Regulation of postangiogenic neovessel survival by beta1 and beta3 integrins in collagen and fibrin matrices.
We used the aortic ring model of angiogenesis to investigate the role of beta(1) and beta(3) integrins in postangiogenic vascular survival in collagen and fibrin matrices. Confocal microscopy studies showed that both beta(1) and beta(3) integrins were expressed in endothelial cells and pericytes of sprouting neovessels. Antibody blocking experiments demonstrated that beta(1) integrins but not beta(3) integrins were required for angiogenic sprouting in collagen. Conversely, in fibrin, blockade of both integrins was needed to inhibit angiogenesis whereas treatment with either antibody alone was ineffective. Antibody-mediated blockade of beta(1) but not beta(3) integrins accelerated vascular regression in collagen. In contrast, both anti-beta(1) and -beta(3) integrin antibodies were required to promote neovessel breakdown in fibrin. These results demonstrate that angiogenic sprouting and postangiogenic neovessel survival in collagen are critically dependent on beta(1) integrins. They also indicate that these processes involve a redundant repertoire of beta(1) and beta(3) integrins when angiogenesis occurs in fibrin. Thus, pharmacologic targeting of integrin receptors aimed at blocking neovessel formation and survival must be tailored to the specific extracellular matrix environment in which angiogenesis takes place.
Carnevale
Edvige
E
Department of Pathology, University of Washington, Seattle, WA 98108, USA.
Fogel
Eric
E
Aplin
Alfred C
AC
Gelati
Maurizio
M
Howson
Karen M
KM
Zhu
Wen-Hui
WH
Nicosia
Roberto F
RF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism*; D039661:Integrin beta3 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009924:Organ Culture Techniques; D020286:Pericytes / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000906:Antibodies; D019012:Integrin beta1; D039661:Integrin beta3; D005337:Fibrin; D003094:Collagen