Carotid Atherosclerotic Plaque Rupture Research Articles

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Association between plaque vulnerability and neutrophil extracellular traps (NETs) levels: The Plaque At RISK study

Carotid atherosclerotic plaque rupture and its sequelae are among the leading causes of acute ischemic stroke. The risk of rupture and subsequent thrombosis is, among others, determined by vulnerable plaque characteristics and linked to activation of the immune system, in which neutrophil extracellular traps (NETs) potentially play a role. The aim of this study was to investigate how plaque vulnerability is associated with NETs levels. We included 182 patients from the Plaque At RISK (PARISK) study in whom carotid imaging was performed to measure plaque ulceration, fibrous cap integrity, intraplaque hemorrhage, lipid-rich necrotic core, calcifications and plaque volume. Principal component analysis generated a 'vulnerability index' comprising all plaque characteristics. Levels of the NETs marker myeloperoxidase-DNA complex were measured in patient plasma. The association between the vulnerability index and low or high NETs levels (dependent variable) was assessed by logistic regression. No significant association between the vulnerability index and NETs levels was detected in the total population (odds ratio 1.28, 95% confidence interval 0.90-1.83, p = 0.18). However, in the subgroup of patients naive to statins or antithrombotic medication prior to the index event, this association was statistically significant (odds ratio 2.08, 95% confidence interval 1.04-4.17, p = 0.04). Further analyses revealed that this positive association was mainly driven by intraplaque hemorrhage, lipid-rich necrotic core and ulceration. In conclusion, plaque vulnerability is positively associated with plasma levels of NETs, but only in patients naive to statins or antithrombotic medication prior to the index event.

FOXC1 is a key transcription factor influencing smooth muscle cell activation in atherosclerotic plaques

Background and Aims: Rupture of carotid atherosclerotic plaques is a common cause for ischemic stroke. We aimed to characterize the major transcriptional regulators of molecules dysregulated in plaques from symptomatic vs. asymptomatic patients.

Analysis of MicroRNAs Associated With Carotid Atherosclerotic Plaque Rupture With Thrombosis.

Atherosclerosis is a progressive vascular wall inflammatory disease, and the rupture of atherosclerotic vulnerable plaques is the leading cause of morbidity and mortality worldwide. This study intended to explore the potential mechanisms behind plaque rupture and thrombosis in ApoE knockout mice. The spontaneous plaque rupture models were established, and left carotid artery tissues at different time points (1-, 2-, 4-, 6-, 8-, 12-, and 16-week post-surgery) were collected. By the extent of plaque rupture, plaque was defined as (1) control groups, (2) atherosclerotic plaque group, and (3) plaque rupture group. Macrophage (CD68), MMP-8, and MMP-13 activities were measured by immunofluorescence. Cytokines and inflammatory markers were measured by ELISA. The left carotid artery sample tissue was collected to evaluate the miRNAs expression level by miRNA-microarray. Bioinformatic analyses were conducted at three levels: (2) vs. (1), (3) vs. (2), and again in seven time series analysis. The plaque rupture with thrombus and intraplaque hemorrhage results peaked at 8 weeks and decreased thereafter. Similar trends were seen in the number of plaque macrophages and lipids, the expression of matrix metalloproteinase, and the atherosclerotic and plasma cytokine levels. MiRNA-microarray showed that miR-322-5p and miR-206-3p were specifically upregulated in the atherosclerotic plaque group compared with those in the control group. Meanwhile, miR-466h-5p was specifically upregulated in the plaque rupture group compared with the atherosclerotic plaque group. The highest incidence of plaque rupture and thrombosis occurred at 8 weeks post-surgery. miR-322-5p and miR-206-3p may be associated with the formation of atherosclerotic plaques. miR-466h-5p may promote atherosclerotic plaque rupture via apoptosis-related pathways.

BIRC6 Is Associated with Vulnerability of Carotid Atherosclerotic Plaque.

Carotid atherosclerotic plaque rupture can lead to cerebrovascular accident (CVA). By comparing RNA-Seq data from vascular smooth muscle cells (VSMC) extracted from carotid atheroma surgically excised from a group of asymptomatic and symptomatic subjects, we identified more than 700 genomic variants associated with symptomatology (p < 0.05). From these, twelve single nucleotide polymorphisms (SNPs) were selected for further validation. Comparing genotypes of a hospital-based cohort of asymptomatic with symptomatic patients, an exonic SNP in the BIRC6 (BRUCE/Apollon) gene, rs35286811, emerged as significantly associated with CVA symptomatology (p = 0.002; OR = 2.24). Moreover, BIRC6 mRNA levels were significantly higher in symptomatic than asymptomatic subjects upon measurement by qPCR in excised carotid atherosclerotic tissue (p < 0.0001), and significantly higher in carriers of the rs35286811 risk allele (p < 0.0001). rs35286811 is a proxy of a GWAS SNP reported to be associated with red cell distribution width (RDW); RDW was increased in symptomatic patients (p < 0.03), but was not influenced by the rs35286811 genotype in our cohort. BIRC6 is a negative regulator of both apoptosis and autophagy. This work introduces BIRC6 as a novel genetic risk factor for stroke, and identifies autophagy as a genetically regulated mechanism of carotid plaque vulnerability.

Studying the Factors of Human Carotid Atherosclerotic Plaque Rupture, by Calculating Stress/Strain in the Plaque, Based on CEUS Images: A Numerical Study.

