Dual roles of heparanase in human carotid plaque calcification

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

  • Author: Aldi, Silvia

    Karolinska Institutet, Sweden

  • Author: Eriksson, Linnéa

    Karolinska Institutet, Sweden

  • Author: Kronqvist, Malin

    Karolinska Institutet, Sweden

  • Author: Lengquist, Mariette

    Karolinska Institutet, Sweden

  • Author: Löfling, Marie

    Karolinska Institutet, Sweden

  • Author: Folkersen, Lasse

    Department of Health Technology, Technical University of Denmark

  • Author: Matic, Ljubica P.

    Karolinska Institutet, Sweden

  • Author: Maegdefessel, Lars

    Technical University of Munich, Germany

  • Author: Grinnemo, Karl Henrik

    Karolinska Institutet, Sweden

  • Author: Li, Jin Ping

    Uppsala University, Sweden

  • Author: Österholm, C.

    Karolinska Institutet, Sweden

  • Author: Hedin, Ulf

    Karolinska Institutet, Sweden

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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.

Original languageEnglish
JournalAtherosclerosis
Volume283
Pages (from-to)127-136
Number of pages10
ISSN0021-9150
DOIs
Publication statusPublished - 2019
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Atherosclerosis, Bone remodeling, Calcification, Heparan sulfate proteoglycans, Heparanase

ID: 171934609