Nitric oxide-dependent neovascularization role in the lower extremity disease

Curr Pharm Des. 2007;13(35):3591-6. doi: 10.2174/138161207782794103.

Abstract

Peripheral arterial occlusive disease (PAD) describes vascular disorders associated with ischemia and PAD affects about 8 million people in the United States. Moreover, PAD's prevalence can increase dramatically if cardiovascular disease is present. In healthy individuals reducing blood flow through the lower extremity is followed by a physiological process to limit ischemia in the distal tissue. This process is called revascularization and impairing revascularization results in PAD. Studies suggest nitric oxide (NO) maybe involved in the ischemia-dependent hindlimb revascularization process. NO is increased in the ischemic hindlimb and eliminating NO impairs the revascularization process. Moreover, restoring NO improves hindlimb revascularization. NO may be acting through its effects on vascular tone, cell migration, or extracellular matrix degradation. The present review illustrates nitric oxide's critical role in the ischemia-induced hindlimb revascularization. Thus, restoring normal NO levels in diseased arteries may represent a viable therapeutic avenue by supplementing exogenous NO or employing therapeutic strategies to either increase NO synthesis and its messengers or decrease NO catabolism.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology
  • Angiogenesis Inducing Agents / therapeutic use
  • Animals
  • Arterial Occlusive Diseases / complications
  • Arterial Occlusive Diseases / metabolism*
  • Arterial Occlusive Diseases / physiopathology
  • Arterial Occlusive Diseases / therapy
  • Endothelial Cells / transplantation
  • Genetic Therapy / methods
  • Humans
  • Ischemia / etiology*
  • Ischemia / metabolism
  • Ischemia / physiopathology
  • Ischemia / therapy
  • Lower Extremity / blood supply*
  • Neovascularization, Physiologic* / drug effects
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Peripheral Vascular Diseases / complications
  • Peripheral Vascular Diseases / metabolism*
  • Peripheral Vascular Diseases / physiopathology
  • Peripheral Vascular Diseases / therapy
  • Prevalence
  • Risk Factors
  • Signal Transduction
  • Stem Cell Transplantation

Substances

  • Angiogenesis Inducing Agents
  • Nitric Oxide
  • Nitric Oxide Synthase Type III