Hypoxia plays an important role in
vascular remodeling and directly affects vascular smooth muscle cell (VSMC) functions. VSMC adhesion participates in changes of vascular structure; however, little is known about VSMC adhesion under hypoxic conditions. It was the aim of the present study to investigate the effects of
hypoxia on adhesion mechanisms in human VSMCs. Compared to normoxic cells,
hypoxia (1% O(2), 24h) significantly increased adhesion of VSMCs to
collagen I by 30.2% and
fibronectin by 58.0%. This effect was completely inhibited in the presence of the pharmacological ERK 1/2
mitogen-activated protein kinase (MAPK) pathway inhibitor
PD98059 (30 microM) or the
p38 MAPK inhibitor
SB203580 (1 microM). Basal adhesion of normoxic cells was not affected by pretreatment with
PD98059 and
SB203580.
Hypoxia induced a time-dependent activation of ERK 1/2 and
p38 MAPK activation in human VSMCs, which were completely abolished by
PD98059 or
SB203580, respectively. Since adhesion of VSMCs to
fibronectin and
collagen I involves beta(1)-integrin receptors, we used a blocking antibody against beta(1)-integrin (P5D2) to examine potential effects of
hypoxia on beta(1)-integrins. P5D2 significantly reduced VSMC adhesion to
fibronectin and
collagen I in normoxia and
hypoxia in a comparable manner; however, beta(1)-integrin
protein or
mRNA levels were not affected by
hypoxia. As evidenced by flow cytometry,
hypoxia induced a activation of beta(1)-integrins by exposing an conformationally sensitive
epitope on the beta(1)-subunit. These results demonstrate that
hypoxia enhances adhesion of VSMC on
extracellular matrix proteins by activating beta(1)-integrin.