scholarly journals Possible involvement of pericytes in intraplaque hemorrhage of carotid artery stenosis

2019 ◽  
Vol 130 (6) ◽  
pp. 1971-1977 ◽  
Author(s):  
Tatsuya Tanaka ◽  
Atsushi Ogata ◽  
Jun Masuoka ◽  
Taichiro Mizokami ◽  
Tomihiro Wakamiya ◽  
...  

OBJECTIVEIntraplaque hemorrhage (IPH) is most often caused by the rupture of neovessels; however, the factors of intraplaque neovessel vulnerability remain unclear. In this study, the authors focused on pericytes and aimed to investigate the relationship between IPH and pericytes.METHODSThe authors retrospectively analyzed the medical records of all patients with carotid artery stenoses who had undergone carotid endarterectomy at their hospitals between August 2008 and March 2016. Patients with carotid plaques that could be evaluated histopathologically were eligible for study inclusion. Intraplaque hemorrhage was analyzed using glycophorin A staining, and patients were divided into the following 2 groups based on the extent of granular staining: high IPH (positive staining area > 10%) and low IPH (positive staining area ≤ 10%). In addition, intraplaque neovessels were immunohistochemically evaluated using antibodies to CD34 as an endothelial cell marker or antibodies to NG2 and CD146 as pericyte markers. The relationship between IPH and pathology for intraplaque neovessels was investigated.RESULTSSeventy of 126 consecutive carotid stenoses were excluded due to the lack of a specimen for histopathological evaluation; therefore, 53 patients with 56 carotid artery stenoses were eligible for study inclusion. Among the 56 stenoses, 37 lesions had high IPH and 19 had low IPH. The number of CD34-positive neovessels was equivalent between the two groups. However, the densities of NG2- and CD146-positive neovessels were significantly lower in the high IPH group than in the low IPH group (5.7 ± 0.5 vs. 17.1 ± 2.4, p < 0.0001; 6.6 ± 0.8 vs. 18.4 ± 2.5, p < 0.0001, respectively).CONCLUSIONSPlaques with high IPH are associated with fewer pericytes in the intraplaque neovessels. This finding may help in the development of novel therapeutic strategies targeting pericytes.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kenji Fukuda ◽  
Koji Iihara ◽  
Naoaki Yamada ◽  
Hatsue Ueda

Background- The relationship between coronary artery remodeling and plaque vulnerability has been described on the basis of symptomatology and histology. However, the association with carotid artery remodeling has not been explored in detail. The aim of this study was to validate the relationship between carotid artery remodeling and plaque vulnerability by comparing the degree of outward remodeling calculated using 3D inversion-recovery-based T1-weighted imaging (magnetization-prepared rapid acquisition gradient-echo [MPRAGE]) with the symptomatology and histology of plaques extracted during carotid endarterectomy (CEA). Methods and Results- Sixty-one patients with high-grade carotid stenosis who underwent CEA and whose plaque could be examined were included. The average rate of stenosis as per the NASCET criteria was 79.8%. The carotid remodeling index (CRI) was determined by measuring the external cross-sectional vessel area (CSVA) of the maximum stenosis of the internal carotid artery (ICA) and dividing it by the external CSVA of the distal ICA unaffected by atherosclerosis using MPRAGE imaging. The relationship between the CRI and plaque vulnerability was evaluated on the basis of symptomatology and histology. The CRI was significantly higher in symptomatic patients than in asymptomatic patients (1.98 ± 0.26 vs. 1.68 ± 0.24, p < 0.0001). A higher CRI was positively correlated with the necrotic core area (r = 0.568, p < 0.0001) as well as significantly associated with severe intraplaque hemorrhage (p < 0.0001) and the prevalence of cap inflammation with macrophage (p = 0.03) and lymphocyte (p = 0.01) infiltration. Conclusion- These results validate the relationship between carotid artery remodeling and plaque vulnerability in high-grade carotid stenosis. MPRAGE imaging is effective to assess plaque vulnerability in terms of the CRI in addition to the signal intensity of carotid plaques.


2016 ◽  
Vol 126 (6) ◽  
pp. 1873-1878 ◽  
Author(s):  
Atsushi Ogata ◽  
Masatou Kawashima ◽  
Tomihiro Wakamiya ◽  
Masashi Nishihara ◽  
Jun Masuoka ◽  
...  

