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Arterial “inflammaging” drives vascular calcification in children on dialysis

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Arterial “inflammaging” drives vascular calcification in children on dialysis. / Sanchis, Pilar; Ho, Chin Yee; Liu, Yiwen; Beltran, Leilani E.; Ahmad, Sadia; Jacob, Anne P.; Furmanik, Malgorzata; Laycock, Joanne; Long, David A.; Shroff, Rukshana; Shanahan, Catherine M.

In: Kidney International, Vol. 95, No. 4, 01.04.2019, p. 958-972.

Research output: Contribution to journalArticle

Harvard

Sanchis, P, Ho, CY, Liu, Y, Beltran, LE, Ahmad, S, Jacob, AP, Furmanik, M, Laycock, J, Long, DA, Shroff, R & Shanahan, CM 2019, 'Arterial “inflammaging” drives vascular calcification in children on dialysis', Kidney International, vol. 95, no. 4, pp. 958-972. https://doi.org/10.1016/j.kint.2018.12.014

APA

Sanchis, P., Ho, C. Y., Liu, Y., Beltran, L. E., Ahmad, S., Jacob, A. P., ... Shanahan, C. M. (2019). Arterial “inflammaging” drives vascular calcification in children on dialysis. Kidney International, 95(4), 958-972. https://doi.org/10.1016/j.kint.2018.12.014

Vancouver

Sanchis P, Ho CY, Liu Y, Beltran LE, Ahmad S, Jacob AP et al. Arterial “inflammaging” drives vascular calcification in children on dialysis. Kidney International. 2019 Apr 1;95(4):958-972. https://doi.org/10.1016/j.kint.2018.12.014

Author

Sanchis, Pilar ; Ho, Chin Yee ; Liu, Yiwen ; Beltran, Leilani E. ; Ahmad, Sadia ; Jacob, Anne P. ; Furmanik, Malgorzata ; Laycock, Joanne ; Long, David A. ; Shroff, Rukshana ; Shanahan, Catherine M. / Arterial “inflammaging” drives vascular calcification in children on dialysis. In: Kidney International. 2019 ; Vol. 95, No. 4. pp. 958-972.

Bibtex Download

@article{53fc03df49eb42f48eda74d570bcf761,
title = "Arterial “inflammaging” drives vascular calcification in children on dialysis",
abstract = "Children on dialysis have a cardiovascular mortality risk equivalent to older adults in the general population, with the development of medial vascular calcification, an age-associated pathology. We hypothesized that premature vascular ageing contributes to calcification in children with advanced chronic kidney disease (CKD). Vessels from children with Stage 5 CKD with and without dialysis had evidence of increased oxidative DNA damage. The senescence markers p16 and p21 were also increased in vessels from children on dialysis. Treatment of vessel rings ex vivo with calcifying media increased oxidative DNA damage in vessels from children with Stage 5 CKD, but not in those from healthy controls. Vascular smooth muscle cells cultured from children on dialysis exhibited persistent DNA damage, impaired DNA damage repair, and accelerated senescence. Under calcifying conditions vascular smooth muscle cells from children on dialysis showed increased osteogenic differentiation and calcification. These changes correlated with activation of the senescence-associated secretory phenotype (SASP), an inflammatory phenotype characterized by the secretion of proinflammatory cytokines and growth factors. Blockade of ATM-mediated DNA damage signaling reduced both inflammation and calcification. Clinically, children on dialysis had elevated circulating levels of osteogenic SASP factors that correlated with increased vascular stiffness and coronary artery calcification. These data imply that dysregulated mineral metabolism drives vascular ‘inflammaging’ by promoting oxidative DNA damage, premature senescence, and activation of a pro-inflammatory SASP. Drugs that target DNA damage signaling or eliminate senescent cells may have the potential to prevent vascular calcification in patients with advanced CKD.",
keywords = "aging, calcification, dialysis, senescence, vascular smooth muscle cells",
author = "Pilar Sanchis and Ho, {Chin Yee} and Yiwen Liu and Beltran, {Leilani E.} and Sadia Ahmad and Jacob, {Anne P.} and Malgorzata Furmanik and Joanne Laycock and Long, {David A.} and Rukshana Shroff and Shanahan, {Catherine M.}",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.kint.2018.12.014",
language = "English",
volume = "95",
pages = "958--972",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Arterial “inflammaging” drives vascular calcification in children on dialysis

AU - Sanchis, Pilar

AU - Ho, Chin Yee

AU - Liu, Yiwen

AU - Beltran, Leilani E.

