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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004639naa a2200505 4500
001oai:DiVA.org:uu-381114
003SwePub
008190405s2019 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:140512227
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3811142 URI
0247 a https://doi.org/10.1016/j.atherosclerosis.2018.12.0272 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1405122272 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Aldi, Silviau Karolinska Institutet4 aut
2451 0a Dual roles of heparanase in human carotid plaque calcification
264 1b ELSEVIER IRELAND LTD,c 2019
338 a print2 rdacarrier
520 a Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-beta-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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Cell- och molekylärbiologi0 (SwePub)301082 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Cell and Molecular Biology0 (SwePub)301082 hsv//eng
653 a Atherosclerosis
653 a Calcification
653 a Heparanase
653 a Bone remodeling
653 a Heparan sulfate proteoglycans
7001 a Eriksson, Linneau Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden4 aut
7001 a Kronqvist, Malinu Karolinska Institutet4 aut
7001 a Lengquist, Marietteu Karolinska Institutet4 aut
7001 a Löfling, Marieu Karolinska Institutet4 aut
7001 a Folkersen, Lasseu Tech Univ Denmark, Ctr Biol Sequence Anal, Copenhagen, Denmark4 aut
7001 a Matic, Ljubica P.u Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden4 aut
7001 a Maegdefessel, Larsu Karolinska Institutet4 aut
7001 a Grinnemo, Karl-Henriku Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden4 aut
7001 a Li, Jin-Pingu Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)jinpili
7001 a Österholm, C.u Karolinska Institutet4 aut
7001 a Hedin, Ulfu Karolinska Institutet4 aut
7102 a Karolinska Institutetb Karolinska Inst, Dept Mol Med & Surg, Bioclinicum J8 20, S-17164 Solna, Sweden4 org
7730 t Atherosclerosisd : ELSEVIER IRELAND LTDg 283, s. 127-136q 283<127-136x 0021-9150x 1879-1484
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-381114
8564 8u https://doi.org/10.1016/j.atherosclerosis.2018.12.027
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:140512227

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