Endothelial heterogeneity associated with regional athero-susceptibility and adaptation to disturbed blood flow in vivo

Semin Thromb Hemost. 2010 Apr;36(3):265-75. doi: 10.1055/s-0030-1253449. Epub 2010 Jun 8.

Abstract

Endothelial phenotypic heterogeneity plays an important role in the susceptibility of the cardiovascular system to disease. Arteries and heart valves are susceptible to chronic inflammatory disease in regions of blood flow disturbance that implicates hemodynamic forces and transport characteristics as prominent influences on endothelial phenotype. By combining in vivo high-throughput genomics (discovery science) and in vitro mechanistic approaches (reductionist science), we present endothelial patho-susceptibility as an imbalance of multiple interrelated pathways that sensitize the cells to pathological change. The recently identified association of endoplasmic reticulum stress with endothelium in regions of flow disturbance is outlined as an important example of susceptible phenotype linked to proinflammatory and oxidative stress pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Arteries / pathology*
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology*
  • Disease Susceptibility
  • Endoplasmic Reticulum / physiology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Gene Expression Profiling
  • Hemorheology*
  • Humans
  • Hypercholesterolemia / complications
  • Models, Biological
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Phenotype
  • Shear Strength
  • Swine
  • Unfolded Protein Response
  • Vasculitis / pathology
  • Vasculitis / physiopathology

Substances

  • NF-kappa B