Dual roles of heparanase in human carotid plaque calcification

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

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Dual roles of heparanase in human carotid plaque calcification. / Aldi, Silvia; Eriksson, Linnéa; Kronqvist, Malin; Lengquist, Mariette; Löfling, Marie; Folkersen, Lasse; Matic, Ljubica P.; Maegdefessel, Lars; Grinnemo, Karl Henrik; Li, Jin Ping; Österholm, C.; Hedin, Ulf.

In: Atherosclerosis, Vol. 283, 2019, p. 127-136.

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

Harvard

Aldi, S, Eriksson, L, Kronqvist, M, Lengquist, M, Löfling, M, Folkersen, L, Matic, LP, Maegdefessel, L, Grinnemo, KH, Li, JP, Österholm, C & Hedin, U 2019, 'Dual roles of heparanase in human carotid plaque calcification', Atherosclerosis, vol. 283, pp. 127-136. https://doi.org/10.1016/j.atherosclerosis.2018.12.027

APA

Aldi, S., Eriksson, L., Kronqvist, M., Lengquist, M., Löfling, M., Folkersen, L., ... Hedin, U. (2019). Dual roles of heparanase in human carotid plaque calcification. Atherosclerosis, 283, 127-136. https://doi.org/10.1016/j.atherosclerosis.2018.12.027

CBE

Aldi S, Eriksson L, Kronqvist M, Lengquist M, Löfling M, Folkersen L, Matic LP, Maegdefessel L, Grinnemo KH, Li JP, Österholm C, Hedin U. 2019. Dual roles of heparanase in human carotid plaque calcification. Atherosclerosis. 283:127-136. https://doi.org/10.1016/j.atherosclerosis.2018.12.027

MLA

Vancouver

Author

Aldi, Silvia ; Eriksson, Linnéa ; Kronqvist, Malin ; Lengquist, Mariette ; Löfling, Marie ; Folkersen, Lasse ; Matic, Ljubica P. ; Maegdefessel, Lars ; Grinnemo, Karl Henrik ; Li, Jin Ping ; Österholm, C. ; Hedin, Ulf. / Dual roles of heparanase in human carotid plaque calcification. In: Atherosclerosis. 2019 ; Vol. 283. pp. 127-136.

Bibtex

@article{888cb583f4d94604ac6817458a10df52,
title = "Dual roles of heparanase in human carotid plaque calcification",
abstract = "Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro. Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively. Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation. Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.",
keywords = "Atherosclerosis, Bone remodeling, Calcification, Heparan sulfate proteoglycans, Heparanase",
author = "Silvia Aldi and Linn{\'e}a Eriksson and Malin Kronqvist and Mariette Lengquist and Marie L{\"o}fling and Lasse Folkersen and Matic, {Ljubica P.} and Lars Maegdefessel and Grinnemo, {Karl Henrik} and Li, {Jin Ping} and C. {\"O}sterholm and Ulf Hedin",
year = "2019",
doi = "10.1016/j.atherosclerosis.2018.12.027",
language = "English",
volume = "283",
pages = "127--136",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Dual roles of heparanase in human carotid plaque calcification

AU - Aldi, Silvia

AU - Eriksson, Linnéa

AU - Kronqvist, Malin

AU - Lengquist, Mariette

AU - Löfling, Marie

AU - Folkersen, Lasse

AU - Matic, Ljubica P.

AU - Maegdefessel, Lars

AU - Grinnemo, Karl Henrik

AU - Li, Jin Ping

AU - Österholm, C.

AU - Hedin, Ulf

PY - 2019

Y1 - 2019

N2 - Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro. Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively. Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation. Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.

AB - Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro. Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively. Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation. Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.

KW - Atherosclerosis

KW - Bone remodeling

KW - Calcification

KW - Heparan sulfate proteoglycans

KW - Heparanase

U2 - 10.1016/j.atherosclerosis.2018.12.027

DO - 10.1016/j.atherosclerosis.2018.12.027

M3 - Journal article

VL - 283

SP - 127

EP - 136

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -