Aging-associated vascular phenotype in mutant mice with low levels of BubR1

Takuya Matsumoto, Darren J. Baker, Livius V. D'Uscio, Gazi Mozammel, Zvonimir S. Katusic, Jan M. Van Deursen

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

BACKGROUND AND PURPOSE - Aging is a major risk for stroke and a highly complex biological process believed to involve multiple mechanisms. Mutant mice that express low levels of the spindle assembly checkpoint protein BubR1 are known to develop several aging-associated phenotypes at a very young age, including cataracts, lordokyphosis, loss of subcutaneous fat, and impaired wound healing. However, whether BubR1 acts to prevent vascular aging has not yet been established. The present study was designed to investigate the vascular phenotype of mutant mice with low levels of BubR1. METHODS - Morphological, functional, and biochemical analyses were performed on aortas and carotid arteries of 3- to 5-month-old BubR1 mutant mice and wild-type littermates. RESULTS - Arterial wall thickness and inner diameter were significantly reduced in BubR1 mutant mice. Arterial walls of BubR1 mutant mice had low numbers of medial smooth muscle cells. Masson trichrome staining showed profound fibrosis in arterial walls of BubR1 mutant. In agreement with these morphological changes, functional analysis of pressurized isolated carotid arteries of BubR1 mutant mice demonstrated reduced elastic properties. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to the nitric oxide donor DEA-NONOate were significantly reduced in carotid arteries of BubR1 mutant mice. Furthermore, enzymatic activity of nitric oxide synthase and levels of cyclic GMP were significantly reduced in aortas of mutant mice, but production of superoxide anions was significantly increased. CONCLUSIONS - These findings demonstrate that BubR1 insufficiency in mice results in phenotypic changes reminiscent of vascular aging in humans and suggest a role for BubR1 in suppressing the vascular aging process.

Original languageEnglish
Pages (from-to)1050-1056
Number of pages7
JournalStroke
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

Fingerprint

Blood Vessels
Phenotype
Carotid Arteries
Endothelium
Aorta
M Phase Cell Cycle Checkpoints
Biological Phenomena
Nitric Oxide Donors
Subcutaneous Fat
Cyclic GMP
Nitric Oxide Synthase
Superoxides
Wound Healing
Cataract
Acetylcholine
Smooth Muscle Myocytes
Fibrosis
Stroke
Staining and Labeling
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Matsumoto, T., Baker, D. J., D'Uscio, L. V., Mozammel, G., Katusic, Z. S., & Van Deursen, J. M. (2007). Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke, 38(3), 1050-1056. https://doi.org/10.1161/01.STR.0000257967.86132.01

Aging-associated vascular phenotype in mutant mice with low levels of BubR1. / Matsumoto, Takuya; Baker, Darren J.; D'Uscio, Livius V.; Mozammel, Gazi; Katusic, Zvonimir S.; Van Deursen, Jan M.

In: Stroke, Vol. 38, No. 3, 01.03.2007, p. 1050-1056.

Research output: Contribution to journalArticle

Matsumoto, T, Baker, DJ, D'Uscio, LV, Mozammel, G, Katusic, ZS & Van Deursen, JM 2007, 'Aging-associated vascular phenotype in mutant mice with low levels of BubR1', Stroke, vol. 38, no. 3, pp. 1050-1056. https://doi.org/10.1161/01.STR.0000257967.86132.01
Matsumoto T, Baker DJ, D'Uscio LV, Mozammel G, Katusic ZS, Van Deursen JM. Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke. 2007 Mar 1;38(3):1050-1056. https://doi.org/10.1161/01.STR.0000257967.86132.01
Matsumoto, Takuya ; Baker, Darren J. ; D'Uscio, Livius V. ; Mozammel, Gazi ; Katusic, Zvonimir S. ; Van Deursen, Jan M. / Aging-associated vascular phenotype in mutant mice with low levels of BubR1. In: Stroke. 2007 ; Vol. 38, No. 3. pp. 1050-1056.
@article{c835fd2e06604badb4050870593f7a8c,
title = "Aging-associated vascular phenotype in mutant mice with low levels of BubR1",
abstract = "BACKGROUND AND PURPOSE - Aging is a major risk for stroke and a highly complex biological process believed to involve multiple mechanisms. Mutant mice that express low levels of the spindle assembly checkpoint protein BubR1 are known to develop several aging-associated phenotypes at a very young age, including cataracts, lordokyphosis, loss of subcutaneous fat, and impaired wound healing. However, whether BubR1 acts to prevent vascular aging has not yet been established. The present study was designed to investigate the vascular phenotype of mutant mice with low levels of BubR1. METHODS - Morphological, functional, and biochemical analyses were performed on aortas and carotid arteries of 3- to 5-month-old BubR1 mutant mice and wild-type littermates. RESULTS - Arterial wall thickness and inner diameter were significantly reduced in BubR1 mutant mice. Arterial walls of BubR1 mutant mice had low numbers of medial smooth muscle cells. Masson trichrome staining showed profound fibrosis in arterial walls of BubR1 mutant. In agreement with these morphological changes, functional analysis of pressurized isolated carotid arteries of BubR1 mutant mice demonstrated reduced elastic properties. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to the nitric oxide donor DEA-NONOate were significantly reduced in carotid arteries of BubR1 mutant mice. Furthermore, enzymatic activity of nitric oxide synthase and levels of cyclic GMP were significantly reduced in aortas of mutant mice, but production of superoxide anions was significantly increased. CONCLUSIONS - These findings demonstrate that BubR1 insufficiency in mice results in phenotypic changes reminiscent of vascular aging in humans and suggest a role for BubR1 in suppressing the vascular aging process.",
author = "Takuya Matsumoto and Baker, {Darren J.} and D'Uscio, {Livius V.} and Gazi Mozammel and Katusic, {Zvonimir S.} and {Van Deursen}, {Jan M.}",
year = "2007",
month = "3",
day = "1",
doi = "10.1161/01.STR.0000257967.86132.01",
language = "English",
volume = "38",
pages = "1050--1056",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Aging-associated vascular phenotype in mutant mice with low levels of BubR1

