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

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

Atherosclerosis (2020-10-09)
Christoffer Tengryd, Signe Holm Nielsen, Michele Cavalera, Eva Bengtsson, Federica Genovese, Morten Karsdal, Pontus Dunér, Marju Orho-Melander, Jan Nilsson, Andreas Edsfeldt, Isabel Gonçalves
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Transforming Growth Factor-β2 human, TGF-β2, recombinant, expressed in NSO cells, powder, suitable for cell culture
Millipore
MILLIPLEX® TGFß Magnetic Bead 3 Plex Kit - Immunology Multiplex Assay, This MILLIPLEX MAP TGFß (Transforming Growth Factor Beta) - 3 Plex is an Immunology Multiplex Assay is used for the simultaneous quantification of TGFß1, TGFß2 and TGFß3 in the following species: Mouse/Human/Rat/Pig/Horse/Dog/Cat/Non-Human Primate.