Date of Award

Spring 4-17-2017

Degree Type

Thesis

Abstract

Elevated glucose and insulin resistance are associated with the prevalence and progression of coronary artery calcification independently of metabolic syndrome. Diabetic patients often exhibit changes in the vessel wall tissue leading to fibrotic collagen and calcific mineral deposition, as opposed to a degenerative tissue remodeling mechanism. Extracellular vesicles (EV) control the deposition of calcific mineral in vascular tissue. Therefore, it was hypothesized that high extracellular glucose concentrations may lead to the release of a large number of EVs by the smooth muscle cells (SMCs) under osteogenic media with high-glucose concentration. To test this, SMCs were placed under normal or osteogenic media with different glucose concentrations (0 g/L-4.5 g/L), and the EVs were analyzed using the Izon qNano. Extracellular calcifications were measured using Alizarin Red S dye, and it was discovered that the absence of glucose results in the lack of extracellular calcification. Conversely, an increase in glucose leads to greater extracellular calcium deposition. These data indicate that the presence of glucose is necessary for extracellular calcification. It was initially suspected that more EVs would be released by SMCs under osteogenic media with high-glucose concentration; however, this was not the case and qNano analysis showed that more EVs were released with osteogenic media that lacked glucose. In addition, EVs in osteogenic high-glucose media presented a greater diameter than those in normal high-glucose media. These results could be consequence of mineral nucleation on EV surface reducing zeta potential. This study indicates a potential role of glucose in vascular wall tissue remodeling.

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