Prolonged cyclic strain inhibits human endothelial cell growth

Area of Science:

• Cardiovascular Biology
• Cell Biology
• Biophysics

Background:

• Vascular endothelium experiences continuous cyclic mechanical strain from pulsatile blood flow.
• Emerging evidence suggests cyclic strain regulates endothelial cell function.

Purpose of the Study:

• To determine if physiologic cyclic strain influences human arterial endothelial cell proliferation.
• To investigate the mechanism of strain-mediated effects on endothelial cells.

Main Methods:

• Human dermal microvascular and human aortic endothelial cells were exposed to cyclic strain (6% at 1 Hz) for up to 7 days.
• Cell proliferation, cell cycle phase, detachment, cytotoxicity, and p21 expression were analyzed.
• Constant and intermittent strain regimens were also tested.

Main Results:

• Prolonged cyclic strain markedly decreased endothelial cell growth.
• The anti-proliferative effect was linked to G2/M cell cycle arrest and p21 induction.
• Inhibition occurred independently of strain regimen (constant or intermittent) and did not involve cytotoxicity or detachment.

Conclusions:

• Chronic physiologic cyclic strain inhibits endothelial cell proliferation.
• This represents a novel mechanism by which hemodynamic forces maintain endothelial cells in a quiescent state.