Pathogenetic Hypotheses

Three possibilities can explain HIV-associ­ated vascular alterations: (1) direct cellular infection by HIV (macrophages, smooth muscle cells, endothelial cells), (2) blood coagulation alterations, and (3) cellular infection by opportunistic elements [13].

1. Direct cellular infection by HIV-1. This phenomenon is demonstrated for macrophages, which is the first cellular target of the virus along with CD4 lym­phocytes. It has not been demonstrated in vitro for endothelial cells, but some modifications are perhaps due to this alteration: von Willebrand’s factor VIII, soluble thrombomodulin, E-selectin, and CD4 molecule increase [14]. These modi­fications involve endothelium proper- ties-antigen presentation: IL-1; TNF-α secretion; and IL-2 production by T cells, which secondarily involve basal mem­brane degradation via Tat protein [15, 16]. Morphogenetic modifications of intimal intercellular matrix facilitate the penetration of lymphocytes and macrophages that are the target cells for HIV infection and replication. Infected macrophages would initiate medial smooth muscle activation and prolifera­tion [17]. Endothelial cells seem to be heterogeneous, with discontinuous cells of sinusoid capillary cells displaying a different behavior [18]. HIV-1 sequences have been detected by in situ hybridiza­tion in the coronary vessels of an HIV- infected patient who died from acute myocardial infarction [19]. Potential mechanisms through which HIV-1 may damage coronary arteries include activa­tion of cytokines and cell-adhesion mole­cules and alteration of major histocom­patibility complex class I molecules on the surface of smooth muscle cells [19].

2. Hypercoagulability has been demonstrat­ed in AIDS: von Willebrand’s factor and tissular plasminogen activator increase, while there is a decrease in beta-2 microglobulin, S protein-free plasmatic fraction (protein C cofactor), and second heparin-cofactor (thrombin inhibitor). Other possible thrombogenic factors can be demonstrated: antiphospholipid anti­bodies (70% of AIDS cases) and lipopro­tein LP(a) increase (common epitope for HIV and blood platelets), whereas hyper­triglyceridemia and apolipoprotein AII decrease [20, 21].

3. Opportunistic infections demonstrate vas­cular tropism [22]. Viral cytolysis and en­dothelial necrosis favor the parietal ad­hesion of macrophages, an early known atherosclerotic stage. Cytomegalovirus al­ters endothelial cells as well as smooth muscle medial cells leading to multiplica­tion, phenotype transformation with colla­gen and microelastic element synthesis and foam cells formation.

Experimental pathology studies in Maca- cus monkeys demonstrate a diffuse arteri- opathy present in 25% of the population after simian immunodeficiency virus (SIV) infection, without a proven responsibility for either SIV or opportunistic infection [23].