OBJECTIVEHypoxia induces angiogenesis and plays a major role in the progression of carotid plaques. During carotid intervention, plaques with high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) often cause ischemic stroke and embolic complications. However, the role of intraplaque hypoxia before carotid endarterectomy (CEA) and carotid artery stenting is not presently understood. In this study the authors aimed to investigate the relationship between intraplaque hypoxia and MRA findings.METHODSNineteen consecutive patients with 20 carotid artery stenoses who underwent CEA at Saga University Hospital between August 2008 and December 2014 were enrolled in the study. The expressions of hypoxia-inducible transcription factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemical analysis. In addition, the relationship between the findings on TOF MRA and pathology for the carotid plaques was analyzed.RESULTSHigh-intensity plaques on TOF MRA showed higher expression levels of HIF-1α (p = 0.015) and VEGF (p = 0.007) compared with isointensity plaques. The rate of intraplaque hemorrhage (IPH) on TOF MRA was also significantly higher in the high-intensity plaques than in the isointensity plaques (p = 0.024). Finally, the mean number of neovessels was significantly higher in those without plaque hemorrhage than in those with plaque hemorrhage (p = 0.010).CONCLUSIONSPlaques with high-intensity signals on TOF MRA were associated with IPH and evidence of intraplaque hypoxia. This fact may represent an opportunity to establish novel therapeutic agents targeting intraplaque hypoxia.


2015 ◽  
Vol 39 (5-6) ◽  
pp. 319-324 ◽  
Author(s):  
Quirijn J.A. van den Bouwhuijsen ◽  
Daniel Bos ◽  
M. Arfan Ikram ◽  
Albert Hofman ◽  
Gabriel P. Krestin ◽  
...  

Background: There is a growing amount of evidence suggesting that the composition of carotid atherosclerotic plaques may be of clinical relevance. Yet, little is known on the coexistence of potentially vulnerable and stabilizing components within asymptomatic plaques. Therefore, in this study we set out to investigate the coexistence of intraplaque calcification, hemorrhage and lipid core within the carotid artery using a multi-modality imaging approach. Methods: In 329 subjects from the population-based Rotterdam Study, all with ultrasound-confirmed carotid wall thickening, we performed a multi-detector CT and a high-resolution MRI of the carotid artery bifurcation at both sides. On the CT examinations, we quantified the volume of intraplaque calcification, and using the MRI examinations we rated the presence of intraplaque hemorrhage and of lipid core. In total, we investigated 611 carotid arteries with plaques. With logistic regression models we investigated the relationship of calcification volume - as a potential stabilizing component - with the presence of potential vulnerable components (intraplaque hemorrhage and lipid core) within each carotid plaque. We adjusted all analyses for age, sex and maximal plaque thickness. Next, we stratified on degree of stenosis (≤ or >30%) to evaluate effect modification by atherosclerotic burden. Results: We found that a larger calcification volume was associated with a higher prevalence of intraplaque hemorrhage, and a lower prevalence of lipid core (fully-adjusted odds ratio (OR) per standard deviation (SD) increase in calcification volume: 2.04 (95% confidence intervals (CI): 1.49; 2.78) and 0.72 (95% CI: 0.58; 0.90), respectively). Stratification on the degree of stenosis showed no difference in the association between calcification volume and hemorrhage over strata, while the relationship between a larger calcification volume and a lower prevalence of lipid seemed more pronounced in persons with a high degree of stenosis. Conclusions: In this population-based setting, we found that there is a complex relationship between calcification, intraplaque hemorrhage and lipid core within the carotid atherosclerotic plaque. Plaques with a higher load of calcification contain more often hemorrhagic components, but less often lipid core. Our results suggest that both in small and large plaques, intraplaque calcification may not be a stabilizing factor per se. These findings create an urge for conducting prospective studies investigating the interrelation of these different plaque components with regard to future cerebrovascular events.


TH Open ◽  
2021 ◽  
Vol 05 (02) ◽  
pp. e113-e124
Author(s):  
Elsa Wilma Böhm ◽  
Maria Pavlaki ◽  
Georgios Chalikias ◽  
Dimitrios Mikroulis ◽  
George S. Georgiadis ◽  
...  

Abstract Background Intimal calcification typically develops in advanced atherosclerosis, and microcalcification may promote plaque progression and instability. Conversely, intraplaque hemorrhage and erythrocyte extravasation may stimulate osteoblastic differentiation and intralesional calcium phosphate deposition. The presence of erythrocytes and their main cellular components (membranes, hemoglobin, and iron) and colocalization with calcification has never been systematically studied. Methods and Results We examined three types of diseased vascular tissue specimens, namely, degenerative aortic valve stenosis (n = 46), atherosclerotic carotid artery plaques (n = 9), and abdominal aortic aneurysms (n = 14). Biomaterial was obtained from symptomatic patients undergoing elective aortic valve replacement, carotid artery endatherectomy, or aortic aneurysm repair, respectively. Serial sections were stained using Masson–Goldner trichrome, Alizarin red S, and Perl's iron stain to visualize erythrocytes, extracelluar matrix and osteoid, calcium phosphate deposition, or the presence of iron and hemosiderin, respectively. Immunohistochemistry was employed to detect erythrocyte membranes (CD235a), hemoglobin or the hemoglobin scavenger receptor (CD163), endothelial cells (CD31), myofibroblasts (SMA), mesenchymal cells (osteopontin), or osteoblasts (periostin). Our analyses revealed a varying degree of intraplaque hemorrhage and that the majority of extravasated erythrocytes were lysed. Osteoid and calcifications also were frequently present, and erythrocyte membranes were significantly more prevalent in areas with calcification. Areas with extravasated erythrocytes frequently contained CD163-positive cells, although calcification also occurred in areas without CD163 immunosignals. Conclusion Our findings underline the presence of extravasated erythrocytes and their membranes in different types of vascular lesions, and their association with areas of calcification suggests an active role of erythrocytes in vascular disease processes.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Zhong-Song Shi ◽  
Xiao-Bing Jiang ◽  
Jin-Shan Wang ◽  
Wei-Si Yuan ◽  
Dong-Hong Liu

