Intensity of Myocardial Expression of Inducible Nitric Oxide Synthase Influences the Clinical Course of Human Immunodeficiency Virus-Associated Cardiomyopathy

Abstract

Cytokine activation seems to play a significant pathogenetic role in both HIV-DCM and IDCM. In HIV-DCM patients, the state of immunodeficiency may favor the selection of viral variants of increased pathogenicity, influencing the clinical course of cardiomyopathy by enhancement of the inflammatory process.

Cardiovascular complications in the acquired immunodeficiency syndrome

“…Myocardial dendritic cells may play a role in the interaction between HIV-1 and the cardiac myo cyte and in the activation of cytotoxic cytokines 17 . Dendritic cells can initiate the primary immunologic response and present the antigen to T-lymphocytes.…”

“…TNF-alpha produces a negative ino tropic effect by altering intracellular calcium ho meostasis, possibly by inducing nitric oxide (NO) synthesis, which also reduces myocyte contractil ity. Kan et al demonstrated that HIV gp120 enhances NO production by cardiac myocytes through p38 MAP kinase-mediated NK-kB activation 19 .Myocarditis and dilated cardiomyopathy are associated with markedly elevated cytokine pro duction, but the elevations may be highly local ized within the myocardium, making peripheral cytokine levels uninformative 20 . When myocar dial biopsies from patients with HIV-associated cardiomyopathy are compared to samples from patients with idiopathic dilated cardiomyopathy, the former stain more intensely for both TNFalpha and inducible nitric oxide synthase (iNOS).…”

“…When myocar dial biopsies from patients with HIV-associated cardiomyopathy are compared to samples from patients with idiopathic dilated cardiomyopathy, the former stain more intensely for both TNFalpha and inducible nitric oxide synthase (iNOS). Stain ing is particularly intense in samples from patients with a myocardial viral infection and correlates with CD4 count, independent of antiretroviral treatment 20 . Staining is also more intense in samples from patients with HIV-associated car diomyopathy coinfected with coxsackievirus B3, cytomegalovirus, EpsteinBarr virus or adenovi rus 20 .…”

“…Stain ing is particularly intense in samples from patients with a myocardial viral infection and correlates with CD4 count, independent of antiretroviral treatment 20 . Staining is also more intense in samples from patients with HIV-associated car diomyopathy coinfected with coxsackievirus B3, cytomegalovirus, EpsteinBarr virus or adenovi rus 20 . Moreover, staining for iNOS is more in tense in samples from patients coinfected with HIV-1 and coxsackievirus B3 or cytomegalovirus than in samples from patients with idiopathic di lated cardiomyopathy and myocardial infection with coxackievirus B3 or who had adenovirus in fection alone 20 .…”

“…Staining is also more intense in samples from patients with HIV-associated car diomyopathy coinfected with coxsackievirus B3, cytomegalovirus, EpsteinBarr virus or adenovi rus 20 . Moreover, staining for iNOS is more in tense in samples from patients coinfected with HIV-1 and coxsackievirus B3 or cytomegalovirus than in samples from patients with idiopathic di lated cardiomyopathy and myocardial infection with coxackievirus B3 or who had adenovirus in fection alone 20 . In patients with HIV-associated dilated cardiomyopathy and more intense iNOS staining, the survival rate was significantly lower: those whose samples stained more than 1 optical density unit had a hazard ratio of mortality of 2.57 20 .…”