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Cerebrovascular Laboratory

blood flow, endothelium, diabetes...

Cultured human umbilical vein endothelial cells were exposed to high glucose for 6 days and stained for γH2AX (red - a marker of DNA double-strand break formation) and DAPI (blue - a cell nuclei stain)

Research Summary

Blood flow to the brain is controlled by changes in blood vessel diameter which is fine-tuned by an exquisite interplay between vasodilating agents (that increase vessel diameter) and vasoconstricting agents (that decrease vessel diameter). Blood vessels are comprised of a thin lining of endothelial cells and a few layers of adjacent smooth muscle cells. The endothelium produces nitric oxide, a well-known vasodilating agent that can diffuse to the smooth muscle and cause blood vessel dilation and therefore an increase in blood flow. In many disease states (such as hypertension, diabetes and stroke), nitric oxide bioavailability is compromised, resulting in endothelial dysfunction. Our research team is dedicated to understanding the mechanisms associated with endothelial dysfunction, thereby contributing to the development of therapeutic strategies to improve cerebrovascular health.

Research Projects

Obese patients have underlying oxidative stress that leads to cellular senescence whereby cells secrete proinflammatory molecules that promote cardiovascular disease. One way in which cells can become senescent is through disruption of the extremities of their chromosomes, a process called telomere uncapping. Telomere uncapping is a precursor to DNA damage and increased disease risk. We hypothesize that diet-induced obesity leads to DNA damage that primes the vasculature to secondary complications. In this project, DNA damage will be assessed in mice on a normal and high-fat diet.

Diabetes is the fastest growing disease world-wide, with increased mortality and morbidity resulting from the vascular complications. Much of the vascular dysfunction stems from oxidative stress that is generated within the vascular wall, leading to a decrease in the bioavailability of the vasodilating agent, nitric oxide. Sirtuin 1 (SIRT1) is a member of the sirtuin family of proteins that removes the acetyl group (a process called deacetylation) from lysine residues of proteins. Importantly, activation of SIRT1 has been shown to increase nitric oxide availability and reduce oxidative stress. SIRT1 is also a positive regulator of telomere length and has been shown to attenuate telomere shortening associated with ageing. Our laboratory has previously demonstrated that both endothelial nitric oxide synthase and SIRT1 protein expression are significantly blunted during high-fat feeding. This project will assess circulating and vascular telomere length in an animal model of high-fat feeding.

Selected Publications

Dwinovan J, Colella AD, Chegeni N, Chataway TK, Sokoya EM (2017) Proteomic analysis reveals downregulation of housekeeping proteins in the diabetic vascular proteome. Acta Diabetologica, 54(2):171-190

 

Sokoya EM (2015) Resveratrol protects endothelial cells from rapid stretch injury and hypoxia in vitro, Current Drug Therapy, 10:56-64

 

Tajbakhsh S, Aliakbari K, Hussey DJ, Lower KM, Donato AJ, Sokoya EM (2015) Differential telomere shortening in blood versus arteries in an animal model of type 2 diabetes. Journal of Diabetes Research, 2015:153829

 

Tajbakhsh N, Sokoya EM (2014) Compromised EDH-mediated dilations can be rescued by NS309 in obese Zucker rats. Microcirculation, 21:747-753

 

Tajbakhsh N, Sokoya EM (2013) Sirtuin 1 and cerebral vascular function in young obese Zucker rats. European Journal of Pharmacology, 721(1-3):43-8

 

Tajbakhsh N, Sokoya EM (2012) Regulation of cerebral vascular function by sirtuin 1. Microcirculation, 19(4):336-42

 

Burns AR, Phillips SP, Sokoya EM (2012) Pannexin protein expression in the rat middle cerebral artery. Journal of Vascular Research, 49:101-110

 

 

Investigator

  • Elke M Sokoya, BSc(Hons), PhD

Students

  • Samira Tajbakhsh, MBiotech Student (by Research)


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