ABSTRACT
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.
Subject(s)
Coronary Aneurysm/mortality , Coronary Vessels/pathology , Mucocutaneous Lymph Node Syndrome/mortality , Mucocutaneous Lymph Node Syndrome/pathology , Myocardium/pathology , Neovascularization, Pathologic/mortality , Acute Disease , Aneurysm, Ruptured/mortality , Angiostatins/metabolism , Case-Control Studies , Child , Coronary Aneurysm/metabolism , Coronary Aneurysm/pathology , Coronary Vessels/metabolism , Female , Fibroblast Growth Factor 2/metabolism , Humans , Immunohistochemistry , Infant , Infant, Newborn , Male , Mast Cells/metabolism , Microcirculation , Mucocutaneous Lymph Node Syndrome/metabolism , Myocarditis/metabolism , Myocarditis/mortality , Myocarditis/pathology , Myocardium/metabolism , Neovascularization, Pathologic/metabolism , Nerve Growth Factor/metabolism , Platelet-Derived Growth Factor/metabolism , Thrombospondins/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The pathogenesis of coronary arterial inflammation in acute Kawasaki disease (KD) is unclear. To test the hypothesis that the KD vascular lesion is an activated T lymphocyte-dependent process, immunohistochemical studies were done on coronary artery aneurysms from 8 fatal acute KD cases by using antibodies to CD45RO (activated or memory T lymphocyte), CD8 (cytotoxic T lymphocyte), CD4 (helper T lymphocyte), HAM56 (macrophage), and CD20 (B lymphocyte). Acute KD coronary arteritis was characterized by transmural infiltration of CD45RO T lymphocytes with CD8 T lymphocytes predominating over CD4 T lymphocytes. Macrophages were present primarily in the adventitial layer; B lymphocytes were notably absent. These data lend support to the hypotheses that KD results from infection with an intracellular pathogen, such as a virus, whose antigens are presented by major histocompatibility complex class I molecules, and that CD8 T lymphocytes and macrophages are important in the pathogenesis of KD coronary aneurysms.
