Abstract 3213: C-type Natriuretic Peptide Ameliorates the Progression of Experimental Autoimmune Myocarditis
Background: Recently, we have shown that the cardiac C-type natriuretic peptide (CNP) gene expression was increased in the infarct region and the administration of CNP attenuated the development of cardiac remodeling after myocardial infarction in rats. Autoimmune myocarditis is a T-cell-mediated disorder and the involvement of Th1/Th2 unbalance has been demonstrated. However, the effects of CNP on autoimmune myocarditis are not well-known. In the present study, we assessed the hypothesis that CNP might attenuate the progressive experimental autoimmune myocarditis (EAM) in rats by modulating the activation of helper T cells, as well as suppressing the expression of inflammatory cytokines.
Methods and Results: Male Lewis rats were immunized on days 0 and 7 with porcine cardiac myosin and EAM was induced. Rats were treated for 2 weeks with continuous CNP infusion at 0.1μg/kg/min (n=24) or vehicle (n=24). On day 21 after first immunization, the severity of myocarditis was evaluated by echocardiography, hemodynamics, pathology, and gene expressions in myocardium. Endogenous CNP gene expression increased in the myocardium in rats with EAM compared with sham rats. CNP improved the deteriorated left ventricular (LV) fractional shortening and LV enlargement. In a hemodynamic study, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt max/min in CNP-treated rats compared to vehicle-treated rats. CNP markedly attenuated an increase in morphometrical collagen volume fraction in LV with EAM. Interestingly, the treatment of CNP decreased the mRNA expression of interferon-γ and interleukin-2 (type 1 helper T cell cytokines) and increased the mRNA expression of interleukin-4 and interleukin-10 (type 2 helper T cell cytokines) in the heart of rats with myocarditis. CNP also decreased the mRNA expression of TNF -α and monocyte chemoattractant protein-1.
Conclusion: Administration of CNP improved LV dysfunction in rats with myocarditis probably via the modulation of helper T cell activation, suggesting the potential usefulness of CNP as a novel cardioprotective agent for autoimmune myocarditis.