Asst Dean for Admissions
Phone: (974) 4492 8305
The endothelium is the single layer of cells that line the lumen of all blood vessels; Communication between endothelial and vascular smooth muscle cells plays a critical role in the regulation of blood flow and blood pressure. Our research efforts seek to clarify the cellular processes that determine endothelial-vascular communication and how disease, notably diabetes, affects endothelial function. The importance of the endothelium in the regulation of cardiovascular function first became apparent as a result of Robert Furchgott’s discovery of the obligatory role played by the endothelium in the regulation of vascular tone, which was reported in the journal Nature in 1980. (Furchgott was one of three scientists awarded a Nobel Prize in 1998 for contributions to the field of nitric oxide research.) We now know that nitric oxide is an important cell signaling molecule that plays several key functions in the cardiovascular system that not only includes the regulation of blood flow, but also inhibition of platelet aggregation as well as an anti-proliferative action on vascular smooth muscle and also counters oxidative stress. Loss of endothelial function, reflecting in part a loss of endothelial nitric oxide (NO), is an early indicator of cardiovascular disease and can be initiated by elevated blood glucose (hyperglycaemia) and lipids as a result, it is assumed, of elevated oxidative stress. Endothelial function also tends to decrease with age. Maintaining a healthy endothelium is thus critical for the health of the cardiovascular system; hence the saying: “You are only as old as your endothelium”.
Nitric oxide is not the only endothelium-derived factor that modulates vascular function and prostacyclin as well as the putative endothelium-derived hyperpolarizing factor (EDHF) both play important, but variable, roles. EDHF may not be a true chemical mediator, but rather reflect low-resistance electrical coupling between endothelial and vascular smooth cells. Studies in our laboratory and notably in collaboration with Dr. Hong Ding (see The Ding Laboratory) have investigated not only endothelial-vascular smooth muscle communication under normal physiological states, but also in animal models of type 1 and type 2 diabetes, genetic ‘knockout’ of endothelial nitric oxide synthase in mice and also in cell culture protocols designed to mimic the diabetic state. Hyperglycaemia is a key trigger for the development of microvascular disease. We have demonstrated that hyperglycaemia has both immediate and long-lasting effects on endothelial function, including changes in the expression of pro- and anti-oxidant enzymes as well as alterations in the expression of endothelial nitric oxide synthase, changes in the pathways that mediate the effects of EDHF as well as a key source of superoxide generation, namely NADPH oxidase. Some aspects of the complexities of endothelial-vascular smooth muscle communication as well as the potential influence from perivascular adipose tissue and diabetes are depicted in the inserted two figures below. (For more details see Ding & Triggle Pflügers Archiv European J. Physiology 2010).
Collaborative research includes work with Dr. Barbara Hempstead (WCMC-NY) on the role of neurotrophins on endothelial function and with Dr. Morley Hollenberg (University of Calgary) on the role of proteinase-activated receptors as well as adipose-derived vasoactive factors in the regulation of vascular tone.
Collaborative research includes work with Dr. Barbara Hempstead (WCMC-NY) on the role of neurotrophins on endothelial function and with Dr. Morley Hollenberg (University of Calgary) on the role of proteinase-activated receptors as well as adipose-derived vasoactive factors in the regulation of vascular tone.
Last modified on
Friday, 20-Jan-2012 15:30:01 AST