Nitric Oxide Alters Human Microvascular Endothelial Cell Response to Cyclic Strain

Area of Science:

• Cardiovascular Biology
• Cell Biology
• Biomedical Engineering

Background:

• Nitric oxide (NO) is crucial for vasodilation and platelet inhibition, produced by endothelial cells via endothelial NO synthase.
• Physical factors influencing NO production are less understood than biochemical agonists.
• Previous studies explored shear stress and transmural pressure effects on NO production.

Purpose of the Study:

• To investigate the impact of cyclic strain on endothelial cell proliferation.
• To analyze the role of nitric oxide (NO) in mediating the cellular response to cyclic strain.
• To examine the combined effects of NO agonists and cyclic strain on endothelial cells.

Main Methods:

• Human microvascular endothelial cells were subjected to varying levels of cyclic strain (0-27%) on deformable plates.
• Nitrogen oxides, cell number, [3H]thymidine incorporation, and total protein were measured.
• Cells were treated with bradykinin (an NO agonist) under cyclic strain conditions.

Main Results:

• 11% cyclic strain increased nitrogen oxides without affecting cell proliferation.
• 27% cyclic strain significantly increased endothelial cell number and proliferation markers.
• Bradykinin with 27% strain elevated NO production and endothelial NO synthase activity but not cell number, despite increased proliferation markers.

Conclusions:

• Endogenous nitric oxide (NO) production by endothelial cells regulates their growth in response to cyclic strain.
• Modulating NO in vivo may offer a strategy to control endothelial cell proliferation in strained vascular regions.
• Cyclic strain influences endothelial cell behavior, with NO playing a key regulatory role.