Clinical course of cardiomyopathy in HIV-infected patients with or without encephalopathy related to the myocardial expression of tumour necrosis factor-alpha and nitric oxide synthase (Retraction of vol 14, pg 827, 2000)
ABSTRACT To define whether the development of encephalopathy influences the clinical course of HIV-associated cardiomyopathy (HIV-DCM) in relation to the myocardial expression of tumour necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS).
University hospitals and AIDS centres.
115 HIV-infected patients with echocardiographic diagnosis of HIV-associated cardiomyopathy (34 with encephalopathy and 81 without encephalopathy) were followed for a mean of 24 +/- 3.2 months. All patients underwent endomyocardial biopsy for determination of myocardial immunostaining intensity of TNF-alpha and iNOS. Cerebrospinal fluid (CSF) from patients with encephalopathy was examined for the presence of viruses. Patients underwent clinical examination every 3 months and echocardiographic examination every 6 months. The intensity of TNF-alpha and iNOS immunostaining was also evaluated on postmortem cerebral tissue of patients who died of congestive heart failure (CHF).
A greater impairment of echocardiographic parameters was observed in patients with HIV-associated cardiomyopathy after development of encephalopathy. These parameters tended to worsen progressively during the follow-up period and were inversely correlated with HIV-1 viral load, CD4 cell count, mini mental status score and the intensity of myocardial and cerebral TNF-alpha and iNOS staining. CSF specimens were available in 29 patients with encephalopathy. HIV-1 sequences were detected in CSF of all these patients with cytomegalovirus sequences in two. The mortality rate for CHF was greater among patients with encephalopathy (73% versus 12%).
The development of encephalopathy has an adverse effect on the clinical course of HIV-associated cardiomyopathy. In the relationship between cardiomyopathy and encephalopathy, the activation of iNOS by TNF-alpha may have a significant pathogenetic role in HIV disease.
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ABSTRACT: The HIV-1 accessory protein Tat has been found to exert profound effects on vascular cell behavior. Recently, Tat has been found to activate the c-Jun amino-terminal kinase (JNK1, SAPK) MAP kinase in lymphoid cells. We found that purified Tat rapidly activated JNK1 in human umbilical vein endothelial cells and ECV-304 cells, and coculture of ECV-304 cells with Tat-transfected HeLa cells resulted in persistent activation of JNK1. In addition, lower doses of Tat potentiated TNFalpha-induced JNK1 activation, although higher doses paradoxically diminished JNK1 activation by TNFalpha. Treatment of ECV-304 cells with Tat acutely increased intracellular oxidant levels, and Tat-induced oxidant activity was decreased by two structurally distinct NADPH oxidase inhibitors, diphenylene iodonium and apocynin. Both oxidase inhibitors and the thiol antioxidant N-acetyl cysteine decreased Tat-induced JNK1 activation in parallel with reduction in oxidant levels. Activation of JNK1 by Tat was also inhibited by cytochalasin B, suggesting that Tat signaling was dependent upon intact cytoskeletal function. Indeed, JNK1 activation by Tat was associated with actin microfilament rearrangement. We conclude that HIV Tat may cause acute and persistent activation of the JNK MAP kinase through activation of a specific oxidase.Virology 08/2001; 286(1):62-71. DOI:10.1006/viro.2001.0998 · 3.28 Impact Factor
- Journal of the Royal Society of Medicine 09/2001; 94(8):384-90. DOI:10.1161/01.CIR.0000031704.78200.59 · 2.02 Impact Factor
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ABSTRACT: Reviews and studies published before the introduction of highly active antiretroviral therapy (HAART) have tracked the incidence and course of HIV infection in relation to cardiac illness in both children and adults. The introduction of HAART regimens has significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected people expected. However, early data raised concerns about HAART being associated with an increase in both peripheral and coronary arterial diseases. In this review we discuss HIV-associated cardiovascular complications focusing on pathogenetic mechanisms that could have a role in diagnosis, management, and therapy of these complications in the HAART era.The Lancet Infectious Diseases 10/2001; 1(2):115-24. DOI:10.1016/S1473-3099(01)00067-6 · 19.45 Impact Factor