Experimental And Clinical Study On Relation Between MMP-2 And Unstable Angina

[Objective] Currently, diagnosis of unstable angina (UA) is mainly dependent on clinical symptoms and is deficient of index, which is sensitive and specific. It has been demonstrated that most of UA onset is related to coronary plaque disruption. However, high expression or increasing activity of matrix metalloproteinases (MMPs) can lead to coronary instability and disruption. It has been reported that serum MMPs level significantly rose in patients with acute coronary syndromes (ACSs). In this study, effects of ox-LDL on secretion of MMP-2 by human umbilical vein endothelial cells (HUVEC) were preliminarily investigated and MMP-2 was chosen to investigate its determinant value to UA.[Methods]() Experimental part: After being separated ,cultured and identified, HUVEC was stimulated by ox-LDL, then MMP-2 level in supernatant of cultured HUVEC was determined by Enzyme Linked Immuno Sorbent Assay(ELISA). On the addition of VitE, the MMP-2 secreted by cultured HUVEC ,which was stimulated by ox-LDL, was partially inhibited.(.27) Clinical part: Serum MMP-2 and C-reactive protein(CRP) were measured in 46 patients with UA, 25 patients with stable angina(SA) and 22 healthy persons by ELISA. Serum total cholesterol was also measured in SA and UA groups and acute coronary events were instantaneously observed in two weeks.[Results]() Experimental part: ox-LDL could increase MMP-2 level in supernatant of cultured HUVEC, which began to rise at 6h and reached peak value at 24h. With increase of ox-LDL concentration, MMP-2 level in supernatant of cultured HUVEC appeared increase tendency. However, anti-oxidant VitE inhibited secretion of MMP-2 by HUVEC, which was stimulated by ox-LDL.(21)Clinical part: The serum MMP-2 levels in UA group on admission were significantly higher than that in SA group and control group (P<0.01), and the serum MMP-2 level in SA group was also higher than that in control group (P <0.05). The serum MMP-2 in UA group was on high level in first week and was significantly lower than that on admission in 15th day (P<0.0 1). The serum CRP levels in UA group on admission were significantly higher than that in control group, SA group and SA group (P<0.01), however, there was no difference between the control group and SA group (P<0.05). The serum CRP level in SA group was higher on admission, lth-day and 3th-day, and markedly decreased later. The number of hypercholesterolemia in SA group was larger than that in SA group (24 vs 6 respectively, P<0.05), and the average serum total cholesterol level in UA group was also significantly higher than that in SA group (5.75?.7SmmolIl vs 5.20?.68mmol/l respectively, P<0.01). There was no statistically difference on serum MMP-2 level among several subgroup of UA group and there was statistically difference on serum CRP levels. The serum MMP-2 and CRP in patients with acute coronary events were on high level.[Conclusion](1)ox-LDL could increase secretion of MMP-2 by HUVEC, and antioxidant could partially inhibited secretion of MMP-2 by HUVEC, which was stimulated by ox-LDL.(2)The serum MMP-2 in UA group was higher than that in control group and SA group, and the level after the symptom was abated was significantly lower than that on admission. It is speculated that MMP-2 is related to the coronary plaque instability and disruption, and that it might be helpful in the diagnosis of UA.(3)High serum cholesterol is positive correlative to serum MMP-2 level,so lipid- lowering might inhibit expression or activity of MMP-2.(4)Serum MMP-2 and CRP level can be used to estimate the prognosis of UA patients.