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Diffuse-regressive alterations and apoptosis of myocytes: possible causes of myocardial dysfunction in HIV-related cardiomyopathy.

Abstract：

OBJECTIVE: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. DESIGN:Retrospective study of 94 complete necropsies. METHOD:Macroscopic, histopathologic (histochemical, immunohistochemical and in situ hybridization techniques) and ultra structural myocardial evaluation (23 cases). RESULTS: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. CONCLUSIONS: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.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Pozzan G,Pagliari C,Tuon FF,Takakura CF,Kauffman MR,Duarte MI

doi

10.1016/j.ijcard.2007.10.057

subject

Has Abstract

pub_date

2009-02-06 00:00:00

pages

90-5

issue

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(07)01979-1

journal_volume

132

pub_type

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Diffuse-regressive alterations and apoptosis of myocytes: possible causes of myocardial dysfunction in HIV-related cardiomyopathy.