OBJECTIVE: Coronary artery aneurysms are the major complication of Kawasaki disease (KD). Matrix metalloproteinases (MMPs) regulate remodeling and degradation of the extracellular matrix. We hypothesized that MMP-9 expression is increased in acute KD aneurysms when compared with KD nonaneurysmal arteries and arteries from control children. METHODS AND RESULTS: MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were immunolocalized in coronary arteries from children with fatal acute KD and controls. In KD coronary aneurysms, MMP-2 expression was prominent in the thickened neointima and in endothelial cells of new capillaries in areas of angiogenesis. MMP-9 was absent in control coronary arteries but was expressed in coronary artery aneurysms, nonaneurysmal coronary and noncoronary arteries, and cardiac nerves in acute KD, without an increase in TIMP-1 expression. CONCLUSIONS: MMP-2 likely participates in remodeling of the arterial wall in acute KD, particularly in the processes of neointimal proliferation and angiogenesis. MMP-9 may play a role in the development of coronary aneurysms, but its expression is not confined to aneurysmal arteries. Systemic arterial expression of MMP-9 in acute KD, even in the absence of inflammatory changes in the vessel, suggests induction by a circulating factor, or possibly by an infectious agent with tropism for arterial tissue.
OBJECTIVE:Coronary artery aneurysms are the major complication of Kawasaki disease (KD). Matrix metalloproteinases (MMPs) regulate remodeling and degradation of the extracellular matrix. We hypothesized that MMP-9 expression is increased in acute KD aneurysms when compared with KD nonaneurysmal arteries and arteries from control children. METHODS AND RESULTS:MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 were immunolocalized in coronary arteries from children with fatal acute KD and controls. In KD coronary aneurysms, MMP-2 expression was prominent in the thickened neointima and in endothelial cells of new capillaries in areas of angiogenesis. MMP-9 was absent in control coronary arteries but was expressed in coronary artery aneurysms, nonaneurysmal coronary and noncoronary arteries, and cardiac nerves in acute KD, without an increase in TIMP-1 expression. CONCLUSIONS:MMP-2 likely participates in remodeling of the arterial wall in acute KD, particularly in the processes of neointimal proliferation and angiogenesis. MMP-9 may play a role in the development of coronary aneurysms, but its expression is not confined to aneurysmal arteries. Systemic arterial expression of MMP-9 in acute KD, even in the absence of inflammatory changes in the vessel, suggests induction by a circulating factor, or possibly by an infectious agent with tropism for arterial tissue.
Authors: Andras Bratincsak; Blair N Limm-Chan; Vivek R Nerurkar; Lauren L Ching; Venu D Reddy; Eunjung Lim; Ralph V Shohet; Marian E Melish Journal: Contemp Clin Trials Date: 2017-12-05 Impact factor: 2.226
Authors: Karl G Sylvester; Xuefeng B Ling; G Y Liu; Zachary J Kastenberg; Jun Ji; Zhongkai Hu; Sihua Peng; Ken Lau; Fizan Abdullah; Mary L Brandt; Richard A Ehrenkranz; Mary Catherine Harris; Timothy C Lee; Joyce Simpson; Corinna Bowers; R Lawrence Moss Journal: Gut Date: 2013-09-18 Impact factor: 23.059