Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Dual roles of heparanase in human carotid plaque calcification

Research output: Contribution to journalJournal articleResearch

  1. Genomic medicine as consumer goods

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Human Disease Variation in the Light of Population Genomics

    Research output: Contribution to journalReviewResearchpeer-review

  3. High-resolution Regulatory Maps Connect Vascular Risk Variants to Disease Related Pathways

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genome-wide analysis yields new loci associating with aortic valve stenosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Novel Mutations in a Chinese Pedigree of Limb Girdle Muscular Dystrophy

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Silvia Aldi
  • Linnéa Eriksson
  • Malin Kronqvist
  • Mariette Lengquist
  • Marie Löfling
  • Lasse Folkersen
  • Ljubica P Matic
  • Lars Maegdefessel
  • Karl-Henrik Grinnemo
  • Jin-Ping Li
  • C Österholm
  • Ulf Hedin
View graph of relations

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
Publication statusE-pub ahead of print - 5 Jan 2019

ID: 56561436