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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1610.)
© 2002 American Heart Association, Inc.

Vascular Biology

Pulsatile Flow–Induced Angiogenesis

Role of G_i Subunits

John P. Cullen; Shariq Sayeed; Rebecca S. Sawai; Nicholas G. Theodorakis; Paul A. Cahill; James V. Sitzmann; Eileen M. Redmond

From the Department of Surgery (J.P.C., S.S., R.S.S., N.G.T., J.V.S., E.M.R.) and the Department of Biochemistry and Biophysics (N.G.T.), University of Rochester Medical Center, Rochester, NY, and the Vascular Biology Research Group (P.A.C.), School of Biotechnology, Dublin City University, Dublin, Ireland.

Correspondence to Dr Eileen M. Redmond, University of Rochester Medical Center, Department of Surgery, Box SURG, 601 Elmwood Ave, Rochester, NY 14642-8410. E-mail eileen_redmond{at}urmc.rochester.edu

Objective— Angiogenesis plays a key role in the growth and function of normal and pathological tissues. We investigated the effect of pulsatile flow on endothelial cell (EC) in vitro angiogenic activity.

Methods and Results— Bovine aortic ECs were exposed to "static" or "flow" (1.2 to 67.0 mL/min, shear stress 1.4 to 19.2 dyne/cm²) conditions for 2 to 24 hours. After exposure, angiogenesis was measured as tubule formation on Matrigel, and EC migration was assessed by filter migration assay. Pulsatile flow increased angiogenesis and EC migration in a temporal and force-dependent manner, with a maximal effect at 16 hours (13.2 dyne/cm²). Pertussis toxin completely inhibited the effect of pulsatile flow on angiogenesis and migration. Transfection of ECs with inhibitory mutants of the subunit of G_i1 or G_i3, but not G_i2, inhibited the flow-induced angiogenic response by 61±2% and 32±6%, respectively, whereas transfection with constitutively activated mutants of the subunit of G_i1 or G_i3, but not G_i2, increased the flow-induced response by 202±23% and 70±4%, respectively. In contrast, inhibition of Gß by the carboxy terminal fragment of ß-adrenergic receptor kinase overexpression increased the flow-induced response by 82±8%.

Conclusions— These results suggest that pulsatile flow stimulates angiogenesis and that this effect is mediated by activation of G_i1 or G_i3, but not Gß, subunits.

Key Words: shear stress • angiogenesis • G proteins • endothelial cells • migration

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