AIDS cardiomyopathy: physiological, molecular, and biochemical studies in the transgenic mouse.

Cardiomyopathy in AIDS (AIDS CM) is an important and prevalent clinical problem. Mechanisms of AIDS CM are not completely understood. Among the potential etiologies of AIDS CM are HIV-1, various opportunistic infections, inflammatory reactions, cytokine effects, and cardiotoxicity of prescribed or illicit drugs. The transgenic mouse (TG) offers a unique in vivo way to elucidate mechanisms of AIDS CM. Structural and functional effects of HIV-1 and specific HIV-1 gene products on heart tissue can be addressed by TGs. Selective effects of HIV-1 and antiretroviral therapy may be defined in controlled studies. We utilized AIDS TGs with generalized expression of HIV-1 gene products in CM models. We treated those TGs with individual and combined antiretroviral therapeutics (HAART) to compare cardiovascular effects of AIDS per se and its therapy. We next developed cardiac-specific TGs in which selected HIV-1 genes are driven by alpha-myosin heavy chain promoter to target the selected HIV-1 gene to the cardiac myocyte to define effects of specific HIV-1 gene products on the cardiac myocyte. Each transgenic approach is a model system that affords a distinct opportunity to explore the pathogenesis and pathophysiology of AIDS CM.