Mmp-9 In Kawasaki Disease Coronary Artery Injury

Kawasaki disease (KD) has now surpassed acute rheumatic fever as the most common cause of acquired heart disease in children. Coronary artery dilataltion or aneurysm formation are mainly complications of KD. Though the pathogenesis of KD is still not fully understood, studies have implicated the imbalance between synthesis and degradation of extracellular matrix of arteries in the pathogenesis of the arterial lesions in KD. This imbalance may result in vascular remodeing: thinning of the vascular media and marked destruction of the internal elastic laminas of the arterial wall, and marked transmural infiltration of inflammatory cells, which leads to coronary artery dilation or aneurysm formation and stenosis in future.Extracellular matrix is the mainly component of vascular wall, and matrix metalloproteinases(MMPs), a family of enzymes producted by a variety of cell types, has the ability to degrade most components of the ECM. MMPs may play an important role in maintaining the integrity and stabilizing in vascular wall structure in physiological conditions and they have been implicated as mediators in pathologic processions of ECM destruction and remodeling in atherosclerosis and abdominal aortic aneurysm formation. â…£ collagen and elastin are the main structure components of vascular wall. As the main enzyme for degradeing â…£ collagen and elastin, Matrix metalloproteinases 9(MMP-9) may play an important role in some diseases characterized by vascular remodeling and cause more and more attentions. The tissue inhibitors of metalloproteinase 1(TIMP-1) is an important inhibitor of MMP-9. The activity of proMMP-9 and MMP-9 is inhibited by the binding of TIMP-1 in a 1 : 1 molar ratio. There is accumulating evidence of complicated interactions among vascular cells, ie. endothelial cells, smooth muscle cells and monocytes/macrophages, in the regulation of vascular function and remodeling. All-trans retinoic acid (atRA) are the natural derivatives ofvitamin A. Recently, researches have shown atra can exert many biological effects in vascular remodeling and regulate the expression of MMPs.In order to understand the role of MMP-9 in the pathomechanisms of coronary artery lesions in KD, three- part study is carried out.Part â… : MMP-9 and TIMP-1 expressions in the peripheral blood of patients with Kawasaki disease and relation between it and coronary artery lesionsObjective: To investigate the potential role of MMP-9 and TIMP-1 in the pathogenesis of coronary artery lesions in patients with KD.Methods : 40 patients with KD, including 23 patients who had no coronary artery lesions(CALs) and 17 patients who had CALs, as well as age-matched febrile(n=10) and afebrile(n=10) controls patients were studied. Gelatin zymography was used to detect the MMP-9 enzyme activity. Serum protein levels of MMP-9 and TIMP-1 were measured by enzyme-linked immunosorbent assay(ELISA). Expression of MMP-9 mRNA and TIMP-1 mRNA in the leucocytes were studied using reverse transcription-polymerase chain reaction(RT-PCR).Results: (1) The activity and protein level of MMP-9 , TIMP-1 level and MMP-9/TIMP-1 ratio during the acute phase of two groups of KD were significantly higher than those in the febrile and afebrile controls(P<0.01) and decreased obviously from the subacute through the convalescent phases(compared among three phases: P<0.01). Moreover, the activity and protein level of MMP-9, MMP-9/TIMP-1 ratio in the acute phase of KD with CALs were significantly elevated, compared to those in KD without CALs(P<0.05). (2) There is a significantly positive correlation between the serum protein level of MMP-9 in the acute phase of KD and the circulating leucocyte counts(r=0.539,P<0.001). (3) The expression of MMP-9 mRNA and TIMP-1 mRNA in the leucocytes in theacute phase of KD were also significantly elevated, compared with the febrile and afebrile controls(P<0.01).Conclusions: Over Expression of MMP-9 in the acute phase of KD may be involved in the formation of coronary artery lesions and pathogenesis of KD. High levels of MMP-9 and ratio of MMP-9/TIMP...