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

Abstract

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.

Osteoglycin as a Potential Biomarker of Mild Kidney Function Impairment in Type 2 Diabetes Patients

“…Therefore, our results suggest that the increased serum OGN levels observed in T2D patients with mildly impaired kidney function (eGFR < 90 mL/min/1.73 m 2 ) are mainly related with renal rather than vascular damage. Endorsing our findings, a recent study observed increased immunostaining of OGN in human atherosclerotic carotid plaques from patients with lower eGFR values [44]. However, further studies are needed to clarify the relationship between OGN and CVD.…”

Peptide location fingerprinting identifies species- and tissue-conserved structural remodelling of proteins as a consequence of ageing and disease

“…Mimecan is a keratan sulphate proteoglycan that has been described as an emerging biomarker of atherosclerosis [103]. In human carotid plaques, its presence was recently shown to be downregulated in vascular smooth muscle cells but upregulated in certain plaque regions (close to collagen fibres and neutral lipids) [104]. The same study also showed a positive correlation between plaque levels of mimecan and age, with higher levels predicting future cardiovascular-related death.…”

A Novel Ex Vivo Approach Based on Proteomics and Biomarkers to Evaluate the Effects of Chrysene, MEHP, and PBDE-47 on Loggerhead Sea Turtles (Caretta caretta)

“…Originally isolated from bovine bone [ 62 ], mimecan/osteoglycin (OGN) is a small leucine-rich proteoglycan, fundamental in collagen fibrillogenesis and in cellular growth, differentiation, and migration control [ 63 ]. Its aberrant expression was described as occurring in several human and other mammal disorders, from cardiovascular risk [ 64 ] to hypothalamic–pituitary–adrenal (HPA) axis dysfunctions [ 65 ], from obesity and related co-morbidities [ 66 , 67 ] to tumorigenesis [ 68 ], cancer [ 69 , 70 , 71 ], and bone homeostasis defects [ 72 ].…”