Purpose: The limited number of large animal carotid atherosclerotic models restricts the preclinical evaluation of endovascular therapies. Carotid intraplaque hemorrhage may be associated with a higher risk of ischemic stroke in patients with carotid disease. In this study, we assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with vulnerable atherosclerotic carotid plaque and intraplaque hemorrhage in a Swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for MMP-9 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. Atherosclerotic changes were classified by AHA/Stary stage (type I to VI). The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of MMP-9 expression in the plaque with the vulnerable plaque and intraplaque hemorrhage was further analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 segments had vulnerable plaque (Stary IV to VI). Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal ( P <0.0001). Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for MMP-9 tended to be greater in the vulnerable plaque than in the stable plaque (8.69 ± 0.73% vs. 7.04 ± 0.94%, p=0.35). Areas positive for MMP-9 were significantly greater in the plaque with intraplaque hemorrhage than in the plaque without intraplaque hemorrhage (11.84 ± 1.22% vs. 6.63 ± 0.59%, p<0.001). On multivariate analysis, positive expression of MMP-9 was an independent predictor of intraplaque hemorrhage (p=0.007). Conclusion: Vulnerable carotid plaques with distal embolism were created in a Swine model of carotid atherosclerosis. Increased expression of MMP-9 may be associated with vulnerable carotid plaques, especially having the feature of intraplaque hemorrhage.


2016 ◽  
Vol 24 (0) ◽  
Author(s):  
Daniele Natália Pacharone Bertolini Bidinotto ◽  
Janete Pessuto Simonetti ◽  
Silvia Cristina Mangini Bocchi

ABSTRACT Objectives: to evaluate the relationship between absences in scheduled appointments and the number of non-communicable chronic diseases and to investigate the relationship between spatial distribution of these diseases and social vulnerability, using geoprocessing. Method: a quantitative study of sequential mixed approach by analyzing 158 medical records of male users to relate the absences and 1250 medical records for geoprocessing Results: the higher the number of absences in the scheduled medical appointments, the less were the number of non-communicable chronic diseases and the ones listed in the International Classification of Diseases in single men. There were 21 significant geostatistically cases of glucose intolerance in the urban area. Of these, 62% lived in a region with a social vulnerability rating of Very Low, Medium 19%, 14% Low and 5% High. Conclusion: it was observed that the older the men, the greater is the number of chronic diseases and the less they miss scheduled appointments. Regarding the use of geoprocessing, we obtained a significant number of cases of glucose intolerance in urban areas, the majority classified as Very Low social vulnerability. It was possible to relate the spatial distribution of these diseases with the social vulnerability classification; however, it was not possible to perceive a relationship of them with the higher rates of social vulnerability.


2017 ◽  
Vol 24 (2) ◽  
Author(s):  
Wisnu Laksmana ◽  
Johan Renaldo ◽  
Tarmono Djojodimedjo

Objective: Determine the relationship between clinical symptoms of colic pain and haematuria as a predictor of ureteral stones incident at Dr Soetomo Hospital within a period of five years. Material & methods: This study is a descriptive analytic study using the sensitivity-specificity test with retrospective design. Data were collected from patient's medical records with a ureteral stone diagnosis at outpatient unit Dr Soetomo Hospital within 2011-2015. Results: Renal colic or ureter colic without haematuria had 88.32% specificity and 53.07% sensitivity in the incidence of ureteral stones at Urology Outpatient Unit Dr Soetomo Hospital within 2011-2015 period. Haematuria without colic complaint had 29.37% sensitivity and 90.17% specificity in the incidence of ureteral stones. Colic and haematuria compared with colic had 55.76% sensitivity for the incidence of ureteral stones and 70.09% specificity. While colic and haematuria compared with haematuria had a sensitivity of 77.41% for the incidence of ureteral stones and 65.92% specificity. Colic and haematuria compared to other complaints has a 58.77% sensitivity for ureteral stones incidence and 94.66% specificity. Conclusion: Colic and haematuria are clinical predictors that have a better value than the complaints of colic without haematuria and haematuria without colic, in the ureteral stones incident at Urology Outpatient Unit Dr Soetomo Hospital within 2011-2015 period. This is consistent with the literature that mentions prominent complaint in the incidence of ureteral stones is their colic pain caused by the stone through the ureteral passage, and followed by haematuria for their mucosal surface injury.


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