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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death

Author

  • Christoffer Tengryd
  • Signe Holm Nielsen
  • Michele Cavalera
  • Eva Bengtsson
  • Federica Genovese
  • Morten Karsdal
  • Pontus Dunér
  • Marju Orho-Melander
  • Jan Nilsson
  • Andreas Edsfeldt
  • Isabel Gonçalves

Summary, in English

Background and aims: A vulnerable plaque is an atherosclerotic plaque that is rupture-prone with a higher risk to cause cardiovascular symptoms such as myocardial infarction or stroke. Mimecan or osteoglycin is a small leucine-rich proteoglycan, important for collagen fibrillogenesis, that has been implicated in atherosclerotic disease, yet the role of mimecan in human atherosclerotic disease remains unknown. Methods: 196 human atherosclerotic carotid plaques were immunostained for mimecan. Smooth muscle cells, macrophages and intraplaque haemorrhage were also measured with immunohistochemistry. Neutral lipids were stained with Oil Red O and calcium deposits were quantified. Plaque homogenate levels of MCP-1, IL-6 and MIP-1β were measured using a Proximity Extension Assay and MMP-9 levels were measured using Mesoscale. Glycosaminoglycans, collagen and elastin were assessed by colorimetric assays and TGF-β1, β2 and β3 were measured using a multiplex assay. Mimecan gene expression in THP-1 derived macrophages was quantified by qPCR and protein expression in vitro was visualized with immunofluorescence. Cardiovascular events were registered using medical charts and national registers during follow-up. Results: Mimecan correlated positively with plaque area of lipids, macrophages, intraplaque haemorrhage and inversely with smooth muscle cell staining. Mimecan also correlated positively with plaque levels of MMP-9 and MCP-1. Mimecan was upregulated in THP-1 derived macrophages upon stimulation with MCP-1. Patients with high levels of mimecan (above median) had higher risk for cardiovascular death. Conclusions: This study indicates that mimecan is associated with a vulnerable plaque phenotype, possibly regulated by plaque inflammation. In line, plaque levels of mimecan independently predict future cardiovascular death.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Cardiovascular Research - Translational Studies
  • Cancer Infection
  • Division of Microbiology, Immunology and Glycobiology - MIG
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Diabetes - Cardiovascular Disease
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Immunity and Atherosclerosis

Publishing year

2020-11

Language

English

Pages

88-95

Publication/Series

Atherosclerosis

Volume

313

Document type

Journal article

Publisher

Elsevier

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • Atherosclerosis
  • Carotid artery plaque
  • Extracellular matrix proteins
  • Inflammation
  • Proteoglycans

Status

Published

Research group

  • Cardiovascular Research - Translational Studies
  • Cancer Infection
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 0021-9150