The Angiopoietin-Tie2 Pathway in Critical Illness

Crit Care Clin. 2020 Apr;36(2):201-216. doi: 10.1016/j.ccc.2019.12.003. Epub 2020 Jan 31.

Abstract

Lethal features of sepsis and acute respiratory distress syndrome (ARDS) relate to the health of small blood vessels. For example, alveolar infiltration with proteinaceous fluid is often driven by breach of the microvascular barrier. Spontaneous thrombus formation within inflamed microvessels exacerbates organ ischemia, and in its final stages, erupts into overt disseminated intravascular coagulation. Disruption of an endothelial signaling axis, the Angiopoietin-Tie2 pathway, may mediate the abrupt transition from microvascular integrity to pathologic disruption. This review summarizes preclinical and clinical results that implicate the Tie2 pathway as a promising target to restore microvascular health in sepsis and ARDS.

Keywords: ARDS; Angiopoietin; Coagulation; Sepsis; Tie2; VE-PTP; Vascular leakage.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / enzymology
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / physiopathology
  • Angiopoietin-1 / metabolism*
  • Angiopoietin-2 / metabolism*
  • Animals
  • Critical Illness*
  • Disseminated Intravascular Coagulation / enzymology
  • Disseminated Intravascular Coagulation / metabolism*
  • Disseminated Intravascular Coagulation / physiopathology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Homeostasis / physiology
  • Humans
  • Receptor, TIE-2 / metabolism*
  • Respiratory Distress Syndrome / enzymology
  • Respiratory Distress Syndrome / metabolism*
  • Respiratory Distress Syndrome / physiopathology
  • Sepsis / enzymology
  • Sepsis / metabolism*
  • Sepsis / physiopathology
  • Signal Transduction

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • Receptor, TIE-2