantly after CD147 intervention (P<0.05). While, they were increased again in CD147+DOX group (P<0.05). Conclusions: The inhibition of CD147/MMP-2 pathway, the reduction of MMP-2 protein expression and the imbalance of MMP-2/TIMP-1 may contribute to early ventricular remodeling in SHR. Appropriate myocardial CD147 protein upregulation may attenuate the process of early hypertensive ventricular remodeling. GW25-e1393Relationship between p...