Neurovascular protective function of endothelial nitric oxide – recent advances –

Zvonimir S Katusic, Susan A. Austin

Research output: Contribution to journalReview article

14 Citations (Scopus)

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

Fingerprint

Nitric Oxide
Nitric Oxide Synthase
Endothelium
Phosphodiesterase Inhibitors
Amyloid beta-Protein Precursor
Nitric Oxide Synthase Type III
Guanylate Cyclase
Platelet Aggregation Inhibitors
Cyclic GMP
Knockout Mice
Cell Adhesion
Vasodilation
Cognition
Smooth Muscle Myocytes
Alzheimer Disease
Protein Isoforms
Leukocytes
Anti-Inflammatory Agents
Central Nervous System
Cell Proliferation

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Neurovascular protective function of endothelial nitric oxide – recent advances –. / Katusic, Zvonimir S; Austin, Susan A.

In: Circulation Journal, Vol. 80, No. 7, 2016, p. 1499-1503.

Research output: Contribution to journalReview article

@article{d2a902143f9c4139a8f66fc46bb7ef7b,
title = "Neurovascular protective function of endothelial nitric oxide – recent advances –",
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.",
keywords = "Alzheimer’s disease, Amyloid precursor protein, BACE1, Cerebral amyloid angiopathy, Hippocampus",
author = "Katusic, {Zvonimir S} and Austin, {Susan A.}",
year = "2016",
doi = "10.1253/circj.CJ-16-0423",
language = "English (US)",
volume = "80",
pages = "1499--1503",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "7",

}

TY - JOUR

T1 - Neurovascular protective function of endothelial nitric oxide – recent advances –

AU - Katusic, Zvonimir S

AU - Austin, Susan A.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - Amyloid precursor protein

KW - BACE1

KW - Cerebral amyloid angiopathy

KW - Hippocampus

UR - http://www.scopus.com/inward/record.url?scp=84975705393&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975705393&partnerID=8YFLogxK

U2 - 10.1253/circj.CJ-16-0423

DO - 10.1253/circj.CJ-16-0423

M3 - Review article

VL - 80

SP - 1499

EP - 1503

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 7

ER -