HIV envelope gp120 activates human arterial smooth muscle cells.
There have been increasing reports of acute coronary thrombotic events in patients with HIV. Although these clinical events have been attributed primarily to dyslipidemia associated with protease inhibitor therapy, autopsy studies in children with HIV suggest the presence of an underlying arteriopathy. 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 mediated by two biologically relevant coreceptors for HIV infection, CXCR4 and CCR5, and is also dependent on the presence of functional CD4. Induction of 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 important role in the vascular, thrombotic, and inflammatory responses to HIV infection.
Schecter
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AD
Zena and Michael A. Wiener Cardiovascular Institute and Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA. alison.schecter@.mssm.edu
Berman
A B
AB
Yi
L
L
Mosoian
A
A
McManus
C M
CM
Berman
J W
JW
Klotman
M E
ME
Taubman
M B
MB
D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology; D003328:Coronary Thrombosis / Q000209:etiology; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008024:Ligands; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000821:virology; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000633:toxicity; D013925:Thromboplastin / Q000096:biosynthesis
D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D008024:Ligands; D017382:Reactive Oxygen Species; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D013925:Thromboplastin; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases