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Background— Experimental autoimmune myocarditis (EAM), a mouse model of post–infectious cardiomyopathy, reflects mechanisms of inflammatory cardiomyopathy in humans. EAM is characterized by an infiltration of inflammatory cells into the myocardium that can be followed by myocyte fibrosis, edema, and necrosis, leading to ventricular wall dysfunction and heart failure. Different data indicate that CD69 exerts an important immunoregulatory effect in vivo. However, the possible role of CD69 in autoimmune myocarditis has not been studied. Methods and Results— We have explored the role of the leukocyte regulatory molecule CD69 in the inflammation that leads to cardiac dysfunction after myocardial injury in EAM. We have found that after induction of EAM, the draining lymph nodes from CD69-deficient mice developed an exacerbated Th17 inflammatory response, resulting in increases in the numbers of infiltrating leukocytes in the myocardium. In the chronic phase of EAM, transthoracic echocardiography revealed a significantly reduced left ventricular fractional shortening and a decreased ejection fraction in CD69-deficient mice, indicative of an impaired cardiac contractility. This condition was accompanied by a greater extent of myocardial fibrosis, an elevated number of sinus pauses on ECG, and an enhanced ratio of heart weight to body weight in CD69 −/− mice. Moreover, both bone marrow transplantation and adoptive transfer of Th17 cells isolated from immunized CD69 −/− mice with EAM into naive wild-type recipients reproduced the severity of the disease, demonstrating that CD69 exerts its function within the lymphocyte compartment. Conclusion— Our findings indicate that CD69 negatively regulates heart-specific Th17 responses, cardiac inflammation, and heart failure progression in EAM.

This study evaluated the effects of N-acetyl-l-cysteine (NAC), a free radical scavenger, and Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide (NO) synthesis inhibitor, on the changes in renal function, intrarenal blood flow distribution (laser-Doppler flowmetry), and plasma peroxynitrite levels during the acute renal failure (ARF) produced by inferior vena cava occlusion (IVCO; 45 min) in anesthetized rats. Renal blood flow fell on reperfusion (whole kidney by −45.7%; cortex −58.7%, outer medulla −62.8%, and papilla −47.7%); glomerular filtration rate (GRF) also decreased (−68.6%), whereas fractional sodium excretion (FENa%) and peroxynitrite and NO[Formula: see text]/NO[Formula: see text] plasma levels increased (189.5, 46.5, and 390%, respectively) after ischemia. Pretreatment with l-NAME (10 μg · kg−1· min−1) aggravated the fall in renal blood flow seen during reperfusion (−60%). Pretreatment with NAC (150 mg/kg bolus + 715 μg · kg−1· min−1iv) partially prevented those changes in renal function (GFR only fell by −29.2%, and FENa%increased 119.4%) and laser-Doppler blood flow, especially in the outer medulla, where blood flow recovered to near control levels during reperfusion. These beneficial effects seen in rats given NAC seem to be dependent on the presence of NO, because they were abolished in rats pretreated with l-NAME. Also, the antioxidant effects of NAC prevented the increase in plasma peroxynitrite after ischemia. In conclusion, NAC ameliorates the renal failure and the outer medullary vasoconstriction induced by ICVO, effects that seem to be dependent on the presence of NO and the scavenging of peroxynitrite.