Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment

Tamas Kiss, Priya Balasubramanian, Marta Noa Valcarcel-Ares, Stefano Tarantini, Andriy Yabluchanskiy, Tamas Csipo, Agnes Lipecz, D. Reglodi, Xin A. Zhang, F. Bari, E. Farkas, Anna Csiszar, Zoltan Ungvari

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Age-related impairment of angiogenesis likely has a critical role in cerebromicrovascular rarefaction and development of vascular cognitive impairment and dementia (VCID) in the elderly. Recently, we demonstrated that aging is associated with NAD+ depletion in the vasculature and that administration of NAD+ precursors exerts potent anti-aging vascular effects, rescuing endothelium-mediated vasodilation in the cerebral circulation and improving cerebral blood supply. The present study was designed to elucidate how treatment with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, impacts age-related impairment of endothelial angiogenic processes. Using cerebromicrovascular endothelial cells (CMVECs) isolated from young and aged F344xBN rats, we demonstrated that compared with young cells, aged CMVECs exhibit impaired proliferation, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing [ECIS] technology), impaired ability to form capillary-like structures, and increased oxidative stress. NMN treatment in aged CMVECs significantly improved angiogenic processes and attenuated H2O2 production. We also found that pre-treatment with EX-527, a pharmacological inhibitor of SIRT1, prevented NMN-mediated restoration of angiogenic processes in aged CMVECs. Collectively, we find that normal cellular NAD+ levels are essential for normal endothelial angiogenic processes, suggesting that age-related cellular NAD+ depletion and consequential SIRT1 dysregulation may be a potentially reversible mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging. We recommend that pro-angiogenic effects of NAD+ boosters should be considered in both preclinical and clinical studies.

Original languageEnglish
JournalGeroScience
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Nicotinamide Mononucleotide
NAD
Blood Vessels
Oxidative Stress
Endothelial Cells
Cerebrovascular Circulation
Therapeutics
Aptitude
Electric Impedance
Vasodilation
Wound Healing
Endothelium
Dementia
Cognitive Dysfunction
Cell Proliferation
Pharmacology
Technology

Keywords

  • Endothelial dysfunction
  • Microcirculation
  • NAD precursor
  • Senescence
  • Vascular contributions to cognitive impairment and dementia

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells : a potential mechanism for the prevention of vascular cognitive impairment. / Kiss, Tamas; Balasubramanian, Priya; Valcarcel-Ares, Marta Noa; Tarantini, Stefano; Yabluchanskiy, Andriy; Csipo, Tamas; Lipecz, Agnes; Reglodi, D.; Zhang, Xin A.; Bari, F.; Farkas, E.; Csiszar, Anna; Ungvari, Zoltan.

In: GeroScience, 01.01.2019.

Research output: Contribution to journalArticle

Kiss, Tamas ; Balasubramanian, Priya ; Valcarcel-Ares, Marta Noa ; Tarantini, Stefano ; Yabluchanskiy, Andriy ; Csipo, Tamas ; Lipecz, Agnes ; Reglodi, D. ; Zhang, Xin A. ; Bari, F. ; Farkas, E. ; Csiszar, Anna ; Ungvari, Zoltan. / Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells : a potential mechanism for the prevention of vascular cognitive impairment. In: GeroScience. 2019.
@article{80d4f7e8390147e386a14223614d1ed8,
title = "Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells: a potential mechanism for the prevention of vascular cognitive impairment",
abstract = "Age-related impairment of angiogenesis likely has a critical role in cerebromicrovascular rarefaction and development of vascular cognitive impairment and dementia (VCID) in the elderly. Recently, we demonstrated that aging is associated with NAD+ depletion in the vasculature and that administration of NAD+ precursors exerts potent anti-aging vascular effects, rescuing endothelium-mediated vasodilation in the cerebral circulation and improving cerebral blood supply. The present study was designed to elucidate how treatment with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, impacts age-related impairment of endothelial angiogenic processes. Using cerebromicrovascular endothelial cells (CMVECs) isolated from young and aged F344xBN rats, we demonstrated that compared with young cells, aged CMVECs exhibit impaired proliferation, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing [ECIS] technology), impaired ability to form capillary-like structures, and increased oxidative stress. NMN treatment in aged CMVECs significantly improved angiogenic processes and attenuated H2O2 production. We also found that pre-treatment with EX-527, a pharmacological inhibitor of SIRT1, prevented NMN-mediated restoration of angiogenic processes in aged CMVECs. Collectively, we find that normal cellular NAD+ levels are essential for normal endothelial angiogenic processes, suggesting that age-related cellular NAD+ depletion and consequential SIRT1 dysregulation may be a potentially reversible mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging. We recommend that pro-angiogenic effects of NAD+ boosters should be considered in both preclinical and clinical studies.",
keywords = "Endothelial dysfunction, Microcirculation, NAD precursor, Senescence, Vascular contributions to cognitive impairment and dementia",
author = "Tamas Kiss and Priya Balasubramanian and Valcarcel-Ares, {Marta Noa} and Stefano Tarantini and Andriy Yabluchanskiy and Tamas Csipo and Agnes Lipecz and D. Reglodi and Zhang, {Xin A.} and F. Bari and E. Farkas and Anna Csiszar and Zoltan Ungvari",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s11357-019-00074-2",
language = "English",
journal = "GeroScience",
issn = "2509-2715",
publisher = "Springer International Publishing AG",

