Abstract 453: Chemerin and Resistin Expression in Carotid Plaque Instability

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Robert-James Doonan ◽  
Samantha Steinmetz-Wood ◽  
Karina Gasbarrino ◽  
Huaien Zheng ◽  
Chi Lai ◽  
...  

Objective: Chemerin and resistin are pro-inflammatory cytokines that have been shown to play a role in atherosclerosis and coronary artery disease. However, their association with carotid atherosclerosis has not been investigated. We sought to assess the relationship between a) circulating chemerin/resistin levels and cerebrovascular symptomatology, and b) chemerin/resistin plaque expression and carotid plaque instability. Methods: Patients scheduled for carotid endarterectomy were recruited from the Royal Victoria and Jewish General hospitals, Montreal, Canada. Blood was drawn pre-operatively and plasma resistin and chemerin were measured using ELISA. Maximum stenosis sections were stained with hematoxylin and eosin and immunostained with anti-CD3 and anti-CD68. Two vascular pathologists used semi-quantitative scales to classify plaque foam cells and inflammatory cells as well as overall plaque instability. RNA was isolated from the area of maximum stenosis, reverse transcribed, and qPCR was performed to measure chemerin and resistin expression. Kruskal-Wallis or Mann-Whitney U tests were used to evaluate differences in resistin and chemerin between groups. Results: In this ongoing study we recruited 169 patients (66.1% men, 74.5% symptomatic) with a mean±SD age of 70.0±9.3 years. To date all 169 patients had blood samples drawn and 100 had plaque chemerin and resistin expression assessed. Symptomatic patients had higher plasma chemerin (230 (179.0-261.3) vs. 201.4 (175.8-228.1) ng/ml, P=0.08) and resistin levels (12.7 (10.2-17.7) vs. 10.8 (7.1-16.0) ng/ml, P=0.02) when compared with asymptomatic patients. Chemerin plaque expression was decreased in plaques with greater number of foam cells and inflammatory cells and in plaques with greater overall instability. Resistin plaque expression was also decreased in plaques with a greater number of foam cells and inflammatory cells. Conclusions: Circulating chemerin and resistin levels are increased in symptomatic patients. Intraplaque chemerin and resistin expression is inversely related to the number of plaque inflammatory cells and instability. Our ongoing work will determine the underlying mechanisms linking chemerin and resistin with atherosclerotic plaque instability.

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Karina Gasbarrino ◽  
Russell Yanofsky ◽  
Carina Sancho ◽  
Fanny Jaunet ◽  
Huaien Zheng ◽  
...  

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.


VASA ◽  
2016 ◽  
Vol 45 (5) ◽  
pp. 411-416 ◽  
Author(s):  
Carina Wendorff ◽  
Heiko Wendorff ◽  
Andreas Kuehnl ◽  
Pavlos Tsantilas ◽  
Michael Kallmayer ◽  
...  

Abstract. Background: It is still a controversial issue whether carotid endarterectomy (CEA) for asymptomatic carotid stenosis is superior to best medical treatment. The aim of this study was therefore to analyze the impact of sex and age on carotid plaque instability in asymptomatic patients undergoing CEA. Patients and methods: Atherosclerotic plaques from 465 asymptomatic patients with high-grade carotid artery stenosis (2004 - 2013) at the Munich Vascular Biobank were analyzed. Ascertainment of lesion stability/instability was performed on formalin-fixed paraffin-embedded tissue samples using hematoxylin-eosin and elastic van Gieson staining. Unstable plaques were considered lesions with a fibrous cap < 200 µm overlaying lipid-rich atheroma. Results: The average age of the patients was 69.3 ± 8.2 years. Independent of age, asymptomatic men had in total more frequently unstable plaques in contrast to women (41 % versus 52%, p = 0.042). No differences were found in plaque instability between age-related quartiles (< 65, 65- 69, 70 - 74, > 74 years) for female sex (p = 0.422). In men, a continuous increase in plaque instability with age was observed, without achieving statistical significance (p = 0.125). The greatest differences between male and female sex were found in the last quartile (> 74 years), without achieving statistical significance (p = 0.053). The chance of unstable carotid plaques in men was significantly higher than in women (OR = 1.562, p = 0.040). The probability of age-associated quartiles related to the first quartile demonstrated significant increase in plaque instability in the group of 65- to 69-year-old patients (OR 1.867, p = 0.024) and for patients older than 74 years (OR 1.740, p = 0.040). Conclusions: Asymptomatic men had in total more frequently unstable plaques in contrast to women. Thus, male sex seems to be an additional risk factor for ischemic stroke.


2015 ◽  
Vol 8s1 ◽  
pp. MRI.S23560 ◽  
Author(s):  
Gerald S. Treiman ◽  
J. Scott McNally ◽  
Seong-Eun Kim ◽  
Dennis L. Parker

Carotid therosclerotic disease causes approximately 25% of the nearly 690,000 ischemic strokes each year in the United States. Current risk stratification based on percent stenosis does not provide specific information on the actual risk of stroke for most individuals. Prospective randomized studies have found only 10 to 12% of asymptomatic patients will have a symptomatic stroke within 5 years. Measurements of percent stenosis do not determine plaque stability or composition. Reports have concluded that cerebral ischemic events associated with carotid plaque are intimately associated with plaque instability. Analysis of retrospective studies has found that plaque composition is important in risk stratification. Only MRI has the ability to identify and measure the detailed components and morphology of carotid plaque and provides more detailed information than other currently available techniques. MRI can accurately detect carotid hemorrhage, and MRI identified carotid hemorrhage correlates with acute stroke.


