Integrin-associated protein and thrombospondin-1 as endothelial mechanosensitive death mediators.
Recently, it was reported that the offset of hemodynamic forces induces an unusual pattern of apoptosis in vascular endothelium (1). Although the apoptotic trigger covers all cells and is maintained for a longer time period, only few cells become apoptotic. So, in contrast to common apoptosis inducers, the lack of hemodynamic forces initiates only a low basal level of apoptosis, however steadily increases with time, this way preventing the complete vessel destruction upon an only transient offset of blood flow. The molecular means by which the mechanical stimulus and apoptosis are smoothly coupled have now been identified as an autocrine loop of thrombospondin-1 (TSP-1) and the alpha(v)beta(3) integrin/integrin-associated protein (IAP) complex as its receptor. Vascular EC (EC) secrete TSP-1 only in postconfluent static monolayers and not under flow. This also holds true for the IAP whereas the alpha(v)beta(3) integrin is present under static conditions, as well as under flow, assigning the IAP an essential and new switch function in the receptor complex.
Freyberg
M A
MA
Institut für Biochemie, Technische Universität Darmstadt, Petersenstrasse 22, Darmstadt, D-64287, Germany.
Kaiser
D
D
Graf
R
R
Vischer
P
P
Friedl
P
P
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D019030:Receptors, Vitronectin / Q000276:immunology / Q000378:metabolism*; D013314:Stress, Mechanical; D019700:Thrombospondin 1 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D019030:Receptors, Vitronectin; D019700:Thrombospondin 1