HIV-1
can directly interact (and infect ?) ECs. Alternatively, viral products
can induce ECs dysfunctions. Finally, cytokines and growth factors aberrantly
produced by HIV-infected CD4+ cells can target the endothelium altering
its structural and functional integrity
Extracellular Tat protein, the transactivating factor of the human immunodeficiency virus type 1 (HIV-1), is a small cationic polypeptide that can be released from HIV-1 infected cells. Extracellular Tat elicits different biological responses in several types of target cells, including endothelial cells.
In the present paper we will review the various aspects from the lab bench to the bedside that characterize the tight relationship that exists between HIV-1 Tat and endothelium.
Tat interacts with at least three different types of receptors present on the surface of endothelial cells. This leads to the activation of several signal transduction pathways and triggers various biological responses in endothelium. Bioavailability, cell interaction, intracellular signaling, and biological activity of Tat are tightly regulated by components of the extracellular matrix and circulating molecules.
Thus,
Tat is at the center of a complex network of interactions that occur at
the surface of endothelial cells and that greatly affect the functions
of the endothelium, possibly ending in some of the pathological processes
that occur in AIDS patients.
Angiogenesis, 5: 141-151 (2003)