Integrin beta1 subunit controls mural cell adhesion, spreading, and blood vessel wall stability.
Growth, maturation, and integrity of the blood vessel network require extensive communication between the endothelial cells, which line the vascular lumen, and associated mural cells, namely vascular smooth muscle cells and pericytes. Pericytes extend long processes, make direct contact with the capillary endothelium, and promote vascular quiescence by suppressing angiogenic sprouting. Vascular smooth muscle cells are highly contractile, extracellular matrix-secreting cells that cover arteries and veins and provide them with mechanical stability and elasticity. In the damaged blood vessel wall, for example in atherosclerotic lesions, vascular smooth muscle cells lose their differentiated state and acquire a highly mitotic, so-called "synthetic" phenotype, which is thought to promote pathogenesis. Among other factors, extracellular matrix molecules and integrin family cell-matrix receptors may regulate this phenotypic transition. Here we show that the inactivation of the gene encoding the integrin beta1 subunit (Itgb1) with a Cre-loxP approach in mice leads to mural cell defects and postnatal lethality. Integrin beta1-deficient vascular smooth muscle cells display several hallmarks of the synthetic phenotype: Cell proliferation is enhanced, whereas differentiation and their ability to support blood vessels are compromised. Similarly, mutant pericytes are poorly spread but present in larger numbers. Our analysis of this mutant model shows that integrin beta1-mediated cell-matrix adhesion is a major determinant of the mural cell phenotype.
Abraham
Sabu
S
Vascular Development Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, United Kingdom.
Kogata
Naoko
N
Fässler
Reinhard
R
Adams
Ralf H
RH
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D018390:Gene Targeting; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*
D019012:Integrin beta1