| [Objective] To investigate the relationship between acute infections with microorganisms and acute coronary syndromes (ACS) onsets in patients with coronary heart disease (CHD), evaluate the clinical significance of high sensitivity C-reactive protein (hs-CRP) assays in these patients, and study the effects of CRP on expression of matrix metalloproteinase^2 (MMP-2) in HUVEC and U937 cells and the influence of CRP on matrix remodeling in atherogenesis and plaque rapture.[Methods] 1. Between October 2001 and April 2002, total 1847 patients with stable angina (SA), unstable angina (UA) or acute myocardial infarction (AMI) were investigated in 16 hospitals in Shanghai, China. In the investigation, case control study was used. All patients were divided into SA and acute coronary syndromes (ACS) group, and the different infection rates before the onsets of coronary events between these two groups were observed. Meanwhile, CRP levels of patients were assayed. 2. The serum hs-CRP levels in 157 patients with ACS, 56 patients with SA, 80 controls were measured at admission and at hospital discharge. All patients were selected in our hospital. According to Braunwald classification, the patients with UA were divided into Braunwald Gradeand on which hs-CRP were compared. All cardiovascular events (angina pectoris, myocardial infarction, death) were carefully observed and recorded in 6 months after hospital discharge. 3. HUVEC and U937 cells were cultured in vitro and intervened by different concentrations of recombination human CRP and provastatin [a: control (no CRP and provastatin); b: CRP 5ug/ml; c: CRP 20ug/ml; d: CRP 100ug/ml; e: CRP 20ug/ml+provastatin 10-3M. The MMP-2 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT- PCR) and MMP-2 protein was measured by western blotting.[Results] 1. The infection rate of ACS group(1143 cases) is42. 43%, which is higher than that of SA group(644 cases, 27.33%), P<0.01. Most, of infection diseases were upper respiratory infection and pneumonia, and these infection diseases happened within 2 weeks before angina or AMI in 78. 76% patients with ACS and in 43. 75% patients with SA. There were 61. 06% patients in ACS group whose CRP levels were higher than normal, 42.35% in SA group, p<0. 05. 2. Hs-CRP levels of patients with UA and AMI at admission (7. 96 2.31mg/L and 25.67 4. 78mg/L) were higher than controls(1.14 1.02mg/L) and SA group (3. 23 2. 36mg/L), P<0.01. Hs-CRP levels of Braunwald Grade I, II and III at adimission were 3.84 2.15mg/L, 8.23 2.13mg/L, 11.18 2.39mg/L respectively, which decreased to 3. 66 2. 61mg/L, 7. 33 + 2. 07mg/L, 9. 24 + 2. 14mg/L at discharge respectively. In patients with ACS whose hs-CRP levels increased atdischarge, the frequency of cardiovascular events in 6 months was higher than others, 37. 3% and 16. 0%, respectively, P<0.01. 3. In comparison with the control, the expression of mRNA and protein of MMP-2 was significantly increased in b, c, and d group(P<0.05), and this up-regulation of the expression of MMP-2 could be inhibited by provastatin in e group.[Conclusions] 1. The onsets of ACS may be relative to acute infection diseases. As a inflammation marker, CRP has predictive evaluation value to the onsets of ACS in patients with CHD. 2. The hs-CRP levels of patients with ACS were significantly higher than controls. Patients whose hs-CRP levels increased at discharge may be easier to have cardiovascular events than others. 3. CRP can enhance the expression of MMP-2 in U937 cells and may cause advanced inflammation in AS plaques. It may provide an explanation for the phenomenon that patients who have high concentration of CRP are prone to have atherosclerotic lesions and plaque rapture.
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