Abstract
BackgroundHIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs).ResultsMSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPARγ activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context.ConclusionsThe HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients.
Highlights
HIV infection elicits the onset of a progressive immunodeficiency and damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone
The cells were stained for 20 minutes at room temperature using the following monoclonal antibodies: fluorescein isothiocyanate (FITC) anti-CD29, phycoerythrin (PE)-anti-CD34, FITC-anti-CD44, FITC-antiCD45, FITC-anti-CD73, PE-anti-CD90, PE-anti-CD105, PE-anti-CD146, PE-anti-CD166 and FITC-anti-KDR,. vWF expression was revealed after permeabilization with the Intraprep Kit (Beckman-Coulter), incubated with vWFmAb (1/20 in phosphate-buffered saline (PBS); DakoCytomation, Glostrup, Denmark) for 1 hour at room temperature and subsequently incubated with secondary anti-mouse IgG FITC (1/40 in PBS; DakoCytomation) for 30 minutes at room temperature
In the series of experiments, we studied whether HIV-1 strains and/or gp120 elicited apoptosis in mesenchymal stem cells (MSCs) differentiated towards adipogenic and endothelial cell lineages
Summary
HIV infection elicits the onset of a progressive immunodeficiency and damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. Carotid artery thickening was up to 24% higher in HIV patients compared with uninfected sex- and age-matched individuals [13,14,15] and large retrospective studies have proved that HIV positive subjects have a higher incidence of cardiovascular events than uninfected individuals [7,16,17]. These cardiovascular diseases are mainly related to impaired vessel wall homeostasis [18]. The mechanisms involved in the genesis of atherosclerosis and subsequent cardiovascular damage in HIV positive patients have still not been elucidated, even though some putative indications were recently reported [10]
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