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; Katušić, Zvonimir S.; Maehara, Yoshihiko

doi:10.1016/j.jss.2011.03.024

Cited by 21 publications

(21 citation statements)

References 29 publications

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“…The majority of studies have been performed in rat VSMCs and suggest that with age, VSMC proliferation, migration, inflammation and stiffness are increased [for example [18,20,21,25,42]]. On the other hand, studies in human VSMCs are fewer in number and indicate reduced VSMC proliferation with age [30,31]. These discrepancies provoke the questions: which animal model is most appropriate to study VSMC ageing?…”

Section: Discussionmentioning

confidence: 99%

The Effect of Ageing on Vascular Smooth Muscle Cell Behaviour - A Mini-Review

Monk

George

2014

Gerontology

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Ageing is a prominent risk factor for atherosclerosis and cardiovascular disease. Vascular smooth muscle cells (VSMCs) are an integral part of atherosclerotic plaque formation, progression and subsequent rupture. Emerging evidence suggests that VSMC behaviour is modified by age, which in turn may affect disease outcome in the elderly. In this review, we discuss the effect of age on VSMC behaviour, proliferation, migration, apoptosis, inflammation, extracellular matrix synthesis and calcification. In addition, we discuss the multiple signalling factors underlying these behavioural changes including angiotensin-II, matrix metalloproteinases, monocyte chemotactic protein-1, and transforming growth factor-β₁. Understanding the molecular processes underpinning altered VSMC behaviour with age, may lead to the identification of novel therapeutic targets for suppressing atherosclerosis in the elderly population.

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Section: Discussionmentioning

confidence: 99%

The Effect of Ageing on Vascular Smooth Muscle Cell Behaviour - A Mini-Review

Monk

George

2014

Gerontology

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“…61,90,91 The major source of ROS within the cell is as a by-product of oxidative phosphorylation. Mitochondrial DNA damage and dysfunction can increase ROS generation, creating a positive feedback loop.…”

Section: Reactive Oxygen Species and Oxidative Stressmentioning

confidence: 99%

Aging and Atherosclerosis

Wang

Bennett

2012

Circulation Research

683

292

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Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.

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“…Moreover, downregulation of BubR1 via RNA interference reduced the proliferative activity and increased the ROS production in hAoSMC. These results strongly suggest that BUBR1 is involved in the proliferative potential and ROS production in these cells (8). Ikawa-Yoshida et al demonstrated that BUBR1 contributes to oxidative stress-induced aneuploidy in p53-deficient cells (9).…”

mentioning

confidence: 83%

“…Guntani et al revealed that aging-related loss of BUBR1 and subsequent increases of ROS affect the reduction of proliferative capacity of aged smooth muscle cells (8). The expression of BUBR1 and the proliferative capacity of aged human aortic smooth muscle cells (hAoSMC) was reduced with a progression of passages.…”

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confidence: 99%

BUBR1 Insufficiency in Mice Increases Their Sensitivity to Oxidative Stress

Matsuda

Matsumoto

Honma

et al. 2016

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Abstract. Background Budding uninhibited by benzimidazole-related 1 (BUBR1) is a core component of the spindle assembly checkpoint, which monitors whether or not sister chromatids are correctly separated during mitosis. Dysfunction of BUBR1 provokes chromosomal instability, thus leading to aneuploidy (1). Baker et al. generated mice with BubR1 gene mutation with various decreased expression levels of BubR1 due to combinations of wild-type, null, and hypomorphic BubR1 alleles (2-4). The mice that were homogeneous for the hypomorphic allele showed an early onset of aging phenotypes, such as short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat, impaired wound healing, and decreased vascular wall elasticity (2,4). Chromosomal instability, such as aneuploidy, frequently occurred in the cells derived from hypomorphic BubR1 mice, but few mice spontaneously died of cancer under normal conditions (2). Notably, Dai et al. reported that mice with the wild-type allele and null allele were susceptible to carcinogen-induced adenocarcinoma in the lungs and intestines (5), suggesting that aneuploidy caused by the decreased expression of BUBR1 might enhance carcinogeninduced tumorigenesis in mammals.We recently generated a new strain of hypomorphic BubR1 mice in which the expression of BUBR1 is reduced to 20% of the normal level. These low BUBR1-expressing mutant mice (termed BubR1 L/L mice) do not display apparent abnormalities, such as progeria, infertility, shortened lifespan, or structural anomaly in the tissue during growth and development, under normal conditions. Therefore, BubR1 L/L mice are particularly suitable for investigating the precise roles of BUBR1 in age-related diseases, including cancer. Using these mice, we previously demonstrated that decreased expression of BUBR1 completely inhibits intimal hyperplasia after carotid ligation by suppressing the 769 Τhis article is freely accessible online.

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Reduced Proliferation of Aged Human Vascular Smooth Muscle Cells—Role of Oxygen-Derived Free Radicals and BubR1 Expression

Cited by 21 publications

References 29 publications

The Effect of Ageing on Vascular Smooth Muscle Cell Behaviour - A Mini-Review

The Effect of Ageing on Vascular Smooth Muscle Cell Behaviour - A Mini-Review

Aging and Atherosclerosis

BUBR1 Insufficiency in Mice Increases Their Sensitivity to Oxidative Stress

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