Chronic cigarette smoke exposure triggers a vicious cycle of leukocyte and endothelial-mediated oxidant stress that results in vascular dysfunction
Mohamed Elmahdy, Tamer M. Abdelghany, Craig Hemann, Mohamed G. Ewees, Elsayed M. Mahgoup, Mahmoud S. Eid, Mahmoud T. Shalaan, Yasmin A. Alzarie, Jay L. Zweíer
Abstract
In a chronic model of smoking-induced cardiovascular disease, we define underlying mechanisms of smoking-induced vascular endothelial dysfunction (VED). Smoking exposure triggered VED and hypertension and led to vascular macrophage infiltration with concomitant increase in superoxide and NADPH oxidase levels as early as 16 wk of exposure. This oxidative stress was accompanied by tetrahydrobiopterin depletion, resulting in endothelial nitric oxide synthase uncoupling with further superoxide generation triggering a vicious cycle of oxidative stress and VED.
Topics & Concepts
Oxidative stressNADPH oxidaseEndothelial dysfunctionTetrahydrobiopterinMedicineNitric oxideInternal medicineSuperoxideEndocrinologyChemistryNitric oxide synthaseBiochemistryEnzymeNitric Oxide and Endothelin EffectsEicosanoids and Hypertension PharmacologyNeutrophil, Myeloperoxidase and Oxidative Mechanisms