Abstract 481: Disturbed Flow Arterial Intimal Hyperplasia Model in the Mouse Carotid Artery Induced by a Focal Stenosis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Christine R Mauro ◽  
Ming Tao ◽  
Binh Nguyen ◽  
Peng Yu ◽  
C K Ozaki
Keyword(s):  
Carotid Artery ◽  
Intimal Hyperplasia ◽  
Outer Diameter ◽  
High Grade ◽  
Murine Models ◽  
Molecular Dissection ◽  
Disturbed Flow ◽  
Diet Induced Obesity ◽  
Normal Chow ◽  
Focal Stenosis

Objective: Murine models offer a power tool for the molecular dissection of remodeling and intimal hyperplasia mechanisms, though technical challenges limit their utility. While simple, complete carotid ligation lacks direct clinical relevance, and branch outflow ligations require advanced microsurgical skills. We thus developed a simple and clinically relevant mouse model based on the hypothesis that locally disturbed flow caused by a focal high grade stenosis would yield arterial intimal hyperplasia thickening, and that the standardized diet induced obesity (DIO) model would accentuate this response. Methods: A focal stenosis in 8 week old C57BL/6J mice (normal chow (NC, 10 kcal% fat) or DIO chow (60 kcal% fat) throughout study) was created by placing 9-0 nylon suture around the distal common carotid artery and an external 35-gauge needle (outer diameter=0.14mm), and then removing the needle to restore blood flow (∼78% reduction of lumen diameter; n=20). Tissues were perfusion fixed for morphology 4 weeks later. Results: Both NC and DIO groups developed intimal hyperplasia proximal to the stenosis, with approximately three-times more in the DIO animals (Figure 1). Conclusions: In the mouse, a surgically created focal stenosis yields an intimal hyperplastic wall response. DIO accentuates this response. This model offers a tool for investigating mechanisms of hemodynamically driven mechanisms governing intimal hyperplasia formation.

Abstract 270: Acute Reductions in Wall Strain Precede Formation of Intimal Hyperplasia

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
John T Favreau ◽  
Chengwei Liu ◽  
Peng Yu ◽  
Christine Mauro ◽  
Ming Tao ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Murine Model ◽  
Intimal Hyperplasia ◽  
Arterial Wall ◽  
Lumen Area ◽  
Subsequent Removal ◽  
Distal Mouse ◽  
Intimal Thickness ◽  
Acute Changes ◽  
Focal Stenosis

Intimal hyperplasia (IH) remains the major culprit in revascularization failures. We aimed to unravel relationships between acute changes in circumferential arterial wall strain and genesis of IH. Methods To induce IH, we employed a validated model using a 9-0 nylon suture tie around the distal mouse common carotid artery (n=10) and an external 35-gauge needle mandrel (OD=0.14mm), with subsequent removal of the mandrel to create a distal common carotid focal stenosis (~78% lumen diameter/~85% flow reduction). Wall strains were measured in three, 1 mm wide regions along the vessel proximal to the focal stenosis at pre-op day 1 and at post-op day 4 (before detectable IH) using Vevo 2100 ultrasonography with VevoVasc software. At post-op day 28, arteries were perfusion fixed and IH was assessed in the same regions as those where strain was analyzed. Strain and morphology were also assessed in the contralateral control artery. Results Decreased wall strain was noted in all regions proximal to the focal stenosis from 0.26 ± 0.01 to 0.11 ± 0.02 (p<0.001) with no change in the control artery from pre-op to post-op day 4 (p=0.45). Based on a strain level histogram, vessels were divided into groups with strain ≤0.1 and >0.1. All segments (n = 13) with wall strain ≤0.1 at post-op day 4 had significant IH at day 28. In regions with strains >0.1 at day 4, only 30% had IH at day 28. The average pre-op strains were identical in >0.1 and ≤0.1 strain groups (0.27 ± 0.09 and 0.27 ± 0.08). Mean intimal thickness in vessels with strain ≤0.1 was 32 ± 20 μm, significantly greater than 8.0 ± 16 μm in the group with strain >0.1 (p<0.01). To further understand the mechanisms underlying changes in strain, systolic and diastolic lumen areas were assessed. Although systolic lumen areas in both >0.1 and ≤0.1 groups remained unchanged from pre-op to post-op day 4 (p=0.46), diastolic area was significantly increased in regions with post-op day 4 strain ≤0.1 (p=0.04) but remained unchanged in mice with post-op day 4 strain >0.1 (p=0.67). Conclusions Acute reduction in wall strain precedes the formation of IH in this murine model and this change is primarily caused by an increase in diastolic lumen area. Manipulations of wall strain offer a strategy to prevent and attenuate occlusive IH lesions after revascularizations.

Local Delivery of Vascular Endothelial Growth Factor Accelerates Reendothelialization and Attenuates Intimal Hyperplasia in Balloon-Injured Rat Carotid Artery

Circulation ◽  
1995 ◽  
Vol 91 (11) ◽  
pp. 2793-2801 ◽  
Author(s):  
Takayuki Asahara ◽  
Christophe Bauters ◽  
Christopher Pastore ◽  
Marianne Kearney ◽  
Susan Rossow ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Carotid Artery ◽  
Intimal Hyperplasia ◽  
Local Delivery ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Association between Pre-Existing Coronary Artery Disease and 5-Year Mortality in Stroke Patients with High-Grade Carotid Artery Stenosis

