Low Carotid Calcium Score Is Associated With Higher Levels of Glycosaminoglycans, Tumor Necrosis Factor-Alpha, and Parathyroid Hormone in Human Carotid Plaques

Edsfeldt, Andreas; Dias, Nuno; Elmståhl, Barbara; Müller, Markus; Berg, Katarina; Nitulescu, Mihaela; Persson, Anders; Ekberg, Olle; Gonçalves, Isabel

doi:10.1161/strokeaha.111.620658

Cited by 6 publications

(5 citation statements)

References 12 publications

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“…The connection of high serum concentrations of IL-6 and TNF-α with the presence of unstable plaques assessed in ultrasound examinations has been confirmed by other authors as well [15, 25, 27]. In the present study, no significant differences in TNF-α serum levels depending on the presence of stenosis, its level or clinical manifestation were found, which is in agreement with the results obtained by other authors [23, 28].…”

Section: Discussionsupporting

confidence: 93%

Inflammatory markers in patients with internal carotid artery stenosis

Puz¹,

Lasek–Bal²,

Ziaja³

et al. 2013

aoms

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IntroductionAvailable reports underline the significance of the inflammatory process in the development, progression and destabilisation of atherosclerotic plaques in the internal carotid artery (ICA). The aim of this study was to evaluate the relationship between the degree of ICA stenosis, ultrasound plaque morphology and serum concentration of selected inflammatory markers.Material and methodsSixty-five patients with ICA stenosis > 50% (39 symptomatic) and 30 healthy volunteers were enrolled in the study. Clinical, neurological examination and laboratory evaluation (leucocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, tumour necrosis factor-α (TNF-α), interleukins (1β, 6 and 10), anti-cytomegalovirus IgG antibody titre) were performed. Stenosis grade ≥ 70%, ulcerations on the plaque surface and a hypoechoic (or predominantly hypoechoic) structure of the plaque, obtained by colour-coded duplex examination, were accepted as the characteristics of unstable stenoses.ResultsUnstable ultrasound features of ICA stenosis were found significantly more often in symptomatic than in asymptomatic patients (71.79% vs. 30.71% for stenosis degree ≥ 70%, p = 0.001 and 61.23% vs. 38.46% for unstable plaque morphology, p = 0.01). Patients with ICA stenosis had significantly higher serum concentrations of interleukin-6, fibrinogen, ESR and higher CRP values than the individuals from the control group (p = 0.001, p = 0.009, p = 0.036, p = 0.009 respectively). Patients with unstable plaques structure had significantly higher concentrations of TNF-α, interleukin-6, fibrinogen, higher number of leukocytes, monocytes and higher CRP values than patients with stable plaques (p = 0.008, p = 0.049, p = 0.012, p = 0.0002, p = 0.006, p = 0.0003 respectively). No significant differences in above-mentioned parameters between the groups with stenosis < 70% and ≥ 70% were found.ConclusionsThere is a relationship between the activity of the selected inflammatory markers in serum and atherosclerotic unstable internal carotid artery stenosis. There is no relationship between serum concentration of inflammatory markers and degree of carotid artery stenosis.

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Section: Discussionsupporting

confidence: 93%

Inflammatory markers in patients with internal carotid artery stenosis

Puz¹,

Lasek–Bal²,

Ziaja³

et al. 2013

aoms

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“…In a recent systematic review of 24 studies, it has been reported that clinically symptomatic carotid plaques have less calcium content than asymptomatic ones [1]. Of interest was this recent report that carotid plaques not so rich in calcium had higher expression of proinflammatory cytokines [2]. These findings support earlier observations that calcium may have a plaque stabilizing role [3], [4].…”

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confidence: 72%

How Does Juxtaluminal Calcium Affect Critical Mechanical Conditions in Carotid Atherosclerotic Plaque? An Exploratory Study

Zhang

Sadat

et al. 2014

IEEE Trans. Biomed. Eng.

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The impact of calcification on the carotid atherosclerotic plaque vulnerability remains controversial and unclear. This study assesses the critical mechanical conditions induced by the calcium at the lumen surface, i.e., juxtaluminal calcification (JLCa), within human carotid atherosclerotic plaque. Eleven patients with evidence of JLCa were included for the analysis. The plaque geometry was reconstructed based on computed tomography and magnetic resonance images and 3-D fluid-structure interaction simulation was used for mechanical analysis. The presence of JLCa increased local stresses compared to when calcification was artificially covered with a 0.2-mm-thick fibrous cap (107.87 kPa [76.99, 129.14] versus 63.17 kPa [34.55, 75.13]; Median, [interquartile range]; ). Stretch ratio decreased from 1.18 [1.07, 1.27] to 1.13 [1.10, 1.18] (p = 0.03). The presence of JLCa significantly elevates local stress and stretch level. Further exploration of this plaque feature is warranted as a possible risk factor causing plaque vulnerability.

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“…Sections were then fixed with Histochoice (Amresco, Solon, OH, USA) and stained for smooth muscle cells (smooth muscle α-actin), macrophages (CD68), neutral lipids (Oil Red O) and intraplaque haemorrhage (Glycophorin A) as previously described [9,10]. Calcified areas in plaques were quantified as described previously [11]. Collagen fibers (yellow) were assessed using Russell-Movat Pentachrome staining.…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

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

et al. 2020

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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.

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Low Carotid Calcium Score Is Associated With Higher Levels of Glycosaminoglycans, Tumor Necrosis Factor-Alpha, and Parathyroid Hormone in Human Carotid Plaques

Cited by 6 publications

References 12 publications

Inflammatory markers in patients with internal carotid artery stenosis

Inflammatory markers in patients with internal carotid artery stenosis

How Does Juxtaluminal Calcium Affect Critical Mechanical Conditions in Carotid Atherosclerotic Plaque? An Exploratory Study

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

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