Redox-dependent mechanisms in coronary collateral growth: the "redox window" hypothesis

Antioxid Redox Signal. 2009 Aug;11(8):1961-74. doi: 10.1089/ars.2009.2476.

Abstract

This review addresses the complexity of coronary collateral growth from the aspect of redox signaling and introduces the concept of a "redox window" in the context of collateral growth. In essence, the redox window constitutes a range in the redox state of cells, which not only is permissive for the actions of growth factors but also amplifies their actions. The interactions of redox-dependent signaling with growth factors are well established through the actions of many redox-dependent kinases (e.g., Akt and p38 mitogen-activated protein kinase). The initial changes in cellular redox can be induced by a variety of events, from the oxidative burst during reperfusion after ischemia, to recruitment of various types of inflammatory cells capable of producing reactive oxygen species. Any event that "upsets" the normal redox equilibrium is capable of amplifying growth. However, extremes of the redox window, oxidative and reductive stresses, are associated with diminished growth-factor signaling and reduced activation of redox-dependent kinases. This concept of a redox window helps to explain why the clinical trials aimed at stimulating coronary collateral growth, the "therapeutic angiogenesis trials," failed. However, understanding of redox signaling in the context of coronary collateral growth could provide new paradigms for stimulating collateral growth in patients.

Publication types

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

MeSH terms

  • Angiotensin II / physiology
  • Animals
  • Coronary Vessels / growth & development*
  • Coronary Vessels / metabolism
  • Humans
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Angiotensin II