Hyperglycemia Induced Changes in Vascular AKT3 May Inhibit Pressure-Induced Apoptosis in the Rat Inferior Venae Cavae


Background: Vein graft failure after bypass surgery is greatly increase in patients with diabetes mellitus. The cellular mechanisms underlying the cause of this failure are largely unexplored. Protein kinase B/AKT is a mechanically sensitive regulator of cellular growth and apoptosis. Herein we examine whether diabetes affects the regulation of AKT in response to increased venous loading. Methods: Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and the diabetic obese syndrome X Zucker(OSXZ) rats were isolated and incubated ex vivo under basal or pressurized conditions (120 mmHg). Protein expression, basal activation and the ability of increased pressure to activate AKT3 and apoptosis-related signaling were evaluated by immunoblot analysis. Results: Compared to that seen in the non-diabetic lean animals, increased venous pressure in the OSXZ rats was not characterized by increases in APAF-1 concentration, XIAP proteolysis, AIF cleavage, or Bad phosphorylation. This evidence of decreased apoptotic signaling was associated with increased basal p-AKT3 levels (+136% ± 13% P < 0.05 higher in the OSXZ vs. LNZ IVC). Conclusion: These data suggest that diabetes-associated increases in p-AKT3 may alter the ability of the IVC to undergo pressure induced apoptosis-related signaling. Further investigation is required to determine whether these changes are associated with the increased vein graft attrition seen in the diabetic population.

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Rice, K. , Arvapalli, R. and Blough, E. (2015) Hyperglycemia Induced Changes in Vascular AKT3 May Inhibit Pressure-Induced Apoptosis in the Rat Inferior Venae Cavae. Open Journal of Endocrine and Metabolic Diseases, 5, 41-50. doi: 10.4236/ojemd.2015.54006.

Conflicts of Interest

The authors declare no conflicts of interest.


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