Neovascularization and Angiogenic Factors in Advanced Human Carotid Artery Stenosis

Pelisek, Jaroslav; Well, Georg; Reeps, Christian; Rudelius, Martina; Kuehnl, Andreas; Culmes, Mihaela; Poppert, Holger; Zimmermann, Alexander; Berger, Hermann; Eckstein, H.‐H.

doi:10.1253/circj.cj-11-0768

Cited by 52 publications

(39 citation statements)

References 31 publications

(24 reference statements)

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“…In line with this notion, we recently demonstrated that in subjects with type 2 diabetes mellitus, symptomatic patients have lower plaque levels of PDGF and collagen than asymptomatic patients. 29 In contrast, Pelisek et al 30 analyzed the amount of PDGF in advanced human carotid artery stenosis and found no significant difference in PDGF levels between symptomatic and asymptomatic plaques.…”

Section: Discussionmentioning

confidence: 97%

High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events

Rattik

Wigren

Björkbacka

et al. 2015

ATVB

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Objective-Rupture of atherosclerotic plaques is the major cause of acute coronary events (CEs). Plaque destabilization is the consequence of an imbalance between inflammatory-driven degradation of fibrous tissue and smooth muscle celldependent tissue repair. Proinflammatory factors have been documented extensively as biomarkers of cardiovascular risk but factors that contribute to stabilization of atherosclerotic plaques have received less attention. The present study aimed to investigate whether plasma levels of the smooth muscle cell growth factor epidermal growth factor (EGF), heparinbinding-EGF (HB-EGF), and platelet-derived growth factor correlate with plaque phenotype and incidence of CEs. Approach and Results-HB-EGF, EGF and platelet-derived growth factor were measured in plasma from 202 patients undergoing carotid endarterectomy and in 384 incident CE cases and 409 matched controls recruited from the Malmö Diet and Cancer cohort. Significant positive associations were found between the plasma levels of all 3 growth factors and the collagen and elastin contents of the removed plaques. CE cases in the Malmö Diet and Cancer cohort had lower levels of HB-EGF in plasma, whereas no significant differences were found for EGF and platelet-derived growth factor. After adjusting for cardiovascular risk factors in a Cox proportional hazard model, the hazard ratio for the highest HB-EGF tertile was 0.61 (95% confidence interval, 0.47-0.82; P<0.001). Conclusions-The associations between high levels of smooth muscle cell growth factors in plasma and a more fibrous plaque phenotype as well as the association between low levels of HB-EGF and incident CEs point to a potential clinically important role for factors that contribute to plaque stabilization by stimulating smooth muscle cells.

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Section: Discussionmentioning

confidence: 97%

High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events

Rattik

Wigren

Björkbacka

et al. 2015

ATVB

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“…Histological characterization of atherosclerotic plaques was performed following the hematoxylin-eosin and elastic van Gieson staining procedures to assess the pathomorphological features of all segments, as described previously [5,20,22]. Lesion stability was defi ned as described by Redgrave et al [23], considering a thin fi brous cap of less than 200 μm over a large lipid-rich atheroma as a cut-off to distinguish between stable and unstable atherosclerotic plaques ( Figure 1).…”

Section: Histological Analysis Of Atherosclerotic Plaquesmentioning

confidence: 99%

Impact of sex and age on carotid plaque instability in asymptomatic patients-results from the Munich Vascular Biobank

Wendorff

Kuehnl

et al. 2016

Vasa

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IntroductionStroke is one of the leading causes of death and disability in western societies and a prevalent public health concern worldwide [1]. Extracranial carotid artery stenosis due to atherosclerotic plaque burden is one of the major risk factors of forthcoming stroke [2]. Epidemiologic data document that ischemic stroke attributable to a diseased carotid artery corresponds with up to 18 % of all incidents leading to neurological events [3,4]. Furthermore, the prevalence of a cervical internal carotid artery stenosis increases with age and can be found in 6.9 % of the elderly population (> 65 years) [5]. Large randomized clinical trials (the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST)) have provided clear evidence of the usefulness of surgical treatment of patients with neurological symptoms for a degree of stenosis > 50 % in NAS-CET and > 70 % in ECST [6,7]. In contrast, the benefi t of carotid endarterectomy (CEA) for asymptomatic patients is less clear. Large multicenter randomized studies for asymptomatic carotid artery disease (the Asymptomatic Carotid Surgery Trial (ACST) and the Asymptomatic Carotid Atherosclerosis Study (ACAS)) demonstrated a small reduction in secondary stroke risk using CEA compared to medical treatment [8,9]. However, the absolute risk reduction was rather small [10,11].Epidemiological studies have already revealed that aging and sex are independent risk factors for cardiovascular disease [12,13]. However, the question as to how far potential changes in carotid plaque morphology might contribute to ischemic stroke during aging, especially due to unstable atherosclerotic lesions, has not yet been elucidated. Interestingly, very few studies have focused so far on lesion morphology and instability as a function of age, sex, or patient symptomatology [14 -20]. The data suggest that especially neurological symptoms are often caused by critical changes in carotid plaque morphology, leading to lesion instability. Consequently, unfavorable alterations in the pathophysiology of atherosclerotic plaques in asymptomatic patients might cause an increased risk of stroke.The aim of the current study was therefore to analyze plaque instability as a function of age and sex in patients with asymptomatic carotid artery stenosis by means of his- 2004 -2013) at the Munich Vascular Biobank were analyzed. Ascertainment of lesion stability/instability was performed on formalin-fi xed paraffi n-embedded tissue samples using hematoxylin-eosin and elastic van Gieson staining. Unstable plaques were considered lesions with a fi brous 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 ...

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“…Namely, increased neovascularization is considered an important contributing factor for atherosclerotic plaque progression and vulnerability [5] and may explain the increased risk of atherosclerotic complications in subjects with T2DM [6,7]. Significant correlations were observed between neovascularization, plaque stability, and expression of angiogenic factors, especially vascular endothelial growth factor A (VEGF) [8].…”

Section: Introductionmentioning

confidence: 99%

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

Kariž

Petrovič

2014

Clinical Biochemistry

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Neovascularization and Angiogenic Factors in Advanced Human Carotid Artery Stenosis

Cited by 52 publications

References 31 publications

High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events

High Plasma Levels of Heparin-Binding Epidermal Growth Factor Are Associated With a More Stable Plaque Phenotype and Reduced Incidence of Coronary Events

Impact of sex and age on carotid plaque instability in asymptomatic patients-results from the Munich Vascular Biobank

Minor association of kinase insert domain-containing receptor gene polymorphism (rs2071559) with myocardial infarction in Caucasians with type 2 diabetes mellitus: Case–control cross-sectional study

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