Title:Endothelin-1 Signaling in Vascular Physiology and Pathophysiology
VOLUME: 12 ISSUE: 2
Author(s):Yessica-Haydee Gomez Sandoval, Mohammed Emehdi Atef, Louis-Olivier Levesque, Yuan Li and Madhu B. Anand-Srivastava
Affiliation:Department of Physiology, Faculty of Medecine, Universite de Montreal, C.P. 6128, Succ. Centre-Ville, Montreal (Quebec) H3C 3J7, Canada.
Keywords:atherosclerosis, diabetes, hypertension, ETA/B receptors, ET-1, ET-1 signaling, ET-1 synthesis.
Abstract:The discovery of endothelin (ET) in 1988 has led to considerable effort to unravel its implication in health and
disease and the mechanisms evoked by ET. ET-1 and related signaling aberrancies are believed to be implicated in the
pathogenesis of diverse cardiovascular diseases, such as hypertension, atherosclerosis, hypertrophy and diabetes. The endothelin
system consists of three potent vasoconstrictive isopeptides, ET-1, ET-2 and ET-3, signaling through two G protein
coupled receptors, ETA and ETB, which are linked to multiple signaling pathways. Activated signaling transduction
pathways include the modulation of the adenylyl cyclase/cAMP pathway through stimulatory (Gs) and inhibitory (Gi) G
proteins, activation of the phosphoinositide pathway through the activation of proteins Gq/11, generation of oxidative
stress, growth factor receptor-related mitogenic events, such as the activation of phosphatidylinositol-3 kinase pathway,
phosphoinositide pathway and activation of the mitogen-activated protein (MAP) kinase cascade. The levels of ETA and
ETB receptors as well as the signaling pathways activated by these receptors are altered in several cardiovascular diseases
including hypertension, hypertrophy, atherosclerosis, diabetes, etc. In this review, we provide an overview of the signaling
events modulated by ET-1 in vascular smooth muscle cells in both physiological and pathological conditions.
