Cyclic Strain Stimulates Endothelial Cell Proliferation: Characterization of Strain Requirements

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Abstract
Previous studies from our laboratory show that vascular cell biology can be modulated by cyclic strain. However, the precise relationship between cyclic strain and endothelial cell responsiveness remains unclear. The objective of this study was to better characterize this relationship by examining the proliferative response of endothelial cells to sharply defined ranges of strain. This was accomplished by seeding bovine aortic endothelial cells (passages 1–3; N = 9) (10,000 cells/cm2) either on the outer 2/3 (periphery) or the inner 1/3 (center) regions of collagen-coated flexible bottomed wells. The wells were deformed at a frequency of 100 cycles per minute with either -5 kPa vacuum (center, 0–3.2% strain; periphery, 3.2–11% strain) or -20 kPa vacuum (center, 0.37–6.3% strain; periphery, 6.3–25% strain) for up to 5 days. Static, unstretched wells served as controls. At 5 days, endothelial cells subjected to either low (-5 kPa) or high vacuum (-20 kPa), exhibited a stimulated proliferative response in both the center and periphery of the well as compared to the static control (p <0.05). Moreover, at high vacuum, an enhanced rate of proliferation was observed for endothelial cells grown in the center, low strain region compared to the periphery, high strain region. Similar findings were observed at different strain frequencies (10 and 60 cycles per minute). The data support the hypothesis that an optimal strain range exists for endothelial cell proliferation, which if exceeded, causes a dampened proliferative response.