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 lesi ons such as Kaposi's sarcoma (KS) are common traits of human immunodeficien cy virus-1 (HIV-1)-infected patients. To investigate possible factors invol ved in acquired immunodeficiency syndrome (AIDS)-associated vasculopathy an d vascular malfunction, expression of vascular endothelial cell growth fact or-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 pro tein secretion were significantly increased in HUT 78 cells incubated with conditioned medium (CM) derived from HIV-1 chronically infected HUT 78 cell s (HIV-TCM) as compared with CM from uninfected cells (TCM), Increase of VE GF-A production in T cells was promoted by inflammatory cytokines (IC) pres ent in HIV-TCM, including tumor necrosis factor alpha (TNF alpha), interfer on gamma (IFN gamma), interleukin-1 beta (IL-1 beta), and IL-6. These IC th at have been shown to be increased in sera of HIV-1-infected patients and t o be increased by HIV-1 infection or cell activation in these individuals a s 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 se ra of HIV-1-infected patients with (mean, 357.1 +/- 197.9 pg/mL) and withou t KS (mean, 256.7 +/- 137.5 pg/mL) as compared with uninfected individuals (mean, 188.6 +/- 91.7 pg/mL). These data suggest that increased secretion o f VEGF-A by T lymphocytes of HIV-1-infected individuals may induce vascular leakage and stimulate proliferation of vascular endothelial cells, which a re hallmarks of AIDS-associated vasculopathy and especially of KS developme nt. (C) 1999 by The American Society of Hematology.