Regulation of Inflammation and Myocardial Fibrosis in Experimental Autoimmune Myocarditis
Kenichi Watanabe, Vijayakumar Sukumaran, Punniyakoti T. Veeraveedu, Rajarajan A. Thandavarayan, Narasimman Gurusamy, Meilei Ma, Wawaimuli Arozal, Flori R. Sari, Arun Prasath Lakshmanan, Somasundaram Arumugam, Vivian Soetikno, Varatharajan Rajavel and Kenji Suzuki
Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University ofPharmacy and Applied Life Sciences, 265-1 Higashizima, Niigata City, 956-8603, Japan.
Autoimmune responses and inflammation are involved in the pathogenesis of many cardiovascular diseases. There is compelling evidence that inflammatory mechanisms may contribute to progressive heart failure. Thus, myocardial infiltration of lymphocytes and mononuclear cells, increased expression of pro-inflammatory chemokines and cytokines and circulating autoantibodies are frequently observed in myocarditis and dilated cardiomyopathy (DCM). Experimental autoimmune myocarditis (EAM) in rodents may be elicited by immunization of cardiac myosin and EAM in rats mimics human fulminant myocarditis in the acute phase and human DCM in the chronic phase. Our animal model, EAM was demonstrated to progress into the clinicopathological state similar to DCM in the chronic phase, and was found to be characterized by the enlargement of the heart, dilatation of ventricles, diffuse and extensive myocardial fibrosis, besides being a cellular immunity and inflammation mediated disease. Severity of myocarditis was characterized by increased inflammation, cardiac fibrosis and decreased myocardial performance in rats with DCM. Pharmacological interventions such as angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) significantly attenuated the myosin-induced inflammation and cardiac fibrosis and thereby improving myocardial function in rats with DCM. A growing body of evidence shows that ACEI and ARBs contribute to the pharmaceutical management of patients with heart failure mediated by immune and inflammatory response. The purpose of this review is to emphasize the role of inflammation and myocardial fibrosis in rats with DCM after EAM and study the effects of pharmacological interventions such as ACEI, ARBs in the treatment of heart failure through the suppression of inflammatory cytokines and fibrosis.
Keywords: Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, myocardial fibrosis, dilated, cardiomyopathy, experimental autoimmune myocarditis, inflammation, Autoimmune Myocarditis, cardiovascular diseases, myocardial infiltration, Myocardial Injury
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