Reduced proliferation of aged human vascular smooth muscle cells-role of oxygen-derived free radicals and BubR1 expression

Atsushi Guntani, takuya matsumoto, Ryoichi Kyuragi, Kazuomi Iwasa, Toshihiro Onohara, Hiroyuki Itoh, Zvonimir S. Katusic, Yoshihiko Maehara

Research output: Contribution to journalArticle

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Abstract

Background: Aging is a risk factor for atherosclerosis. Recent studies suggest cell cycle events as well as reactive oxygen species (ROS) contribute to vascular cell dysfunction associated with aging. Mice expressing low levels of the spindle assembly checkpoint protein BubR1 develop aging-associated vascular changes at a young age, including decreased smooth muscle cells and increased reactive oxygen species (ROS) production. This study was designed to determine the effect of aging and production of oxygen-derived free radicals on expression of BubR1. Materials and Methods: To assess cell proliferation capacity, human aortic smooth muscle cells (hAoSMC) derived from a young group (17-30 y) or an aged group (57-62 y) were cultured, and cell numbers were directly counted in using a Neubauer chamber. RT-PCR assay was used to evaluate BubR1 expression in cultured hAoSMC stimulated with Angiotensin II or H2O2. Results: No significant difference in BubR1 expression or hAoSMC proliferative ability was demonstrated at passage 5, but both were significantly decreased at passage 8 in the aged hAoSMC. Angiotensin II and H2O2 up-regulated BubR1 expression in young hAoSMC, and the up-regulation was abrogated by a p38 MAPK inhibitor or an inhibitor of the NADH/NADPH oxidase. siRNA against BubR1 reduced proliferative activity and increased ROS production in hAoSMC. Conclusions: These findings demonstrate BubR1 mRNA expression decreases along with proliferation in aged hAoSMC. Aging-related loss of BubR1 and subsequent impairment of reactivity to ROS may explain reduced proliferative capacity of aged smooth muscle cells.

Original languageEnglish
Pages (from-to)143-149
Number of pages7
JournalJournal of Surgical Research
Volume170
Issue number1
DOIs
Publication statusPublished - Sep 1 2011

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Vascular Smooth Muscle
Free Radicals
Smooth Muscle Myocytes
Oxygen
Reactive Oxygen Species
Angiotensin II
Blood Vessels
M Phase Cell Cycle Checkpoints
NADPH Oxidase
p38 Mitogen-Activated Protein Kinases
Small Interfering RNA
Cultured Cells
Atherosclerosis
Cell Cycle
Up-Regulation
Cell Count
Cell Proliferation
Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Surgery

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Reduced proliferation of aged human vascular smooth muscle cells-role of oxygen-derived free radicals and BubR1 expression. / Guntani, Atsushi; matsumoto, takuya; Kyuragi, Ryoichi; Iwasa, Kazuomi; Onohara, Toshihiro; Itoh, Hiroyuki; Katusic, Zvonimir S.; Maehara, Yoshihiko.

In: Journal of Surgical Research, Vol. 170, No. 1, 01.09.2011, p. 143-149.

Research output: Contribution to journalArticle

Guntani, A, matsumoto, T, Kyuragi, R, Iwasa, K, Onohara, T, Itoh, H, Katusic, ZS & Maehara, Y 2011, 'Reduced proliferation of aged human vascular smooth muscle cells-role of oxygen-derived free radicals and BubR1 expression', Journal of Surgical Research, vol. 170, no. 1, pp. 143-149. https://doi.org/10.1016/j.jss.2011.03.024
Guntani, Atsushi ; matsumoto, takuya ; Kyuragi, Ryoichi ; Iwasa, Kazuomi ; Onohara, Toshihiro ; Itoh, Hiroyuki ; Katusic, Zvonimir S. ; Maehara, Yoshihiko. / Reduced proliferation of aged human vascular smooth muscle cells-role of oxygen-derived free radicals and BubR1 expression. In: Journal of Surgical Research. 2011 ; Vol. 170, No. 1. pp. 143-149.
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AU - Iwasa, Kazuomi

AU - Onohara, Toshihiro

AU - Itoh, Hiroyuki

AU - Katusic, Zvonimir S.

AU - Maehara, Yoshihiko

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N2 - Background: Aging is a risk factor for atherosclerosis. Recent studies suggest cell cycle events as well as reactive oxygen species (ROS) contribute to vascular cell dysfunction associated with aging. Mice expressing low levels of the spindle assembly checkpoint protein BubR1 develop aging-associated vascular changes at a young age, including decreased smooth muscle cells and increased reactive oxygen species (ROS) production. This study was designed to determine the effect of aging and production of oxygen-derived free radicals on expression of BubR1. Materials and Methods: To assess cell proliferation capacity, human aortic smooth muscle cells (hAoSMC) derived from a young group (17-30 y) or an aged group (57-62 y) were cultured, and cell numbers were directly counted in using a Neubauer chamber. RT-PCR assay was used to evaluate BubR1 expression in cultured hAoSMC stimulated with Angiotensin II or H2O2. Results: No significant difference in BubR1 expression or hAoSMC proliferative ability was demonstrated at passage 5, but both were significantly decreased at passage 8 in the aged hAoSMC. Angiotensin II and H2O2 up-regulated BubR1 expression in young hAoSMC, and the up-regulation was abrogated by a p38 MAPK inhibitor or an inhibitor of the NADH/NADPH oxidase. siRNA against BubR1 reduced proliferative activity and increased ROS production in hAoSMC. Conclusions: These findings demonstrate BubR1 mRNA expression decreases along with proliferation in aged hAoSMC. Aging-related loss of BubR1 and subsequent impairment of reactivity to ROS may explain reduced proliferative capacity of aged smooth muscle cells.

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