HIV envelope gp120 activates human arterial smooth muscle cells

There have been increasing reports of acute coronary thrombotic events in p atients with HIV. Although these clinical events have been attributed prima rily to dyslipidemia associated with protease inhibitor therapy, autopsy st udies in children with HIV suggest the presence of an underlying arteriopat hy. This study demonstrates that the HIV envelope protein, gp120, activates human arterial smooth muscle cells to express tissue factor, the initiator of the coagulation cascade. The induction of tissue factor by gp120 is med iated by two biologically relevant coreceptors for HIV infection, CXCR4 and CCR5, and is also dependent on the presence of functional CD4. Induction o f tissue factor by gp120 requires activation of mitogen-activating protein kinases, activation of protein kinase C, and generation of reactive oxygen species, signaling pathways that have protean effects on smooth muscle cell physiology. The activation of smooth muscle cells by gp120 may play an imp ortant role in the vascular, thrombotic, and inflammatory responses to HIV infection.