Endothelial activation and injury by cigarette smoke exposure

J Biol Regul Homeost Agents. 2011 Apr-Jun;25(2):259-68.

Abstract

Endothelial activation/injury following exposure to cigarette smoke may explain incidence of atherosclerosis and cardiovascular disease in smokers. We investigated cigarette smoke extract (CSE) effects relative to activation, injury, and survival of human umbilical vein endothelial cells (HUVEC) and compared circulating levels of specific endothelial activation markers between smokers and healthy non-smokers before and after smoking cessation. Viability and toxicity of HUVEC were tested by MTT and LDH assay. Release (by endothelial cells) and circulating levels (in smokers) of von Willebrand Factor (vWF), thrombomodulin (TM), was evaluated by ELISA. Incubation with increasing concentrations of CSE reduced the percentage of viable cells, being 33.9%, 23.9% after CSE 4%, 6% respectively. Dose- and time-dependent release of LDH was observed after incubation with CSE. vWF, TM release were assayed after CSE 2% HUVEC stimulation. Significant 42%, 61%, 76% increase in vWF concentration was detected respectively at 30', 60', 120'. Reduction in circulating levels of vWF, from a median value of 144.0% to 123.7%, was observed in the quitters group after smoking cessation. Exposure to cigarette smoke is cytotoxic and induces activation/injury of endothelium in vitro and in vivo. These findings may provide pathogenetic basis by which smoking can predispose to development of atherothrombosis and cardiovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Cell Survival / drug effects
  • Cells, Cultured
  • Complex Mixtures / adverse effects
  • Complex Mixtures / chemistry*
  • Cross-Sectional Studies
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Male
  • Nicotiana / adverse effects
  • Nicotiana / chemistry*
  • Prospective Studies
  • Smoking / adverse effects
  • Smoking / blood*
  • Smoking Cessation
  • Thrombomodulin / blood
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects*
  • Umbilical Veins / metabolism
  • von Willebrand Factor / metabolism

Substances

  • Complex Mixtures
  • Thrombomodulin
  • von Willebrand Factor
  • L-Lactate Dehydrogenase