Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Circ Res. 2016 Feb 19;118(4):620-36. doi: 10.1161/CIRCRESAHA.115.306301.

Abstract

Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.

Keywords: atherosclerosis; endothelial cells; homeostasis; risk factors; thrombosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology
  • Atherosclerosis / therapy
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Hemodynamics
  • Humans
  • Inflammation Mediators / metabolism
  • Nitric Oxide / metabolism
  • Phenotype
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Signal Transduction

Substances

  • Inflammation Mediators
  • Nitric Oxide