Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Khan, Sheik; Pham, Si M.; Wei, Yunteo; Mateo, Dania; St-Pierre, Melissa; Fletcher, Terace M.; Vázquez-Padrón, Roberto I.

doi:10.1152/ajpheart.00501.2009

Cited by 23 publications

(22 citation statements)

References 44 publications

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“…Immunohistochemical analysis was performed as previously reported [13]. Briefly, 5-µ M paraffin sections were deparaffinized in xylene and rehydrated through a series of graded alcohol washes.…”

Section: Animals and Methodsmentioning

confidence: 99%

A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia

Manning¹,

Skartsis²,

Orta³

et al. 2012

J Vasc Res

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This study describes an alternative arteriovenous fistula (AVF) model in the rat in which the animals develop significant neointimal hyperplasia (NIH) not only at the distal anastomotic site, but also throughout the fistula body. This aortocaval fistula was established by anastomosing the distal end of the renal vein to the abdominal aorta after unilateral nephrectomy. The increased hemodynamic stress resulting from exposing the renal vein to the arterial circulation induced venous NIH as early as 7 days after surgery. This experimental AVF was characterized by the early lack of endothelium, the accumulation of proliferating vascular smooth muscle cells and the neovascularization of the fistula adventitia. In summary, we have described an informative animal model to study the pathobiology of NIH in native AVF.

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Section: Animals and Methodsmentioning

confidence: 99%

A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia

Manning¹,

Skartsis²,

Orta³

et al. 2012

J Vasc Res

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“…33 Finally, somewhat paradoxically but potentially a result of altered cytokine expression, it has been shown that vascular smooth muscle cell senescence is associated with a 2-fold increase in neointimal formation after vascular injury. 34 Taken as a whole, our nascent knowledge of cellular senescence and telomere functionality already attests to the importance of this system in the evolution of the aging vascular phenotype, and we anticipate that the ability to therapeutically manipulate this system would represent a critical advancement in the treatment of atherothrombotic disease in the aging population.…”

Section: Telomere-telomerase Function and Atherothrombotic Diseasementioning

confidence: 99%

“…34 Considérée dans sa globalité, notre connaissance naissante de la sénescence cellulaire et de la fonction exercée par les télomères met d'ores et déjà en lumière l'importance de ce système dans l'évolution du phénotype de vieillissement vasculaire, et il ne fait aucun doute que, si nous parvenions à agir sur ce système à des fins thérapeutiques, nous accomplirions un progrès décisif dans le traitement des affections athérothrombotiques du sujet âgé.…”

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Cellular Senescence, Vascular Disease, and Aging

Kovacic

Moreno²,

Hachinski³

et al. 2011

Circulation

161

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Longevity is a vascular question, which has been well expressed in the axiom that man is only as old as his arteries. To a majority of men death comes primarilyn 2030, when all of the baby boomer generation will be Ն65 years of age, nearly 1 in 5 US residents is expected to be Ͼ65 years of age. By 2050, this age group is projected to more than double in number, from 38.7 million in 2008 to an estimated 88.5 million (Figure 1). 2 Similarly, the population Ն85 years of age is expected to more than triple, from 5.4 million in 2008 to 19 million by 2050. 2 With this aging of the population, the number of people at risk for adverse cardiovascular events, in particular atherothrombosis, stroke, myocardial infarction, and heart failure, will increase dramatically. The importance of these projections is underscored by the fact that currently, although octogenarians represent only 5% of the US population, they account for 20% of all hospitalizations for myocardial infarction and 30% of all myocardial infarction-related deaths. 3 A Looming Aging EpidemicDespite their increased risk of adverse cardiac events, elderly patients are less likely to receive appropriate therapy. This paradox is perhaps related to the fact that elderly patients with cardiovascular disease are more likely to be frail. 4 Heightened concerns that frail older patients may be more susceptible to adverse side effects, particularly in the setting of complex pharmacotherapy, can lead to efficacious therapies being withheld. [5][6][7] As an example, although the relative risk reduction of cholesterol-lowering therapy may be equivalent in the young and elderly, the absolute risk reduction, or number of adverse cardiovascular events prevented, may be significantly greater in elderly patients. 8 This serves as a sobering reminder that even though many exciting advances that might help fight the ravages of old age appear to be at the point of clinical translation, at the present time, clinicians must remain vigilant to ensure the delivery of best medical care to all elderly patients.In this 2-part review, we discuss important pathobiological changes that occur with aging in the cardiovascular system and how they relate to clinical outcomes. Furthermore, we explore areas of scientific progress that may, optimistically, be translatable into targeted clinical strategies to help offset the looming impact of the aging epidemic on morbidity, mortality, and healthcare resource use. Readers should be aware that we do not propose to exhaustively discuss all potential biological players in this complex arena. Rather, we will attempt to selectively highlight novel and important broad aspects of basic and cellular biology and clinical medicine that are of significant relevance to this field. In this first installment, we focus at the basic-science level on key advances in our understanding of the cellular aging process and look to extend these observations to the aging adult vasculature. Telomere Shortening and Cellular Senescence Mechanisms of Telomere-Telomerase Fun...

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“…This proinflammatory profile suggests that senescent or senescent-like events likely occur in the central arterial wall with aging. Emerging evidence indicates that the AAASP likely delivers proinflammatory signals to exaggerate post-injury neoinima formation and enhances the arterial calcification shift with aging [29–31]. …”

Section: Mediamentioning

confidence: 99%

Proinflammation of Aging Central Arteries: A Mini-Review

Wang

Monticone

Lakatta³

2014

Gerontology

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Arterial aging is a cornerstone of organismal aging. The central arterial wall structurally and functionally remodels under chronic proinflammatory stress over a lifetime. The low-grade proinflammation that accompanies advancing age causes arterial wall thickening and stiffening. These structural and functional alterations are consequences of adverse molecular and cellular events, e.g. an increase in local angiotensin II signaling that induces an inflammatory phenotypic shift of endothelial and smooth muscle cells. Thus, interventions to restrict proinflammatory signaling are a rational approach to delay or prevent age-associated adverse arterial remodeling.

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Stress-induced senescence exaggerates postinjury neointimal formation in the old vasculature

Cited by 23 publications

References 44 publications

A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia

A New Arteriovenous Fistula Model to Study the Development of Neointimal Hyperplasia

Cellular Senescence, Vascular Disease, and Aging

Proinflammation of Aging Central Arteries: A Mini-Review

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