AU - Ahmad, Sadia

AU - Jacob, Anne P.

AU - Furmanik, Malgorzata

AU - Laycock, Joanne

AU - Long, David A.

AU - Shroff, Rukshana

AU - Shanahan, Catherine M.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Children on dialysis have a cardiovascular mortality risk equivalent to older adults in the general population, with the development of medial vascular calcification, an age-associated pathology. We hypothesized that premature vascular ageing contributes to calcification in children with advanced chronic kidney disease (CKD). Vessels from children with Stage 5 CKD with and without dialysis had evidence of increased oxidative DNA damage. The senescence markers p16 and p21 were also increased in vessels from children on dialysis. Treatment of vessel rings ex vivo with calcifying media increased oxidative DNA damage in vessels from children with Stage 5 CKD, but not in those from healthy controls. Vascular smooth muscle cells cultured from children on dialysis exhibited persistent DNA damage, impaired DNA damage repair, and accelerated senescence. Under calcifying conditions vascular smooth muscle cells from children on dialysis showed increased osteogenic differentiation and calcification. These changes correlated with activation of the senescence-associated secretory phenotype (SASP), an inflammatory phenotype characterized by the secretion of proinflammatory cytokines and growth factors. Blockade of ATM-mediated DNA damage signaling reduced both inflammation and calcification. Clinically, children on dialysis had elevated circulating levels of osteogenic SASP factors that correlated with increased vascular stiffness and coronary artery calcification. These data imply that dysregulated mineral metabolism drives vascular ‘inflammaging’ by promoting oxidative DNA damage, premature senescence, and activation of a pro-inflammatory SASP. Drugs that target DNA damage signaling or eliminate senescent cells may have the potential to prevent vascular calcification in patients with advanced CKD.

AB - Children on dialysis have a cardiovascular mortality risk equivalent to older adults in the general population, with the development of medial vascular calcification, an age-associated pathology. We hypothesized that premature vascular ageing contributes to calcification in children with advanced chronic kidney disease (CKD). Vessels from children with Stage 5 CKD with and without dialysis had evidence of increased oxidative DNA damage. The senescence markers p16 and p21 were also increased in vessels from children on dialysis. Treatment of vessel rings ex vivo with calcifying media increased oxidative DNA damage in vessels from children with Stage 5 CKD, but not in those from healthy controls. Vascular smooth muscle cells cultured from children on dialysis exhibited persistent DNA damage, impaired DNA damage repair, and accelerated senescence. Under calcifying conditions vascular smooth muscle cells from children on dialysis showed increased osteogenic differentiation and calcification. These changes correlated with activation of the senescence-associated secretory phenotype (SASP), an inflammatory phenotype characterized by the secretion of proinflammatory cytokines and growth factors. Blockade of ATM-mediated DNA damage signaling reduced both inflammation and calcification. Clinically, children on dialysis had elevated circulating levels of osteogenic SASP factors that correlated with increased vascular stiffness and coronary artery calcification. These data imply that dysregulated mineral metabolism drives vascular ‘inflammaging’ by promoting oxidative DNA damage, premature senescence, and activation of a pro-inflammatory SASP. Drugs that target DNA damage signaling or eliminate senescent cells may have the potential to prevent vascular calcification in patients with advanced CKD.

KW - aging

KW - calcification

KW - dialysis

KW - senescence

KW - vascular smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=85062145445&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2018.12.014

DO - 10.1016/j.kint.2018.12.014

M3 - Article

AN - SCOPUS:85062145445

VL - 95

SP - 958

EP - 972

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -

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