Carotid Plaque Morphology: Plaque Instability and Correlation with Development of Ischaemic Neurological Events

Introduction: Sex differences in plaque morphology and composition exist; men develop more unstable plaques than women. Yet, stroke kills more women than men. Despite these differences, no sex-specific guidelines for carotid disease management exist. Thus, markers that reflect sex-specific morphological features in the plaque should be explored for better prediction of stroke risk. Pro-inflammatory adipokines, chemerin and resistin, influence vascular function. Herein we are the first to investigate sex differences in the relationship between carotid plaque instability and the expression of these adipokines. Methods: Subjects with ≥50% carotid stenosis scheduled for a carotid endarterectomy were recruited from McGill-affiliated hospitals. Pre-operative plasma chemerin and resistin levels were measured using ELISA. Stability of carotid plaque specimens was assessed by two gold standard histological classifications. Stable and unstable plaques were immunostained for chemerin, chemerin’s receptor (ChemR23), and resistin. Digital and semi-quantifications assessed the % area of expression as well as staining intensity (mild to high) and % of positively stained macrophages/foam cells. Plaque mRNA expression was assessed by quantitative PCR. Sex-hormone analyses are ongoing. Results: Men (n=171) had more unstable plaque features, i.e., greater hemorrhage (P=0.022), lipid core size (P<0.001), inflammation (P=0.007), cap infiltration (P=0.006), and less fibrous tissue (P<0.001) than women (n=79). Circulating chemerin and resistin levels were similar between men and women and no sex differences were observed in relation to plaque instability. The % area of chemerin and resistin staining in the plaque was greater in unstable vs stable plaques in men only (P=0.040; P=0.005, respectively). Similarly, greater intensity in chemerin, ChemR23, and resistin staining was associated with plaque instability in men only (P<0.001; P=0.013; P=0.033, respectively). In contrast, lower resistin plaque mRNA expression was associated with plaque instability in women only (P=0.040). Conclusion: Our results suggest the possibility of a sex-dependent regulatory mechanism underlying the connection between these adipokines and plaque instability.

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The analysis of the connection between plaque morphology of the asymptomatic carotid stenosis and ischemic brain lesions

Vojnosanitetski pregled ◽

10.2298/vsp110519020m ◽

2013 ◽

Vol 70 (11) ◽

pp. 993-998 ◽

Cited By ~ 3

Author(s):

Djordje Milosevic ◽

Janko Pasternak ◽

Vladan Popovic ◽

Dragan Nikolic ◽

Pavle Milosevic ◽

...

Keyword(s):

Risk Factors ◽

Carotid Stenosis ◽

Carotid Plaque ◽

Brain Infarction ◽

Statistical Significance ◽

Brain Parenchyma ◽

Plaque Morphology ◽

Asymptomatic Carotid Stenosis ◽

Asymptomatic Carotid ◽

Silent Brain Infarction

Background/Aim. A certain percentage of patients with asymptomatic carotid stenosis have an unstable carotid plaque. For these patients it is possible to register by modern imaging methods the existence of lesions of the brain parenchyma - the silent brain infarction. These patients have a greater risk of ischemic stroke. The aim of this study was to analyze the connection between the morphology of atherosclerotic carotid plaque in patients with asymptomatic carotid stenosis and the manifestation of silent brain infarction, and to analyze the influence of risk factors for cardiovascular diseases on the occurrence of silent brain infarction and the morphology of carotid plaque. Methods. This retrospective study included patients who had been operated for high grade (> 70%) extracranial atherosclerotic carotid stenosis at the Clinic for Vascular and Transplantation Surgery of the Clinical Center of Vojvodina over a period of 5 years. The patients analyzed had no clinical manifestation of cerebrovascular insufficiency of the carotid artery territory up to the time of operation. The classification of carotid plaque morphology was carried out according to the Gray-Weale classification, after which all the types were subcategorized into two groups: stable and unstable. Brain lesions were verified using preoperative imaging of the brain parenchyma by magnetic resonance. We analyzed ipsilateral lesions of the size > or = 3 mm. Results. Out of a 201 patients 78% had stable plaque and 22% unstable one. Unstable plaque was prevalent in the male patients (male/female ratio = 24.8% : 17.8%), but without a statistically significant difference (p > 0.05). The risk factors (hypertension, nicotinism, hyperlipoproteinemia, and diabetes mellitus) showed no statistically significant impact on carotid plaque morphology and the occurrence of silent brain infarction. Silent brain infarction was detected in 30.8% of the patients. Unstable carotid plaque was found in a larger percentage of patients with silent brain infarction (36.4% : 29.3%) but without a significant statistical difference (p > 0.05). Conclusions. Even though silent brain infarction is more frequent in patients with unstable plaque of carotid bifurication, the difference is of no statistical significance. The effects of the number and type of risk factors bear no statistical significance on the incidence of morphological asymptomatic carotid plaque.

