Histological Features of Symptomatic Carotid Plaques in Patients with Impaired Glucose Tolerance and Diabetes (Oxford Plaque Study)

Redgrave, Jessica; Lovett, J K; Syed, Atyab; Rothwell, Peter M.

doi:10.1159/000136900

Cited by 32 publications

(33 citation statements)

References 64 publications

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“…1,13,24 However, these observations could not be confirmed in the more recent Oxford Plaque Study, which showed no difference in inflammatory cells between plaques from subjects with DM II and subjects with normal glucose tolerance. 25 In line with this study, we found no difference in inflammatory markers and macrophage staining between DM II and nondiabetic plaques in the present study. It is possible that these inconsistencies reflect differences in study design, cohorts, or analytic approach.…”

supporting

confidence: 90%

Impaired Fibrous Repair

Edsfeldt

Gonçalves

Grufman

et al. 2014

ATVB

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Collectively, these observations have hinted that atherosclerotic plaques from subjects with DM II are more prone to rupture because of increased inflammatory activity.However, the actual inflammatory activity in plaques has been less well investigated. Using a novel approach to analyze plaque inflammation, determining the total plaque content of chemokines, proinflammatory cytokines, growth factors, © 2014 American Heart Association, Inc. Objective-Diabetes mellitus (DM) type II is increasing rapidly worldwide. Patients with DM II have a greater atherosclerotic burden and higher risk of developing cardiovascular complications. Inflammation has been proposed as the main cause for the high risk of atherosclerotic disease in DM II. In this study, we compared markers of inflammation and fibrous repair in plaques from subjects with and without DM II. Approach and Results-Carotid endarterectomy specimens were obtained from 63 patients with and 131 without DM.Plaque structure, connective tissue proteins, inflammatory cells, and markers were analyzed by immunohistochemistry, ELISA, Mesoscale, and Luminex technology. Carotid plaques from diabetics had lower levels of extracellular matrix proteins, elastin, and collagen, which are critical for plaque stability. Plaques from diabetics had reduced levels of plateletderived growth factor and matrix metalloproteinase-2, both important for tissue repair. No differences were observed in inflammatory markers in plaques from diabetic and nondiabetic patients. Conclusion-This study suggests that atherosclerotic plaques in subjects with DM II are more prone to rupture because of impaired repair responses rather than to increased vascular inflammation. Although this study did not have a mechanistic design, our findings suggest that targeting impaired repair responses in carotid plaques may help to increase our understanding of atherosclerotic plaque development and vulnerability in patients with DM II. MMPs, tissue inhibitors of MMPs (TIMPs), collagen, and elastin, we demonstrate in this study that no significant difference in these inflammatory markers was to be found comparing plaques from subjects with and without DM II. Instead, plaques obtained from subjects with DM II showed markedly reduced levels of stabilizing extracellular matrix (ECM) proteins and growth factors, suggesting that the high risk for a plaque rupture may be attributed to an impaired tissue repair rather than an enhanced inflammatory activity. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Clinical Characteristics of the Study CohortSixty-three plaques were obtained from 63 subjects with DM II and 134 plaques were obtained from 131 subjects without DM. Subjects with DM II had higher body mass index and plasma triglycerides, whereas plasma low-density lipoprotein cholesterol levels were lower. Higher numbers of symptomatic plaques were observed in patients with DM II (Table 1). No significant difference (P=0.5) was found comparing patients with DM II (15, 54 [S...

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supporting

confidence: 90%

Impaired Fibrous Repair

Edsfeldt

Gonçalves

Grufman

et al. 2014

ATVB

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“…For this purpose, cerebral angiography, ultrasound, and 3D-CTA have been employed. However, recent studies have clarified that the morphology [30] and/or components of carotid plaque are alternative factors to determine the outcome in patients with carotid artery stenosis [10,11,31,32]. …”

Section: Discussionmentioning

confidence: 99%

Validity of Dual MRI and <sup>18</sup>F-FDG PET Imaging in Predicting Vulnerable and Inflamed Carotid Plaque

