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

• Published in: International journal of cardiology Vol. 132; no. 1; pp. 90 - 95
• Main Authors: Pozzan, Geanete, Pagliari, Carla, Tuon, Felipe Francisco, Takakura, Cleusa Fumika, Kauffman, Monica R, Duarte, Maria Irma Seixas
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 06.02.2009; Elsevier
• Subjects: Adolescent; Adult; Aged; AIDS; Apoptosis; Biological and medical sciences; Cardiology. Vascular system; Cardiomyopathy, Dilated - etiology; Cardiomyopathy, Dilated - pathology; Cardiomyopathy, Dilated - physiopathology; Cardiovascular; Child; Child, Preschool; Dilated cardiomyopathy; Disease Progression; Female; Heart; HIV infection; HIV Infections - complications; HIV Infections - pathology; HIV Infections - physiopathology; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunohistochemistry; Immunopathology; Infant; Infectious diseases; Male; Medical sciences; Middle Aged; Myocarditis; Myocarditis. Cardiomyopathies; Myocytes, Cardiac - cytology; Myocytes, Cardiac - pathology; Myocytes, Cardiac - ultrastructure; Retrospective Studies; Tumor Necrosis Factor-alpha - analysis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Young Adult; Heart; Myocarditis; AIDS; Dilated cardiomyopathy; HIV infection; Apoptosis; Diffuse; Immunopathology; Cardiac performance; Retroviridae; Alteration; Cardiovascular disease; Immune deficiency; Lentivirus; Myocardial disease; Myocyte; Infection; Virus; Congestive hypertrophic cardiomyopathy; Heart disease; Viral disease; Cause; Human immunodeficiency virus; Cardiology
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2007.10.057

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 α (TNF α) 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 α 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.