High salt-induced hypertrophy of human vascular smooth muscle cells associated with a decrease in glycocalyx. (December 2018) - Bkaily, Ghassan
Abstract: All health organizations agree that, presently, the average daily salt (sodium chloride) consumption per person has attained almost double the recommended amount. A chronic high salt diet contributes to the increase in blood pressure and to the development of cardiovascular disease. Although our knowledge of hypertension, in general, is abundant, little is known about salt-sensitive hypertension. Here we tested the hypothesis that acute and/or chronic high salt mimicking that present in high-salt sensitive hypertensive patients may induce hypertrophy of human vascular smooth muscle cells (hVSMCs) and their nuclei that are associated with damage to the plasma membrane glycocalyx. Using quantitative 3D confocal microscopy coupled to immunofluorescence techniques, we tested the effects of acute (2–4 days) and chronic (6–16 days) treatments of hVSMCs without (145 mM) or with high (149 mM) extracellular sodium chloride. Our results showed that acute treatment with high salt significantly decreased the relative density of membrane glycocalyx without affecting the whole cell and nuclear volumes of hVSMCs. However, chronic treatments with high salts induced significant decreases in the relative density of glycocalyx accompanied by significant increases in the whole cell and nuclear volumes as well as in the protein/DNA ratio. The high salt-induced hVSMC hypertrophy was associated with a sustained increase in intracellular sodium and calcium. Our results clearly showed that, increasing salt concentration by as little as 4 mM immediately induced damage to the cell membrane glycocalyx leading to chronic Na + and Ca 2+ overloads and hVSMC hypertrophy. The latter may reduce the lumen of arteries leading to an increase in blood pressure. Future identification of the mechanisms that are implicated in a high salt-induced remodeling of hVSMCs may permit the development of new therapeutic interventions for the treatment of high salt-sensitive hypertension and the prevention of the associated cardiovascular diseases.