Saito

Kuroda

Hirata³

et al. 2013

Cerebrovasc Dis

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Background: Vulnerable and inflamed plaques in the carotid artery are at high risk of ischemic stroke, suggesting the importance of diagnostic modalities to detect them in patients with carotid stenosis with high sensitivity and specificity. Although many investigators have reported that magnetic resonance imaging (MRI) is a useful tool to predict the vulnerable components of carotid plaque, its validity is not established. On the other hand, ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) may be an alternative modality to directly identify the inflamed plaque in carotid artery stenosis. Therefore, this study aimed at evaluating the validity of MRI and FDG-PET to predict vulnerable and inflamed carotid plaque. Methods: This prospective study totally included 25 patients who underwent carotid endarterectomy (CEA) for carotid artery stenosis at our institute between January 2009 and January 2012. Prior to CEA, FDG-PET, black-blood T1-weighted imaging (BB-T1WI), and 3-dimensional time-of-flight (TOF) imaging were performed. The specimens were stained with hematoxylin-eosin to assess the different plaque components (lipid, hemorrhage, calcification, and fibrous tissue). In addition, they were stained with primary antibodies against CD68 (activated macrophages) and matrix metalloproteinase (MMP)-9. Results: High FDG uptake was detected in 13 (52.0%) of 25 patients. All of them had lipid-rich plaque. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to identify the lipid-rich plaques were all 100% for FDG-PET. More importantly, all of the FDG-positive plaques had strong immunoreactivity against both CD68 and MMP-9. There was a significant correlation between the findings on FDG-PET and those on immunohistochemistry against CD68 and MMP-9 (p = 0.006 and 0.004, respectively). On the other hand, 16 (64.0%) of 25 patients had high signal intensity plaque on BB-T1WI. In 7 of these 16 patients, the lesions also showed high signal intensity on TOF imaging. All of them had a large intraplaque hemorrhage. The sensitivity, specificity, PPV, and NPV to identify a large intraplaque hemorrhage were 70, 100, 100, and 83%, respectively, for MRI. Conclusions: These findings suggest that FDG-PET and MRI are complementary to predict high-risk carotid plaque, such as lipid-rich or hemorrhagic plaque. FDG-PET can accurately predict the lipid-rich and inflamed plaque. MRI is valuable to identify unstable plaque with a large intraplaque hemorrhage. The combination of these two modalities may play an important role in predicting carotid plaque at high risk of ischemic stroke.

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“…29 Similarly, CSE or components of CS were suggested to increase intraplaque inflammation and intraplaque neovascularization. [30][31][32][33] Intraplaque inflammation and intraplaque neovascularization lead to intraplaque hemorrhage and subsequent necrotic core enlargement. 26 Furthermore, CSE was found to cause an increased sympathetic activity leading to a rise in blood pressure, pulse rate, and vasospasm, which might create a high-mechanical stress zone near a vulnerable plaque.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

Barua

Ambrose

2013

ATVB

198

126

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Abstract-Acute rupture or erosion of a coronary atheromatous plaque and subsequent coronary artery thrombosis cause the majority of sudden cardiac deaths and myocardial infarctions. Cigarette smoking is a major risk factor for acute coronary thrombosis. Indeed, a majority of sudden cardiac deaths attributable to acute thrombosis are in cigarette smokers. Both active and passive cigarette smoke exposure seem to increase the risk of coronary thrombosis and myocardial infarctions. Cigarette smoke exposure seems to alter the hemostatic process via multiple mechanisms, which include alteration of the function of endothelial cells, platelets, fibrinogen, and coagulation factors. This creates an imbalance of antithrombotic/ prothrombotic factors and profibrinolytic/antifibrinolytic factors that support the initiation and propagation of thrombosis.

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Histological Features of Symptomatic Carotid Plaques in Patients with Impaired Glucose Tolerance and Diabetes (Oxford Plaque Study)

Cited by 32 publications

References 64 publications

Impaired Fibrous Repair

Impaired Fibrous Repair

Validity of Dual MRI and <sup>18</sup>F-FDG PET Imaging in Predicting Vulnerable and Inflamed Carotid Plaque

Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

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