Interleukin-18, matrix metalloproteinase-22 and -29 are independent risk factors of human coronary heart disease

BackgroundCoronary 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 resultsImmunoblot 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).ConclusionsOur 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.摘要目 的探讨冠心病患者血浆白细胞介素18(IL18)水平是否与基质金属蛋白酶-22 和-29(MMP-22 和MMP-29)的表达水平相关, 以及此类患者血浆中MMP-22 及MMP-29 水平是否升高。创新点首次证实在动脉粥样硬化过程中炎症反应可能促进MMP-22 及MMP-29 的表达, IL18 是冠心病患者中调控MMP 表达的炎症因子之一。方 法通过免疫印迹分析检测IL18 对人体动脉平滑肌细胞MMP-22 的表达; 通过Mann Whitney 检验对来自于194 例冠心病患者和68 例对照组的前瞻性研究进行分析; 通过logistic 回归分析冠心病的独立风险因素; 通过Pearson 相关性分析IL18 和MMP-22 的表达水平与冠状动脉Gensini 积分的相关性; 通过多变量Pearson 相关性分析血浆MMP-22 水平与超敏C 反应蛋白(hs-CRP)及甘油三酯水平的相关性; 通过Spearman 相关性分析血浆IL18 水平与MMP-22 和MMP-29 的相关性。结 论冠心病患者血浆IL18 水平升高可能导致此类患者血浆MMP-22和MMP-29水平升高。IL18、MMP-22和MMP-29 可能是冠心病的生物标记物和独立风险因素。

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