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Published on: June 23, 2011
HIV envelope gp120 activates human arterial smooth muscle cells
A D Schecter1, A B Berman, L Yi
1Zena 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
Summary
The HIV envelope protein gp120 activates arterial smooth muscle cells to initiate blood clotting, contributing to vascular issues in HIV patients. This process involves specific cell receptors and signaling pathways, highlighting a potential mechanism for HIV-related cardiovascular complications.
Area of Science:
- Cardiovascular Science
- Virology
- Immunology
Background:
- Increasing reports of acute coronary thrombotic events in HIV patients.
- Clinical events often attributed to dyslipidemia from protease inhibitor therapy.
- Autopsy studies suggest an underlying arteriopathy in pediatric HIV patients.
Purpose of the Study:
- To investigate the mechanism by which HIV contributes to thrombotic events.
- To determine if HIV proteins activate vascular cells involved in coagulation.
- To elucidate the role of HIV gp120 in smooth muscle cell activation and tissue factor expression.
Main Methods:
- In vitro study using human arterial smooth muscle cells.
- Exposure of cells to HIV envelope protein gp120.
- Analysis of tissue factor expression and coagulation cascade initiation.
- Investigation of coreceptor involvement (CXCR4, CCR5) and CD4 dependence.
- Examination of intracellular signaling pathways (MAPK, PKC, ROS).
Main Results:
- HIV gp120 activates human arterial smooth muscle cells to express tissue factor.
- Tissue factor induction is mediated by CXCR4 and CCR5 coreceptors and requires functional CD4.
- gp120-induced tissue factor expression depends on MAPK and PKC activation, and reactive oxygen species generation.
- Activated smooth muscle cells play a role in coagulation cascade initiation.
Conclusions:
- HIV gp120 directly activates arterial smooth muscle cells, promoting a pro-thrombotic state.
- The interaction involves specific HIV receptors and intracellular signaling pathways.
- This activation mechanism may contribute significantly to vascular, thrombotic, and inflammatory complications in HIV infection.
