Pulsatile flow-induced angiogenesis: role of G(i) subunits.

Area of Science:

• Cell Biology
• Vascular Biology
• Biophysics

Background:

• Angiogenesis is crucial for both normal tissue development and pathological conditions.
• Endothelial cells (ECs) are central to angiogenesis, responding to various stimuli.
• Understanding the role of hemodynamic forces like pulsatile flow is key to elucidating angiogenic mechanisms.

Purpose of the Study:

• To investigate the impact of pulsatile flow on in vitro angiogenic activity of endothelial cells.
• To determine the signaling pathways involved in flow-induced angiogenesis.

Main Methods:

• Bovine aortic ECs were subjected to static or pulsatile flow conditions with varying shear stress for 2-24 hours.
• Angiogenesis was quantified by tubule formation on Matrigel.
• EC migration was assessed using a filter migration assay.
• Specific G-protein subunits were manipulated using transfection and inhibitory/activating mutants.

Main Results:

• Pulsatile flow significantly increased EC angiogenesis and migration in a time- and force-dependent manner.
• The maximal effect was observed at 16 hours with a shear stress of 13.2 dyne/cm².
• Pertussis toxin abolished the flow-induced effects, implicating G-protein signaling.
• Activation of G(ialpha)1 or G(ialpha)3 subunits significantly modulated the angiogenic response.

Conclusions:

• Pulsatile flow acts as a potent stimulus for angiogenesis and EC migration.
• The observed effects are primarily mediated by the activation of G(ialpha)1 or G(ialpha)3 subunits.
• G-protein signaling pathways are critical in translating mechanical stimuli into angiogenic responses.