Neurovascular protective function of endothelial nitric oxide – recent advances –

Zvonimir S Katusic, Susan A. Austin

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

In the central nervous system endothelial nitric oxide (NO) is an essential molecule responsible for the preservation of the functional integrity of the neurovascular unit. NO causes vasodilatation and is an important inhibitor of platelet aggregation, smooth muscle cell proliferation, and white blood cell adhesion. In addition, endothelium-derived NO exerts anti-inflammatory and pro-angiogenic effects. More recently, it has been recognized that endothelial NO modulates the expression and processing of amyloid precursor protein in cerebrovascular endothelium and neuronal tissue. Studies in endothelial NO synthase (eNOS) knockout mice indicate that endothelial NO functions as a neurovascular protective molecule during aging. Indeed, genetic inactivation of eNOS exacerbates the detrimental effects of aging on cerebrovascular, microglial, and neuronal functions as well as on cognition. These findings suggest that the preservation of healthy endothelium and normal function of eNOS might be important therapeutic targets. Because the beneficial effects of NO are mostly mediated by the activation of guanylate cyclase/cyclic GMP signaling, inhibitors of phosphodiesterase isoforms, or activation of this signaling with exercise, may offer therapeutic opportunities in the prevention and treatment of aging-induced cognitive decline and Alzheimer’s disease. Most recent advances in understanding the molecular mechanisms linking loss of endothelial NO with cognitive decline will be discussed in this review.

Original languageEnglish (US)
Pages (from-to)1499-1503
Number of pages5
JournalCirculation Journal
Volume80
Issue number7
DOIs
StatePublished - 2016

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Keywords

  • Alzheimer’s disease
  • Amyloid precursor protein
  • BACE1
  • Cerebral amyloid angiopathy
  • Hippocampus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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