2021 ◽  
Author(s):  
Francesca Servadei ◽  
Lucia Anemona ◽  
Marina Cardellini ◽  
Manuel Scimeca ◽  
Manuela Montanaro ◽  
...  

Abstract Background: Metabolic syndrome certainly favors growth of carotid plaque; however, it is uncertain if it determines plaque destabilization. Furthermore, it is likely that only some components of metabolic syndrome are associated with increased risk of plaque destabilization. Therefore, we evaluated the effect of different elements of metabolic syndrome, individually and in association, on carotid plaques destabilization. Methods: A total of 186 carotid endarterectomies from symptomatic and asymptomatic patients were histologically analysed and correlated with major cardiovascular risk factors. Results: Metabolic syndrome, regardless of the cluster of its components, is not associated with a significant increase in risk of plaque destabilization, rather with the presence of stable plaques. The incidence of unstable plaques in patients with metabolic syndrome is quite low (43.9%), when compared with that seen in the presence of some risk factors, but significantly increases in the subgroup of female patients with hypertriglyceridemia, showing an odds ratio of 3.01 (CI 95% 0.25 - 36.30). Conclusions: Our data may help to identify patients with real increased risk of acute cerebrovascular diseases and may support the hypothesis that the control of hypertriglyceridemia should be a key point on prevention of carotid atherosclerotic plaque destabilization, especially in post-menopausal female patients. Keywords: Metabolic syndrome, carotid, histology, hypertriglyceridemia , post-menopause.


Stroke ◽  
2021 ◽  
Author(s):  
Russell Yanofsky ◽  
Carina Sancho ◽  
Karina Gasbarrino ◽  
Huaien Zheng ◽  
Robert J. Doonan ◽  
...  

Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques ( P <0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques ( P <0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability ( P <0.05). No strong sex-specific relationship was observed between adipokines and plaque instability. Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.


Angiology ◽  
2020 ◽  
pp. 000331972096541
Author(s):  
Alicia Bueno ◽  
Jose Ramon March ◽  
Pilar Garcia ◽  
Cristina Cañibano ◽  
Antonio Ferruelo ◽  
...  

Carotid plaque inflammation assessed by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are higher in symptomatic patients. The aim of this study was to assess correlations between 18F-FDG uptake on PET scan of carotid artery plaques, plasma levels of Lp-PLA2, and cerebrovascular symptoms. The study included 45 consecutive patients (22 symptomatic, 23 asymptomatic) with >70% carotid stenosis. Patients were examined by hybrid PET/CT, and maximum standardized uptake values (SUVmax) were recorded. Blood samples were obtained, and plasma was stored at −80 °C for subsequent Lp-PLA2 analysis. Symptomatic and asymptomatic patients showed no significant difference in classical cardiovascular risk factors. Asymptomatic carotid stenosis patients more frequently had a history of coronary artery disease ( P = .025) and peripheral artery disease ( P = .012). The symptomatic group had higher 18F-FDG uptake in carotid plaques ( P < .001), higher plasma Lp-PLA2 ( P < .01), and higher high-sensitive C-reactive protein ( P = .022). 2-Deoxy-2-[18F]fluoro-D-glucose uptake on PET/CT and plasma Lp-PLA2 show a statistically significant association with the symptomatic status of carotid plaques.


Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2117
Author(s):  
Manuel Scimeca ◽  
Manuela Montanaro ◽  
Marina Cardellini ◽  
Rita Bonfiglio ◽  
Lucia Anemona ◽  
...  

Background: The aim of this study was to evaluate how the high sensitivity C-reactive protein (hs-CRP) values influence the risk of carotid plaque instability in association with other cardiovascular risk factors. Methods: One hundred and fifty-six carotid plaques from both symptomatic and asymptomatic patients requiring surgical carotid endarterectomy were retrospectively collected. According to the modified American Heart Association, atherosclerosis plaques have been histologically distinguished into unstable and stable. The following anamnestic and hematochemical data were also considered: age, gender, hypertension, diabetes mellitus, smoking habit, therapy, low-density lipoprotein (LDL)-C, kidney failure and hs-CRP. Results: The results of our study clearly show that high levels of hs-CRP significantly increase the carotid plaque instability in dyslipidemic patients. Specifically, a 67% increase of the risk of carotid plaque instability was observed in patients with high LDL-C. Therefore, the highest risk was observed in male dyslipidemic patients 2333 (95% CI 0.73–7.48) and in aged female patients 2713 (95% CI 0.14–53.27). Discussion: These data strongly suggest a biological relationship between the hs-CRP values and the alteration of lipidic metabolism mostly in male patients affected by carotid atherosclerosis. The measurement of hs-CRP might be useful as a potential screening tool in the prevention of atheroscletotic disease.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 856-856
Author(s):  
Raegan Durant ◽  
Emily Levitan ◽  
Paul Muntner ◽  
Todd Brown ◽  
Monika M Safford

Abstract The REGARDS-MI ancillary study provided new outcomes of heart disease events and adjudicated cause of death. A primary focus has been disparities in and risk factors for coronary artery disease. We demonstrated that compared to White men, Black men have a higher risk of fatal coronary heart disease (CHD) but a lower risk of non-fatal CHD. Ongoing work is investigating potential reasons for this. We have investigated the role of CHD in aging including the relationship between heart failure and cognitive function and the association of MI with functional status. The REGARDS-MI study has served as a platform for mentoring trainees and early stage investigators, many from underrepresented groups, and provided data to a large number of investigators to purse research in CHD. To date, REGARDS-MI has contributed to nearly 200 publications and spawned additional ancillary studies. This presentation will highlight some of these publications and other research in progress.


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