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Association between White Matter Ischaemia and Carotid Plaque Morphology as Defined by High-resolution In Vivo MRI

European Journal of Vascular and Endovascular Surgery ◽

10.1016/j.ejvs.2009.04.005 ◽

2009 ◽

Vol 38 (2) ◽

pp. 149-154 ◽

Cited By ~ 9

Author(s):

A.J. Patterson ◽

J.M. U-King-Im ◽

T.Y. Tang ◽

D.J. Scoffings ◽

S.P.S. Howarth ◽

...

Keyword(s):

White Matter ◽

High Resolution ◽

Carotid Plaque ◽

Plaque Morphology

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IMPACT OF INTENSIVE LIPID LOWERING THERAPY ON CAROTID PLAQUE INSTABILITY ASSESSED BY MRI; CHALLENGER TRIAL: CAROTID PLAQUE IN HUMAN FOR ALL EVALUATIONS WITH AGGRESSIVE ROSUVASTATIN THERAPY – EVALUATION BY MAGNETIC RESONANCE IMAGING

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(14)61046-9 ◽

2014 ◽

Vol 63 (12) ◽

pp. A1046 ◽

Cited By ~ 1

Author(s):

Katsumi Hiroyuki ◽

Miyauchi Daida

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Carotid Plaque ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Resonance Imaging ◽

Therapy Evaluation ◽

Plaque Instability ◽

Lowering Therapy

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The Influence of Carotid Plaque Morphology on the Development of Cerebral Symptoms

Vascular Surgery ◽

10.1177/153857440003400405 ◽

2000 ◽

Vol 34 (4) ◽

pp. 309-318 ◽

Cited By ~ 1

Author(s):

B. Axisa ◽

A. R. Naylor ◽

N. London ◽

P. R. F. Bell ◽

M. M. Thompson

Keyword(s):

Carotid Plaque ◽

Plaque Morphology

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Abstract 110: Carotid Plaque Instability is Associated with an Increase in the Serum Ratio of circularRNA-284 to microRNA-221

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.110 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Hernan Bazan ◽

Ashton Brooks ◽

Daniel Lightell ◽

T. Cooper Woods

Keyword(s):

Ischemic Stroke ◽

Sensitivity And Specificity ◽

Carotid Plaque ◽

Plaque Rupture ◽

Serum Levels ◽

Circular Rna ◽

Cerebrovascular Event ◽

Asymptomatic Group ◽

Plaque Instability ◽

Non Coding Rnas

Introduction: Atherosclerotic cap thinning and plaque instability occur as a result of a decrease in vascular smooth muscle cell proliferation, which is partly regulated by alterations in the expression of non-coding RNAs in the arterial wall. We recently reported that miR-221 expression in the carotid plaque shoulder is reduced immediately following a carotid-related ischemic cerebrovascular event and returns to normal levels after seven days. We hypothesized that changes in the expression of non-coding RNAs within carotid plaques are reflected in the serum of asymptomatic and acutely symptomatic patients with carotid disease. Methods: Serum levels of microRNA (miR) -221 and a circular RNA with potential binding sites for miR-221 (circR-284), were measured using real-time polymerase chain reaction in 41 patients undergoing carotid endarterectomy. Patients were grouped into those who were asymptomatic and those with an acute ischemic cerebrovascular event within the previous 5 days (urgent). Results: miR-221 was significantly lower (0.25 ± 0.11 vs. 1.00 ± 0.31, p = 0.01) while circR-284 was significantly elevated (2.96 ± 1.16 vs. 1.00 ± 0.37, p = 0.06) in the serum of the urgent compared to the asymptomatic group. Serum levels of these RNAs alone did not exhibit favorable sensitivity and specificity for use as a biomarker indicative of carotid-related ischemic stroke. The ratio of serum circR-284:miR-221, however, was significantly elevated in the urgent group [11.7 ± 0.48 vs. 1.0 ± 0.6, p = 0.0002 (Figure, A)]. Furthermore, receiver operator curve analysis of circR-284:miR-221 ratio demonstrated favorable sensitivity and specificity (Figure, B) for detecting carotid plaque rupture and ischemic stroke. Conclusions: Increases in the ratio of serum circR-284:miR-221 has potential as a diagnostic biomarker of carotid-related ischemic stroke. This data also supports the use and development of functionally related pairs of circulating non-coding RNAs as biomarkers.

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