Hyperosmolar state results in increase in PLGF secretion

Abstract

Diabetes mellitus and heart disease are prevalent in the United States and around the world. Especially with the aging population, it is vital to understand the potential risks associated with diabetes, specifically type 2 diabetes mellitus. Hyperglycemia is an established risk factor for heart disease. Our study aims to understand the effects of hyperglycemia on secretion of PLGF, a biomarker for heart disease. In our study, we tested cells in both a hyperglycemic and healthy environment, and used mannitol as a control for hyperosmolarity. We hypothesized that treatment of human vascular cells with H2S would decrease secretion of the pro-atherogenic cytokine, PLGF. We further hypothesized that hyperglycemia (a risk factor for cardiovascular disease) would increase secretion of PLGF by vascular cells and that H2S treatment would reverse this effect.

We found that in both mannitol and hyperglycemic environments, PLGF secretion increased significantly. This implies that hyperosmolarity itself rather than specifically hyperglycemic conditions increase PLGF secretion. Additionally, we found that hydrogen sulfide treatment in increasing doses reversed the increase in PLGF secretion upon hyperglycemic conditions. This supports our hypothesis that treatment of human vascular cells with hydrogen sulfide would decrease secretion of PLGF, and that hyperglycemia would increase secretion of PLGF. These findings are potentially applicable to the hyperosmolar hyperglycemic state sometimes associated with uncontrolled diabetes mellitus. Further understanding of this mechanism could lead to potential clinical treatment of this condition using H2S donating drugs.