Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus

Nazar Labinskyy, Partha Mukhopadhyay, Janos Toth, Gabor Szalai, Monika Veres, Gyorgy Losonczy, John T. Pinto, Pal Pacher, Praveen Ballabh, Andrej Podlutsky, Steven N. Austad, Anna Csiszar, Zoltan Ungvari

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Vascular aging is characterized by increased oxidative stress and proinflammatory pheno- typic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O .- 2and H 2O 2, endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O .- 2and H 2O 2 production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant up- regulation of inflammatory markers (TNF-α, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflam- matory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxi- dant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume296
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

Peromyscus
Vascular Resistance
Oxidative Stress
Physiological Stress
Gene Expression
Glucose
Blood Vessels
Chemokine CCL2
Intercellular Adhesion Molecule-1
Hyperglycemia
Aorta
Rodentia
Interleukin-6
Mitochondria
Up-Regulation
Arteries
Fibroblasts

Keywords

  • Atherosclerosis
  • Comparative biology
  • Senescence
  • Vascular disease

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus. / Labinskyy, Nazar; Mukhopadhyay, Partha; Toth, Janos; Szalai, Gabor; Veres, Monika; Losonczy, Gyorgy; Pinto, John T.; Pacher, Pal; Ballabh, Praveen; Podlutsky, Andrej; Austad, Steven N.; Csiszar, Anna; Ungvari, Zoltan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 296, No. 4, 04.2009.

Research output: Contribution to journalArticle

Labinskyy, Nazar ; Mukhopadhyay, Partha ; Toth, Janos ; Szalai, Gabor ; Veres, Monika ; Losonczy, Gyorgy ; Pinto, John T. ; Pacher, Pal ; Ballabh, Praveen ; Podlutsky, Andrej ; Austad, Steven N. ; Csiszar, Anna ; Ungvari, Zoltan. / Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus. In: American Journal of Physiology - Heart and Circulatory Physiology. 2009 ; Vol. 296, No. 4.
@article{1b59873ea5f347408e07d3c5ca4de49d,
title = "Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus",
abstract = "Vascular aging is characterized by increased oxidative stress and proinflammatory pheno- typic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O .- 2and H 2O 2, endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O .- 2and H 2O 2 production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant up- regulation of inflammatory markers (TNF-α, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflam- matory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxi- dant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging.",
keywords = "Atherosclerosis, Comparative biology, Senescence, Vascular disease",
author = "Nazar Labinskyy and Partha Mukhopadhyay and Janos Toth and Gabor Szalai and Monika Veres and Gyorgy Losonczy and Pinto, {John T.} and Pal Pacher and Praveen Ballabh and Andrej Podlutsky and Austad, {Steven N.} and Anna Csiszar and Zoltan Ungvari",
year = "2009",
month = "4",
doi = "10.1152/ajpheart.00693.2008",
language = "English (US)",
volume = "296",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in Peromyscus leucopus

AU - Labinskyy, Nazar

AU - Mukhopadhyay, Partha

AU - Toth, Janos

AU - Szalai, Gabor

AU - Veres, Monika

AU - Losonczy, Gyorgy

AU - Pinto, John T.

AU - Pacher, Pal

AU - Ballabh, Praveen

AU - Podlutsky, Andrej

AU - Austad, Steven N.

AU - Csiszar, Anna

AU - Ungvari, Zoltan

PY - 2009/4

Y1 - 2009/4

N2 - Vascular aging is characterized by increased oxidative stress and proinflammatory pheno- typic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O .- 2and H 2O 2, endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O .- 2and H 2O 2 production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant up- regulation of inflammatory markers (TNF-α, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflam- matory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxi- dant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging.

AB - Vascular aging is characterized by increased oxidative stress and proinflammatory pheno- typic alterations. Metabolic stress, such as hyperglycemia in diabetes, is known to increase the production of ROS and promote inflammatory gene expression, accelerating vascular aging. The oxidative stress hypothesis of aging predicts that vascular cells of long-lived species exhibit lower steady-state production of ROS and/or superior resistance to the prooxidant effects of metabolic stress. We tested this hypothesis using two taxonomically related rodents, the white-footed mouse (Peromyscus leucopus) and the house mouse (Mus musculus), which show a more than twofold difference in maximum lifespan potential (8.2 and 3.5 yr, respectively). We compared interspecies differences in steady-state and high glucose (HG; 30 mmol/l)-induced production of O .- 2and H 2O 2, endothelial function, mitochondrial ROS generation, and inflammatory gene expression in cultured aortic segments. In P. leucopus aortas, steady-state endothelial O .- 2and H 2O 2 production and ROS generation by mitochondria were less than in M. musculus vessels. Furthermore, vessels of P. leucopus were more resistant to the prooxidant effects of HG. Primary fibroblasts from P. leucopus also exhibited less steady-state and HG-induced ROS production than M. musculus cells. In M. musculus arteries, HG elicited significant up- regulation of inflammatory markers (TNF-α, IL-6, ICAM-1, VCAM, and monocyte chemoattractant protein-1). In contrast, the proinflam- matory effects of HG were blunted in P. leucopus vessels. Thus, increased life span potential in P. leucopus is associated with decreased cellular ROS generation and increased resistance to prooxi- dant and proinflammatory effects of metabolic stress, which accord with predictions of the oxidative stress hypothesis of aging.

KW - Atherosclerosis

KW - Comparative biology

KW - Senescence

KW - Vascular disease

UR - http://www.scopus.com/inward/record.url?scp=66249145430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66249145430&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00693.2008

DO - 10.1152/ajpheart.00693.2008

M3 - Article

C2 - 19181967

AN - SCOPUS:66249145430

VL - 296

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 4

ER -