HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Infection With Human Immunodeficiency Virus-1 Increases Expression of Vascular Endothelial Cell Growth Factor in T Cells: Implications for Acquired Immunodeficiency Syndrome-Associated Vasculopathy

Alterations in the vascular system and the onset of angioproliferative lesions such as Kaposi’s sarcoma (KS) are common traits of human immunodeficiency virus-1 (HIV-1)‐infected patients. To investigate possible factors involved in acquired immunodeficiency syndrome (AIDS)-associated vasculopathy and vascular malfunction, expression of vascular endothelial cell growth factor-A (VEGF-A) was analyzed in HUT 78 T lymphocytes upon infection with HIV-1. VEGF-A was found to be increased in supernatants from infected cells as compared with uninfected cells. In addition, VEGF-A mRNA expression and protein secretion were significantly increased in HUT 78 cells incubated with conditioned medium (CM) derived from HIV-1 chronically infected HUT 78 cells (HIV-TCM) as compared with CM from uninfected cells (TCM). Increase of VEGF-A production in T cells was promoted by inflammatory cytokines (IC) present in HIV-TCM, including tumor necrosis factor a (TNFa), interferon g (IFNg), interleukin-1b (IL-1b), and IL-6. These IC that have been shown to be increased in sera of HIV-1‐infected patients and to be increased by HIV-1 infection or cell activation in these individuals as well as HIV-TCM also increased VEGF-A expression in primary T lymphocytes. Consistent with this, VEGF-A concentrations were found to be higher in sera of HIV-1‐ infected patients with (mean, 357.1 6 197.9 pg/mL) and without KS (mean, 256.7 6 137.5 pg/mL) as compared with uninfected individuals (mean, 188.6 6 91.7 pg/mL). These data suggest that increased secretion of VEGF-A by T lymphocytes of HIV-1‐infected individuals may induce vascular leakage and stimulate proliferation of vascular endothelial cells, which are hallmarks of AIDS-associated vasculopathy and especially of KS development. r 1999 by The American Society of Hematology.