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(American Journal of Pathology. 2006;168:727-735.)
© 2006 American Society for Investigative Pathology

Bacterial Lipopolysaccharide Enhances Cardiac Dysfunction but Not Retroviral Replication in Murine AIDS

Roles of Macrophage Infiltration and Toll-Like Receptor 4 Expression

Alysia A. Chaves^*, Reshma S. Baliga^*, Michael J. Mihm^*, Brandon L. Schanbacher^*, Anupam Basuray^*, Cynthia Liu^*, Angela C. Cook^*, Leona W. Ayers and John Anthony Bauer^*

From the Center for Cardiovascular Medicine,^* Columbus Children’s Research Institute; and the Division of Pharmacology, College of Pharmacy, and the Departments of Pathology and Pediatrics, College of Medicine, The Ohio State University, Columbus, Ohio

Cardiovascular disease is an important complication of human immunodeficiency virus/acquired immune deficiency syndrome (AIDS), but the mechanism(s) involved are poorly understood. Although co-infecting pathogens have been implicated as an important factor in AIDS progression, no studies have investigated these interactions in cardiac tissue. We recently demonstrated that the murine AIDS model (LPBM5 retroviral infection) mimics human immunodeficiency virus-related cardiac dysfunction and pathology. We tested the hypothesis that subseptic lipopolysaccharide exposure (LPS) would enhance LPBM5 progression and exacerbate cardiovascular dysfunction during murine AIDS development. LPS (5 mg/kg, Escherichia coli 0111:B4) was administered at 1, 6, and 8 weeks during LPBM5 infection, and cardiac performance was evaluated at 10 weeks using noninvasive echocardiography. LPS alone had no significant effects, whereas it amplified abnormalities in cardiac structure and function observed in murine AIDS. Cardiac dysfunction was associated with selective increases in nonfocal infiltration of CD68⁺ cells and correlated with the extent of cardiac dysfunction. Retroviral progression and cardiac retroviral content remained unaltered, but cardiac toll-like receptor 4 was increased in retrovirus + LPS. We provide first-time evidence of multipathogen enhancements to retrovirus-related cardiac complications and implicate innate immune responses, not co-pathogen-induced retroviral replication, as the primary mechanism in this setting.