Retrovirally induced dilated cardiomyopathy in murine acquired immunodeficiency syndrome

Abstract

Acquired immunodeficiency syndrome (AIDS) has been associated with several cardiovascular abnormalities including dilated cardiomyopathy (DCM). DCM is characterized by dilation of the left ventricle and abnormal systolic and diastolic left ventricular function and is often associated with myocarditis and alterations in the extracellular matrix. The prevalence and severity of AIDS-associated DCM necessitates a better understanding of its disease process. To study AIDS DCM, the LP-BM5 murine AIDS (MAIDS) model, which offers many similarities to AIDS and several advantages as a model, was used. The cardiac function of MAIDS mice was compared to control mice using a conductance catheter system and left ventricular dimensions and compliance were significantly altered indicating a dilated cardiomyopathy. Competitive polymerase chain reaction was used to quantify the LP-BM5 retrovirus in splenic and cardiac tissue from MAIDS mice and illustrated active viral replication in spleen as well as heart tissue during the disease process. Immunohistochemistry and Northern blot analysis were used to determine the role of inflammation in this process: No staining was observed for immune cell infiltrates or the inflammatory mediators tumor necrosis factor-alpha and inducible nitric oxide synthase. The content of cardiac collagen, the major determinant of ventricular architecture, was significantly decreased in MAIDS mice compared to controls and LP-BM5 was shown to infect cardiac fibroblasts in vitro. Pharmacological treatment with zidovudine and/or indinavir prevented cardiac dysfunction through decreases in viral load without functional cardiotoxicity.