Angiogenesis in fatal acute Kawasaki disease coronary artery and myocardium.
Angiogenesis has been shown to be dysregulated in coronary artery (CA) aneurysms in the chronic phase of Kawasaki disease (KD). Neovascularization may occur in inflammatory-related vascular diseases because many angiogenesis mediators are secreted by inflammatory cells. We hypothesized that inflammation of the acute KD CA aneurysm could lead to dysregulation of angiogenesis mediators and subsequent neovascularization. To investigate this hypothesis, acute fatal KD cardiac tissues were immunostained for angiogenic inducers and inhibitors. Microvessel density was determined and the degree of inflammation assessed. Marked inflammation and angiogenesis were found in acute KD CA aneurysms and myocardium, with the highest microvessel density seen in patients who died 2-3 weeks after onset of the disease. Expression of proangiogenic proteins was higher than expression of inhibitors in KD CA aneurysms and myocardium. Angiogenesis mediators were localized to inflammatory cells in the myointima, adventitia, and myocardium. We conclude that significant neovascularization occurs in acute KD CA aneurysms and myocardium much sooner after onset of the disease than has been previously reported, that multiple angiogenesis factors are involved, and that dysregulation of angiogenesis likely contributes to KD vasculopathy.
Freeman
A F
AF
Department of Pediatrics, Feinberg School of Medicine, Northwestern University, W140, Ward 12-204, 303 E. Chicago Avenue, Chicago, IL 60611, USA. Freemaal@mail.nih.gov
Crawford
S E
SE
Cornwall
M L
ML
Garcia
F L
FL
Shulman
S T
ST
Rowley
A H
AH
D000208:Acute Disease; D017542:Aneurysm, Ruptured / Q000401:mortality; D043168:Angiostatins / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003323:Coronary Aneurysm / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008833:Microcirculation; D009080:Mucocutaneous Lymph Node Syndrome / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D009205:Myocarditis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000401:mortality*; D020932:Nerve Growth Factor / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D019699:Thrombospondins; D042461:Vascular Endothelial Growth Factor A; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D043168:Angiostatins; D020932:Nerve Growth Factor