2020 ◽  
pp. 1-7
Author(s):  
Ching-I Wu ◽  
Chia-Lun Wu ◽  
Feng-Chieh Su ◽  
Shun-Wen Lin ◽  
Wen-Yi Huang
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Significant Risk ◽  
Cox Proportional Hazards Model ◽  
Artery Stenosis ◽  
High Grade ◽  
Increased Risk ◽  
Artery Disease

<b><i>Background:</i></b> The coincidence of coronary artery disease (CAD) and carotid artery stenosis (CAS) was observed. However, the association between pre-existing CAD and ischemic stroke (IS) outcome in patients with high-grade CAS remains unclear. We aimed to investigate the association between pre-existing CAD and outcomes of acute IS patients with high-grade CAS. <b><i>Methods:</i></b> From January 1, 2007, to April 30, 2012, we enrolled 372 acute IS patients with high-grade CAS and prospectively observed them for 5 years. Demographic features, vascular risk factors, comorbidities, and outcomes were compared between patients with and without pre-existing CAD. <b><i>Results:</i></b> Among 372 individuals, 75 (20.2%) patients had pre-existing CAD and 297 (79.8%) patients did not have pre-existing CAD. The prevalence rates of hypertension, congestive heart failure, chronic kidney disease, and gout in patients with pre-existing CAD were significantly higher than in those without pre-existing CAD (<i>p</i> = 0.017, <i>p</i> &#x3c; 0.001, <i>p</i> = 0.002, and <i>p</i> &#x3c; 0.001, respectively). The multivariate Cox proportional hazards model revealed that pre-existing CAD was a significant risk factor for a 5-year all-cause mortality in acute IS patients with high-grade CAS (hazard ratio = 2.26; 95% confidence interval = 1.35–3.79; <i>p</i> = 0.002). <b><i>Conclusion:</i></b> Pre-existing CAD was associated with an increased risk of 5-year mortality in acute IS patients with high-grade CAS. Intensive treatment for the pre-existing CAD may reduce long-term mortality in acute IS patients with high-grade CAS.

scholarly journals Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. e66-e73 ◽  
Author(s):  
Chih-Wen Ni ◽  
Haiwei Qiu ◽  
Amir Rezvan ◽  
Kihwan Kwon ◽  
Douglas Nam ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Ex Vivo ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Gene Expression Profiles ◽  
Disturbed Flow ◽  
A Genome ◽  
Pattern Comparison

Abstract Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.

scholarly journals Diagnostic dilemmas of multislice CT angiography in the evaluation of the degree of common carotid artery stenosis

2010 ◽  
Vol 138 (7-8) ◽  
pp. 494-497
Author(s):  
Dragoslav Nenezic ◽  
Slobodan Tanaskovic ◽  
Predrag Gajin ◽  
Nenad Ilijevski ◽  
Goran Vucurevic
Keyword(s):  
Carotid Artery ◽  
Ct Angiography ◽  
Common Carotid Artery ◽  
Carotid Artery Stenosis ◽  
Soft Tissues ◽  
Multislice Ct ◽  
Diagnostic Procedures ◽  
Left Common Carotid Artery ◽  
Artery Stenosis ◽  
High Grade

Introduction. Multislice CT angiography (CTA) is a noninvasive and quick technique to image carotid artery stenosis, as well as intracerebral vasculature. Modern multidetector CTA produces images with a high resolution of, not only the contrast-filled lumen, but also of the vessel wall and the surrounding soft tissues. Multiple studies have verified the ability of CTA to provide an accurate representation of the degree of carotid stenosis in comparison to digital subtraction angiography, both for moderate and high-grade stenosis. Because of its fast and accurate vessel imaging, CT angiography is increasingly used in the assessment of carotid artery stenosis. Case Outline. A 37-year-old female patient was admitted at the Vascular Surgery Clinic of the Institute for Cardiovascular Diseases 'Dedinje', Belgrade, for angiography and endovascular procedure of a high-grade stenosis of the left common carotid artery based on Multislice CT findings brought by the patient. She complained of problems which we considered to be the result of cerebral circulation ischemia. After detailed diagnostic procedures, we concluded that no pathological lesions could be verified either on the left common carotid artery or other supraaortic branches. Therefore, the patient was discharged for further neurological examinations. Conclusion. Although Multislice CTA has many advantages over classical angiography, its validity should be taken with reserve, especially in younger patients.

Contralateral High-Grade Carotid Artery Stenosis or Occlusion Is Not Associated with Increased Risk for Poor Neurologic Outcome after Elective Carotid Stent Placement

Radiology ◽  
2004 ◽  
Vol 230 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Schila Sabeti ◽  
Martin Schillinger ◽  
Wolfgang Mlekusch ◽  
Tassilo Nachtmann ◽  
Wilfried Lang ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Stent Placement ◽  
Carotid Artery Stenosis ◽  
Artery Stenosis ◽  
Neurologic Outcome ◽  
High Grade ◽  
Carotid Stent ◽  
Increased Risk

Abstract WP162: Impact of Carotid Artery Remodeling by T1 weighted MR Imaging for the Assessment of Plaque Vulnerability in High-grade Carotid Stenosis

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Kenji Fukuda ◽  
Koji Iihara ◽  
Naoaki Yamada ◽  
Hatsue Ueda
Keyword(s):  
Carotid Artery ◽  
Carotid Stenosis ◽  
Average Rate ◽  
Intraplaque Hemorrhage ◽  
High Grade ◽  
Plaque Vulnerability ◽  
Rapid Acquisition ◽  
Asymptomatic Patients ◽  
Artery Remodeling ◽  
The Relationship

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.

Sign in / Sign up

Export Citation Format

Share Document