Cytokines in HIV-associated cardiomyopathy
ABSTRACT Among the multiple cardiac manifestations occurring in HIV-infected patients, cardiomyopathy is one of the most challenging. Its incidence has only slightly decreased since the introduction of highly active antiretroviral therapy (HAART). Also, its pathogenesis remains relatively unclear. Although several studies demonstrated the presence of HIV genome in the heart of patients, more recent developments found that viral infection plays an indirect role only, as well as they recognized the contribution of proinflammatory cytokines in the progression of the disease. Experimental studies on animals and cultured myocytes have established the signalling pathway triggered by proinflammatory cytokines in heart failure and cardiomyopathy. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and IL-6 promote expression of inducible nitric oxide synthase (iNOS) in cardiomyocytes through activation of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor kappaB (NFkappaB). TNF-alpha and high concentrations of NO also induce cardiomyocyte apoptosis by TNF type 1 receptor activation. This biological framework, which is also involved in progression of cardiomyopathy in humans, is more pronounced in HIV-infected patients, in whom proinflammatory cytokines TNF-alpha, IL-1 and IL-6 are increased, resulting in an enhanced expression of cardiac iNOS, especially in patients with a low CD4 T cell count. This may account for the worse outcome of heart failure in HIV-infected patients. However, there are only few data today to support future therapeutic implications of cytokines antagonism in treatment of HIV-infected patients with cardiomyopathy. Whether modulation of TNF production or selective inhibition of p38 MAPK pathway could be useful approaches remains uncertain.
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ABSTRACT: As the number of children infected with HIV rises so does the number of patients with cardiac complications. These complications are miscellenous with uncharacteristic symptoms. Children with congestive cardiomiopathy resulting from HIV infection may manifest symptoms and signs of cardiac failure but most frequently the clinical course mimics infection of the respiratory system. All HIV positive children with symptoms suggesting respiratory tract infection must be evaluated cardiologically. In this paper we present an HIV infected 2,5 year old boy with congestive cardiomiopathy.Pediatria polska 11/2007; 82(11):889-892. DOI:10.1016/S0031-3939(07)70323-2
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ABSTRACT: To determine the frequency of cardiac alterations in necropsies of AIDS patients in pre-HAART era and better understand the pathogenesis of HIV-related cardiomyopathy. Retrospective study of 94 complete necropsies. Macroscopic, histopathologic (histochemical, immunohistochemical and in situ hybridization techniques) and ultra structural myocardial evaluation (23 cases). Cardiac alterations were observed in 94.4%; 74% showed variable degrees of cardiac dilation not related to known cardiovascular diseases. Eighty-two percent (81.8%) of patients with biventricular dilation showed diffuse-regressive alterations (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules). Myocarditis was diagnosed in 27 cases (28.7%), 16 (59.3%) of known etiology. The ultra structural study has revealed cardiomyocytes alterations (mitochondriosis, loss of myofibrils, increase in the amount of perinuclear-lipofuscin pigment granules) associated to activation signals of capillary-endothelial cells (enhancement of pseudopodia and transcellular channels). Cardiomyocytes' apoptosis was demonstrated at structural level in 10 (43.5%) patients; tumor necrosis factor alpha (TNF alpha) was detected in 17/18 cases. This pioneer study described the association of histopathological and ultra structural findings (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules, mitochondriosis and loss of myofibrils) with different degrees of cardiac-chamber dilation probably representing a spectrum of alterations that would lead to myocardial dysfunction and development of HIV-related cardiomyopathy. Cardiomyocytes' apoptosis observed at ultra structural level and demonstration of TNF alpha associated to described alterations suggest that this cytokine plays an important role in both negative-inotropic effect and capacity to induce apoptosis through death receptor-controlled pathway.International journal of cardiology 02/2008; 132(1):90-5. DOI:10.1016/j.ijcard.2007.10.057 · 6.18 Impact Factor