Endothelin and Diabetic Complications: a Brain-Centric View

Abstract

The global epidemic of diabetes is of significant concern. Diabetes associated vascular disease signifies the principal cause of morbidity and mortality in diabetic patients. It is also the most rapidly increasing risk factor for cognitive impairment, a silent disease that causes loss of creativity, productivity, and quality of life. Small vessel disease in the cerebral vasculature plays a major role in the pathogenesis of cognitive impairment in diabetes. Endothelin system, including endothelin-1 (ET-1) and the receptors (ETA and ETB), is a likely candidate that may be involved in many aspects of the diabetes cerebrovascular disease. In this review, we took a brain-centric approach and discussed the role of the ET system in cerebrovascular and cognitive dysfunction in diabetes.

Impaired Endothelium-Dependent Hyperpolarization Underlies Endothelial Dysfunction during Early Metabolic Challenge: Increased ROS Generation and Possible Interference with NO Function

“…The persistence of the same defective ACh-mediated relaxation pattern in HCfed rat tissues in experiments where equieffective concentrations of PE were used rules out the possibility that the difference in preconstrictor tone affected the ACh response. While a rich body of literature describes a role for the increased production of endothelin-1, acting through ET A receptors, in ED observed in diabetes, obesity, and metabolic syndrome (Harris et al, 2008;Li et al, 2018;Schinzari et al, 2018;Samsamshariat et al, 2019), this did not appear to be the case in aortic rings from HC rats. In vitro exposure to the ET A receptor antagonist atrasentan did not alter aortic response to ACh.…”

Three-dimensional remodeling of functional cerebrovascular architecture and gliovascular unit in leptin receptor-deficient mice

“…Therapeutic strategies that inhibit MMPs expression/activity are beneficial in preventing vascular dysfunction in diabetic models, suggesting the fundamental roles of MMPs in hyperglycemia-induced cerebrovascular remodeling. 7,32 Additionally, MMP-2 activity was upregulated by endothelin-1 (ET-1), a potent vasoconstrictor excessively produced by endothelial cells in GK diabetic rat, 10,74 via activation of its receptor ET A and/or ET B . ET-1 is involved in regulating cerebral autoregulation, myogenic response, cerebrovascular remodeling, neovascularization, as well as neurovascular coupling under both physiological and diabetic conditions.…”

Цукровий Діабет І Мозковий Інсульт: Сучасний Погляд На Проблему

“…Це призводить до зменшення ендотелійзалежного розслаблення судин, збільшення вазоконстрикції, гіперплазії клітин гладеньких м'язів, ремоделювання судин і розвитку атеросклерозу. При цьому ендотеліальна дисфункція супроводжується гіперпродукцією ендотелінів, які мають потужну судинозвужувальну дію [17].…”