Effect of H2S on PLGF secretion by human vascular cells
Abstract
Angiogenesis is the growth of new blood vessels that plays an essential role in development and wound healing as well as during coronary revascularization, which is necessary to repair tissues following a myocardial ischemic event. Arteriogenesis is the increase in diameter and wall thickness of pre-existing blood vessels to provide blood flow to otherwise deprived tissue. This can be beneficial through widening collateral vessels when occlusions and ischemia occur. PLGF is a multifunctional angiogenic and arteriogenic cytokine that is secreted as a compensatory response following vascular occlusion. PLGF is unique in that it drives both physiological (arteriogenesis) and pathological (atherosclerosis) processes. Atherosclerosis is a gradual process whereby arteries become increasingly narrow due to the presence of fatty plaques in the arterial wall that protrude into the vessel space and compromise blood flow to distal regions. PLGF contributes to early progression of atherosclerosis and serves as a clinical biomarker for cardiovascular disease. Hyperglycemia is a well-established risk factor for cardiovascular disease due to glucose-driven damage to the endothelial cells lining the vessel wall, as well as increased osmolarity in the vessel. H2S is endogenously produced in the human body by the enzyme cystathionine gamma lyase (CSE) in vascular cells. H2S has been shown to be pro-angiogenic, anti-inflammatory, and vasodilatory. The effect of H2S on arteriogenesis, as well as combating atherosclerosis is unknown. Since low levels of hydrogen sulfide (H2S) have recently been shown to be protective to the cardiovascular system, we hypothesized that treatment of human vascular cells with H2S would increase secretion of the pro-arteriogenic cytokine, PLGF. Based on conclusions from our first hypothesis, we further hypothesized that hyperglycemia would increase secretion of PLGF and that H2S treatment would reverse this effect. We found that H2S decreased PLGF secretion at 6 hours post treatment in human vascular smooth muscle and endothelial cells under basal conditions. In addition, we found that hyperosmolarity-induced PLGF secretion was reversed by H2S treatment. We conclude that H2S treatment reduces the secretion of PLGF and therefore protects vascular cells from a PLGF-driven pro-atherogenic environment. Further studies are needed to elucidate the mechanism whereby H2S affects PLGF secretion under basal and hyperosmolar conditions.