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 ...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.展开更多
目的:通过检测AA大鼠模型血清中基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-13(MMP-13)的表达水平,探讨MMP-3和MMP-13在RA发病中的作用机制。方法:选用SD大鼠32只,雌雄各半,随机分为4组,3个剂量组采用左足踝关节皮下分别注入不同浓度弗...目的:通过检测AA大鼠模型血清中基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-13(MMP-13)的表达水平,探讨MMP-3和MMP-13在RA发病中的作用机制。方法:选用SD大鼠32只,雌雄各半,随机分为4组,3个剂量组采用左足踝关节皮下分别注入不同浓度弗氏佐剂(CFA),空白对照组注射0. 15 m L生理盐水。观察各组大鼠足踝关节肿胀情况,确定大鼠足踝肿胀至最大程度所需时间(高峰时间)。另取SD大鼠50只,随机分为对照组和4个剂量组。高峰时间计算大鼠关节肿胀率,并检测血清中MMP-3和MMP-13的含量。结果:造模第8天,关节肿胀达到高峰。实验组间血清中MMP-3和MMP-13的含量与对照组相比,差异均有统计学意义(P <0. 05),且注射0. 15 m L和0. 20 m L CFA血清中MMP-3和MMP-13的含量能够分别达到最高浓度。结论:佐剂性关节炎大鼠血清中MMP-3和MMP-13这两种蛋白酶表达水平均明显升高,可能参与疾病的病理机制过程。展开更多
We designed and synthsized a series of novel 6-oxo-l,6-dihydropyrimidine-2,5-dicarboxamide derivatives and evaluated their inhibition effects on MMP 3, MMP 12 and MMP 13. The pharmacological results show that they hav...We designed and synthsized a series of novel 6-oxo-l,6-dihydropyrimidine-2,5-dicarboxamide derivatives and evaluated their inhibition effects on MMP 3, MMP 12 and MMP 13. The pharmacological results show that they have potent and highly selective activity of inhibiting MMP 13.展开更多
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),Chinathe National Institutes of Health(Nos.HL60942 and HL123568),USA
文摘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.
文摘目的:通过检测AA大鼠模型血清中基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-13(MMP-13)的表达水平,探讨MMP-3和MMP-13在RA发病中的作用机制。方法:选用SD大鼠32只,雌雄各半,随机分为4组,3个剂量组采用左足踝关节皮下分别注入不同浓度弗氏佐剂(CFA),空白对照组注射0. 15 m L生理盐水。观察各组大鼠足踝关节肿胀情况,确定大鼠足踝肿胀至最大程度所需时间(高峰时间)。另取SD大鼠50只,随机分为对照组和4个剂量组。高峰时间计算大鼠关节肿胀率,并检测血清中MMP-3和MMP-13的含量。结果:造模第8天,关节肿胀达到高峰。实验组间血清中MMP-3和MMP-13的含量与对照组相比,差异均有统计学意义(P <0. 05),且注射0. 15 m L和0. 20 m L CFA血清中MMP-3和MMP-13的含量能够分别达到最高浓度。结论:佐剂性关节炎大鼠血清中MMP-3和MMP-13这两种蛋白酶表达水平均明显升高,可能参与疾病的病理机制过程。
文摘We designed and synthsized a series of novel 6-oxo-l,6-dihydropyrimidine-2,5-dicarboxamide derivatives and evaluated their inhibition effects on MMP 3, MMP 12 and MMP 13. The pharmacological results show that they have potent and highly selective activity of inhibiting MMP 13.
