Background: Endothelial dysfunction is a hallmark of various cardiovascular diseases. Endothelial Cells (EC) mechanosensor-proteins Syndecan-4 (Syn4), VEGF and KLF2 can translate physical force from vascular microenvironment into biochemical signals. KLF2 regulates the eNOS promoter and acts as eNOS transcription factor increasing its expression. KLF2, Syn4 and VEGF also mediate eNOS phosphorylation which results in higher levels of p-eNOS/NO and inhibition of endothelial adhesion molecules during endothelial injury. Vibroacoustic Stimulation (VATS) - is the noninvasive delivery of sound to the endothelium via penetrating rhythmic stimulation. Preliminary studies show that VATS can induce Syn4, VEGF in rats. The mechanisms underlying the effects of sound on mechanosensors control of eNOS remain incompletely understood. Objective: We hypothesize that VATS can stimulate mechanosensors of human coronary endothelial cells - Syn4, VEGF and KLF2, which will induce eNOS expression and phosphorylation.
Methods: We have used horizontal culture of Human Coronary Endothelial Cells (HCEC) treated by VATS corresponding to shear stress forces in human coronary arteries - 100 Hz, 20 dyn/cm2; 2 days, 2 times a day, 30 min each. HCEC were incubated at 37°C and humidified 5% CO2/95% air. Levels of Syn4, VEGF, KLF2, eNOS and p-eNOS in the cell lysate were analyzed using western blot and fluorescent scanning.
Results: VATS increased Syn4, VEGF, KLF2 levels by 35, 20, and 55% respectively. Levels of eNOS and p-eNOS were also elevated after 2 days of VATS by 22 and 29%.
Conclusions: VATS stimulation of HCEC increases eNOS and p-eNOS possibly via mechanosensors mechanism. These studies support the concept of noninvasive modulation of vascular biology using sound and development of a new noninvasive wearable therapy to improve endothelial dysfunction.