}

TY - JOUR

T1 - Nicotinamide mononucleotide (NMN) treatment attenuates oxidative stress and rescues angiogenic capacity in aged cerebromicrovascular endothelial cells

T2 - a potential mechanism for the prevention of vascular cognitive impairment

AU - Kiss, Tamas

AU - Balasubramanian, Priya

AU - Valcarcel-Ares, Marta Noa

AU - Tarantini, Stefano

AU - Yabluchanskiy, Andriy

AU - Csipo, Tamas

AU - Lipecz, Agnes

AU - Reglodi, D.

AU - Zhang, Xin A.

AU - Bari, F.

AU - Farkas, E.

AU - Csiszar, Anna

AU - Ungvari, Zoltan

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Age-related impairment of angiogenesis likely has a critical role in cerebromicrovascular rarefaction and development of vascular cognitive impairment and dementia (VCID) in the elderly. Recently, we demonstrated that aging is associated with NAD+ depletion in the vasculature and that administration of NAD+ precursors exerts potent anti-aging vascular effects, rescuing endothelium-mediated vasodilation in the cerebral circulation and improving cerebral blood supply. The present study was designed to elucidate how treatment with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, impacts age-related impairment of endothelial angiogenic processes. Using cerebromicrovascular endothelial cells (CMVECs) isolated from young and aged F344xBN rats, we demonstrated that compared with young cells, aged CMVECs exhibit impaired proliferation, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing [ECIS] technology), impaired ability to form capillary-like structures, and increased oxidative stress. NMN treatment in aged CMVECs significantly improved angiogenic processes and attenuated H2O2 production. We also found that pre-treatment with EX-527, a pharmacological inhibitor of SIRT1, prevented NMN-mediated restoration of angiogenic processes in aged CMVECs. Collectively, we find that normal cellular NAD+ levels are essential for normal endothelial angiogenic processes, suggesting that age-related cellular NAD+ depletion and consequential SIRT1 dysregulation may be a potentially reversible mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging. We recommend that pro-angiogenic effects of NAD+ boosters should be considered in both preclinical and clinical studies.

AB - Age-related impairment of angiogenesis likely has a critical role in cerebromicrovascular rarefaction and development of vascular cognitive impairment and dementia (VCID) in the elderly. Recently, we demonstrated that aging is associated with NAD+ depletion in the vasculature and that administration of NAD+ precursors exerts potent anti-aging vascular effects, rescuing endothelium-mediated vasodilation in the cerebral circulation and improving cerebral blood supply. The present study was designed to elucidate how treatment with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, impacts age-related impairment of endothelial angiogenic processes. Using cerebromicrovascular endothelial cells (CMVECs) isolated from young and aged F344xBN rats, we demonstrated that compared with young cells, aged CMVECs exhibit impaired proliferation, cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing [ECIS] technology), impaired ability to form capillary-like structures, and increased oxidative stress. NMN treatment in aged CMVECs significantly improved angiogenic processes and attenuated H2O2 production. We also found that pre-treatment with EX-527, a pharmacological inhibitor of SIRT1, prevented NMN-mediated restoration of angiogenic processes in aged CMVECs. Collectively, we find that normal cellular NAD+ levels are essential for normal endothelial angiogenic processes, suggesting that age-related cellular NAD+ depletion and consequential SIRT1 dysregulation may be a potentially reversible mechanism underlying impaired angiogenesis and cerebromicrovascular rarefaction in aging. We recommend that pro-angiogenic effects of NAD+ boosters should be considered in both preclinical and clinical studies.

KW - Endothelial dysfunction

KW - Microcirculation

KW - NAD precursor

KW - Senescence

KW - Vascular contributions to cognitive impairment and dementia

UR - http://www.scopus.com/inward/record.url?scp=85072180911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072180911&partnerID=8YFLogxK

U2 - 10.1007/s11357-019-00074-2

DO - 10.1007/s11357-019-00074-2

M3 - Article

C2 - 31144244

AN - SCOPUS:85072180911

JO - GeroScience

JF - GeroScience

SN - 2509-2715

ER -