Presentations

Abstract

Introduction:

Type 2 diabetes (T2D) is a complex metabolic disease that presents itself with significant clinical problems such as microvascular endothelial cell dysfunction, which may lead to stroke, myocardial infarction, wound healing delay, and atherosclerosis. While it is established that the immune system is dysregulated in T2D, the impact of dendritic immune cells on these mechanisms is not well understood. This study aims to characterize how dendritic cells contribute to microvascular health dysfunction in T2D conditions.

Methods:

Endothelial cells from C57/BL6 were incubated as control, with ATP, and with ATP + High Glucose/Lipid/Palmitic Acid and assessed for P-ENOS and Total ENOS (both in association with nitric oxide, a key component of vasorelaxation), Beta-Actin, and GAPDH protein expression via Western Blot.

C57/BL6 mice mesenteric arteries were incubated in isolation, with control dendritic cells taken from euthanized C57/BL6 mice, and with dendritic cells incubated under similar control and hyperglycemic High Glucose/Lipid conditions. Endothelial-dependent relaxation and contractility were assessed with wire myography, and compared with wire myography data of this procedure done using DC cells from db/db mice and db/het mice for control and use of mesenteric arteries.

Results:

Incubation of C57/BL6 EC cells with ATP + HG/L/P-Acid mixture presented with decreased expression of detectable proteins in comparison to control incubation and isolated incubation with ATP. C57/BL6 DC cells did not significantly impact mesenteric artery endothelium-dependent relaxation, however, DC cells from db/db mice did impair db/het mesenteric artery endothelium-dependent relaxation.

Conclusion:

Endothelial cell exposure to hyperglycemic conditions inhibited expression of proteins associated with vasorelaxation, and dendritic cells exposed to hyperglycemic conditions in-vivo also led to vasorelaxation impairment, suggesting its contribution to microvascular dysfunction in patients with type 2 diabetes. Additional in-vitro assessments are warranted for further understanding of the vascular role of dendritic cells in type 2 diabetes.