The role of inflammatory mechanisms in the pathogenesis of ischemic heart disease. Basic and clinical studies.

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We have obtained many important findings regarding the role of inflammatory mechanisms in the pathogenesis of coronary arteriosclerosis and ischemic heart disease.(1) Chronic treatment with interleukin-1beta (IL-1beta) causes remodeling, neointimal formation, and vasospastic responses of the coronary artery in pigs in vivo.(2) The same changes of the coronary artery were also noted by the chronic treatment with other major inflammatory cytokines, such as IL-1alpha and tumor necrosis factor-alpha, with the alterations in myosin heavy chain isoforms toward de-differentiation.(3) The IL-1beta-induced changes of the coronary artery were mediated by platelet-derived growth factor and fibroblast growth factor-2 in vivo.(4) The IL-1beta-induced changes of the coronary artery were markedly inhibited by cotreatment with ST 638, a specific inhibitor of tyrosine kinases, indicating the important role of tyrosine kinase activation in the pathogenesis of coronary arteriosclerosis in vivo.(5) The intracellular pathway mediated by protein kinase C (PKC) was substantially involved in the pathogenesis of coronary spasm at the arteriosclerotic lesions in vivo.(6) During the course of acute myocardial infaction, the plasma levels of some cytokines temporarily increased, while those of other cytokines were increased for a longer period.