Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Apr 15;594(8):2115-24.
doi: 10.1113/JP270923. Epub 2015 Sep 16.

Ageing induced vascular smooth muscle cell senescence in atherosclerosis

Anna K Uryga  1 , Martin R Bennett  1
Affiliations
Review

Ageing induced vascular smooth muscle cell senescence in atherosclerosis

Anna K Uryga et al. J Physiol. .

Abstract

Atherosclerosis is a disease of ageing in that its incidence and prevalence increase with age. However, atherosclerosis is also associated with biological ageing, manifest by a number of typical hallmarks of ageing in the atherosclerotic plaque. Thus, accelerated biological ageing may be superimposed on the effects of chronological ageing in atherosclerosis. Tissue ageing is seen in all cells that comprise the plaque, but particularly in vascular smooth muscle cells (VSMCs). Hallmarks of ageing include evidence of cell senescence, DNA damage (including telomere attrition), mitochondrial dysfunction, a pro-inflammatory secretory phenotype, defects in proteostasis, epigenetic changes, deregulated nutrient sensing, and exhaustion of progenitor cells. In this model, initial damage to DNA (genomic, telomeric, mitochondrial and epigenetic changes) results in a number of cellular responses (cellular senescence, deregulated nutrient sensing and defects in proteostasis). Ultimately, ongoing damage and attempts at repair by continued proliferation overwhelm reparative capacity, causing loss of specialised cell functions, cell death and inflammation. This review summarises the evidence for accelerated biological ageing in atherosclerosis, the functional consequences of cell ageing on cells comprising the plaque, and the causal role that VSMC senescence plays in atherogenesis.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Hallmarks of tissue ageing
A full explanation is provided in the text. Adapted from Lopez‐Otin et al. (2013).
Figure 2
Figure 2. Signalling pathways associated with nutrient excess
A full explanation is provided in the text.
See this image and copyright information in PMC

References

    1. Aavik E, Lumivuori H, Leppanen O, Wirth T, Hakkinen SK, Brasen JH, Beschorner U, Zeller T, Braspenning M, van Criekinge W, Makinen K & Yla‐Herttuala S (2015). Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster. Eur Heart J 36, 993–1000. - PubMed
    1. Acosta JC, Banito A, Wuestefeld T, Georgilis A, Janich P, Morton JP, Athineos D, Kang TW, Lasitschka F, Andrulis M, Pascual G, Morris KJ, Khan S, Jin H, Dharmalingam G, Snijders AP, Carroll T, Capper D, Pritchard C, Inman GJ, Longerich T, Sansom OJ, Benitah SA, Zender L & Gil J (2013). A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15, 978–990. - PMC - PubMed
    1. Acosta JC, O'Loghlen A, Banito A, Guijarro MV, Augert A, Raguz S, Fumagalli M, Da Costa M, Brown C, Popov N, Takatsu Y, Melamed J, d'Adda di Fagagna F, Bernard D, Hernando E & Gil J (2008). Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133, 1006–1018. - PubMed
    1. Allard D, Figg N, Bennett MR & Littlewood TD (2008). Akt regulates the survival of vascular smooth muscle cells via Inhibition of FoxO3a and GSK3. J Biol Chem 283, 19739–19747. - PubMed
    1. Aubert G & Lansdorp PM (2008). Telomeres and aging. Physiol Rev 88, 557–579. - PubMed

Publication types