AU - Matsumoto, Takuya

AU - Baker, Darren J.

AU - D'Uscio, Livius V.

AU - Mozammel, Gazi

AU - Katusic, Zvonimir S.

AU - Van Deursen, Jan M.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - BACKGROUND AND PURPOSE - Aging is a major risk for stroke and a highly complex biological process believed to involve multiple mechanisms. Mutant mice that express low levels of the spindle assembly checkpoint protein BubR1 are known to develop several aging-associated phenotypes at a very young age, including cataracts, lordokyphosis, loss of subcutaneous fat, and impaired wound healing. However, whether BubR1 acts to prevent vascular aging has not yet been established. The present study was designed to investigate the vascular phenotype of mutant mice with low levels of BubR1. METHODS - Morphological, functional, and biochemical analyses were performed on aortas and carotid arteries of 3- to 5-month-old BubR1 mutant mice and wild-type littermates. RESULTS - Arterial wall thickness and inner diameter were significantly reduced in BubR1 mutant mice. Arterial walls of BubR1 mutant mice had low numbers of medial smooth muscle cells. Masson trichrome staining showed profound fibrosis in arterial walls of BubR1 mutant. In agreement with these morphological changes, functional analysis of pressurized isolated carotid arteries of BubR1 mutant mice demonstrated reduced elastic properties. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to the nitric oxide donor DEA-NONOate were significantly reduced in carotid arteries of BubR1 mutant mice. Furthermore, enzymatic activity of nitric oxide synthase and levels of cyclic GMP were significantly reduced in aortas of mutant mice, but production of superoxide anions was significantly increased. CONCLUSIONS - These findings demonstrate that BubR1 insufficiency in mice results in phenotypic changes reminiscent of vascular aging in humans and suggest a role for BubR1 in suppressing the vascular aging process.

AB - BACKGROUND AND PURPOSE - Aging is a major risk for stroke and a highly complex biological process believed to involve multiple mechanisms. Mutant mice that express low levels of the spindle assembly checkpoint protein BubR1 are known to develop several aging-associated phenotypes at a very young age, including cataracts, lordokyphosis, loss of subcutaneous fat, and impaired wound healing. However, whether BubR1 acts to prevent vascular aging has not yet been established. The present study was designed to investigate the vascular phenotype of mutant mice with low levels of BubR1. METHODS - Morphological, functional, and biochemical analyses were performed on aortas and carotid arteries of 3- to 5-month-old BubR1 mutant mice and wild-type littermates. RESULTS - Arterial wall thickness and inner diameter were significantly reduced in BubR1 mutant mice. Arterial walls of BubR1 mutant mice had low numbers of medial smooth muscle cells. Masson trichrome staining showed profound fibrosis in arterial walls of BubR1 mutant. In agreement with these morphological changes, functional analysis of pressurized isolated carotid arteries of BubR1 mutant mice demonstrated reduced elastic properties. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to the nitric oxide donor DEA-NONOate were significantly reduced in carotid arteries of BubR1 mutant mice. Furthermore, enzymatic activity of nitric oxide synthase and levels of cyclic GMP were significantly reduced in aortas of mutant mice, but production of superoxide anions was significantly increased. CONCLUSIONS - These findings demonstrate that BubR1 insufficiency in mice results in phenotypic changes reminiscent of vascular aging in humans and suggest a role for BubR1 in suppressing the vascular aging process.

UR - http://www.scopus.com/inward/record.url?scp=33947492069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947492069&partnerID=8YFLogxK

U2 - 10.1161/01.STR.0000257967.86132.01

DO - 10.1161/01.STR.0000257967.86132.01

M3 - Article

C2 - 17272762

AN - SCOPUS:33947492069

VL - 38

SP - 1050

EP - 1056

JO - Stroke

JF - Stroke

SN - 0039-2499

IS - 3

ER -