摘要
Background： Coronary heart disease （CHD） is characterized by arterial wall inflammation and matrixdegradation. Matrix metalloproteinase （MMP）-22 and -29 and pro-inflammatory cytokine interleukin-18 （IL18） arepresent in human hearts. IL18 may regulate MMP-22 and -29 expression, which may correlate with CHD progression.Methods and results： Immunoblot analysis showed that ILl8 induced MMP-22 expression in human aortic smoothmuscle cells. The Mann Whitney test from a prospective study of 194 CHD patients and 68 non-CHD controlsdemonstrated higher plasma levels of IL18, MMP-22 and-29 in CHD patients than in the controls. A logistic regressiontest suggested that plasma IL18 （odds ratio （OR）=1.131, P=0.007）, MMP-22 （OR=1.213, P=0.040）, and MMP-29（OR=1.198, P=0.033） were independent risk factors of CHD. Pearson＇s correlation test showed that IL18 （coefficient（r）=0.214, P=0.045; r=0.246, P=0.031） and MMP-22 （t=0.273, P=0.006; r=0.286, P=0.012） were associated with theGensini score before and after adjusting for potential confounding factors. The multivariate Pearson＇s correlation testshowed that plasma MMP-22 levels correlated positively with high-sensitive-C-reactive protein （hs-CRP） （r=0.167,P=0.023）, and MMP-29 levels correlated negatively with triglyceride （t=-0.169, ,P=-0.018）. Spearman＇s correlation testindicated that plasma IL18 levels associated positively with plasma MMP-22 （t=0.845, P〈0.001） and MMP-29 （r=0.548P〈0.001）. Conclusions： Our observations suggest that IL18, MMP-22 and -29 serve as biomarkers and independentrisk factors of CHD. Increased systemic IL18 in CHD patients may contribute to elevated plasma MMP-22 and -29levels in these patients.
Background: Coronary heart disease(CHD) is characterized by arterial wall inflammation and matrix degradation. Matrix metalloproteinase(MMP)-22 and-29 and pro-inflammatory cytokine interleukin-18(IL18) are present in human hearts. IL18 may regulate MMP-22 and-29 expression, which may correlate with CHD progression. Methods and results: Immunoblot analysis showed that IL18 induced MMP-22 expression in human aortic smooth muscle cells. The Mann Whitney test from a prospective study of 194 CHD patients and 68 non-CHD controls demonstrated higher plasma levels of IL18, MMP-22 and-29 in CHD patients than in the controls. A logistic regression test suggested that plasma IL18(odds ratio(OR)=1.131, P=0.007), MMP-22(OR=1.213, P=0.040), and MMP-29(OR=1.198, P=0.033) were independent risk factors of CHD. Pearson's correlation test showed that IL18(coefficient(r)=0.214, P=0.045; r=0.246, P=0.031) and MMP-22(r=0.273, P=0.006; r=0.286, P=0.012) were associated with the Gensini score before and after adjusting for potential confounding factors. The multivariate Pearson's correlation test showed that plasma MMP-22 levels correlated positively with high-sensitive-C-reactive protein(hs-CRP)(r=0.167, P=0.023), and MMP-29 levels correlated negatively with triglyceride(r=-0.169, P=0.018). Spearman's correlation test indicated that plasma IL18 levels associated positively with plasma MMP-22(r=0.845, P<0.001) and MMP-29(r=0.548, P<0.001). Conclusions: Our observations suggest that IL18, MMP-22 and-29 serve as biomarkers and independent risk factors of CHD. Increased systemic IL18 in CHD patients may contribute to elevated plasma MMP-22 and-29 levels in these patients.
基金
supported by the University of Science and Technology Innovation Team of Henan(No.14IRTSTHN018)
the Science and Technology Talents Team Construction Program of Zhengzhou City Science and Technology Talents(No.131PLJRC670),China
the National Institutes of Health(Nos.HL60942 and HL123568),USA