Carotid plaque neovascularization is one of the major factors for the classification of vulnerable plaque, but the axial force effects of the pulsatile blood flow on the plaque with neovessel and intraplaque hemorrhage was unclear. Together with the severity of stenosis, the fibrous cap thickness, large lipid core, and the neovascularization followed by intraplaque hemorrhage (IPH) have been regarded as high-risk features of plaque rupture. In this work, the effects of these factors were evaluated on the progression and rupture of the carotid atherosclerotic plaques. Five geometries of carotid artery plaque were developed based on contrast-enhanced ultrasound (CEUS) images, which contain two types of neovessel and IPH, and geometry without neovessel and IPH. A one-way fluid-structure interaction model was applied to compute the maximum principal stress and strain in the plaque. For that hyper-elastic and non-linear material, Yeoh 3rd Order strain energy density function was used for components of the plaque. The simulation results indicated that the maximum principal stress of plaque in the carotid artery was higher when the degree of the luminal stenosis increased and the thickness of the fibrous cap decreased. The neovessels within the plaque could introduce a 2.5% increments of deformation in the plaque under the pulsatile blood flow pressure. The IPH also contributed to the increased risk of plaque rupture that a gain of stress was 8.983, 14.526, and 34.47 kPa for the plaque with 50, 65, and 75%, respectively, when comparing stress in the plaque with IPH distributed at the middle to the shoulder of the plaque. In conclusion, neovascularization in the plaque could reduce the stability of the plaque by increasing the stress within the plaque. Also, the risk of plaque rupture increased when large luminal stenosis, thin fibrous cap, and IPH were observed.

Correlation between carotid atherosclerotic plaque properties and serum levels of lncRNA CCAT2 and miRNA-216b.

The purpose of this study was to uncover the clinical values of serum long non-coding RNA (lncRNA) CCAT2 and miRNA-216b in the properties of carotid atherosclerotic plaques. Patients with carotid atherosclerotic plaques were assigned into stable plaque group (n=60) and unstable plaque (n=75) group based on their examination results of cervical contrast-enhanced CT examination. Maximal plaque thickness (MAPT) and intima-media thickness (IMT) in each group were determined. Serum levels of lncRNA CCAT2 and miRNA-216b in patients with carotid atherosclerotic plaques were detected by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Moreover, the correlation between serum levels of CCAT2 and miRNA-216b was analyzed by Pearson's correlation analysis. Besides, potential correlations of serum levels of CCAT2 and miRNA-216b with MAPT and IMT in patients with carotid atherosclerotic plaques were assessed as well. Results revealed that MAPT and IMT were markedly higher in unstable plaque group than those in stable plaque group. Serum level of CCAT2 was higher in unstable plaque group, while miRNA-216b was lower than those in stable group. A negative correlation was identified between serum levels of CCAT2 and miRNA-216b. In addition, CCAT2 level was positively correlated with IMT and MAPT in patients with carotid atherosclerotic plaques, while miRNA-216b level was negatively correlated with them. Detection of serum levels of CCAT2 and miRNA-216b could be applied for predicting the rupture of carotid atherosclerotic plaques. They may be potential biomarkers predicting ischemic stroke.

An investigation into the role of different constituents in damage accumulation in arterial tissue and constitutive model development

Carotid atherosclerotic plaque rupture is one of the leading causes of stroke. Treatments for atherosclerosis can induce tissue damage during the deployment of an intravascular device or through external tissue clamping during surgery. In this paper, a constituent specific study was performed to investigate the role of the ground matrix and collagen fibres of arterial tissue in response to supra-physiological loads. Cyclic mechanical tests were conducted on intact and collagenase-digested strips of porcine common carotid arteries. Using these tests, four passive damage-relevant phenomena were studied, namely (i) Mullins effect, (ii) hysteresis, (iii) permanent set and (iv) matrix failure and fibre rupture. A constitutive model was also developed to capture all of these damage-relevant phenomena using a continuum damage mechanics approach. The implemented constitutive model was fit to experimental results for both intact and digested samples. The results of this work demonstrate the important role of the ground matrix in the permanent deformation of the arterial tissue under high loads. Supra-physiological load-induced tissue damage may play a key role in vascular remodelling in arteries with atherosclerosis or following interventional procedures.

Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques.

Objective:Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention.Data Sources:We searched the PubMed database for recently published research articles up to June 2016, with the key words of “risk factors”, “outcomes”, “blood components”, “molecular mechanisms”, “cellular mechanisms”, and “human carotid atherosclerotic plaques”.Study Selection:The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected.Results:This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque.Conclusion:Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis.

From Ultrasonography to High Resolution Magnetic Resonance Imaging: Towards an Optimal Management Strategy for Vulnerable Carotid Atherosclerotic Plaques

Stroke remains a major cause of death and disability worldwide, with approximately one-third of ischaemic strokes being a consequence of carotid atherosclerotic plaque rupture. Thus, diagnostic strategies that could identify those patients at highest risk of events are of critical importance.

Is the Carotid Plaque Rupture a Pivotal Event in Stroke Pathogenesis? Update on the Role of the Intraplaque Inflammatory Processes

Stroke, a leading cause of death or disability worldwide, is frequently dependent on the rupture of carotid atherosclerotic plaques. It is therefore extremely important to study the mechanisms of formation, progression and eventually rupture of the plaques. Vulnerability of the plaque, the intrinsic tendency to lose its integrity and consequently to induce a dramatic atherothrombotic or embolic event, is still an elusive concept because many players are involved and the clinical picture is frequently the sum of different contrasting (pro-inflammatory and anti-inflammatory) phenomena. This review will discuss recent advancements in the comprehension of this topic. In particular inflammatory activation at the level of the carotid plaque will be described in the attempt to underline the main factors for the formation, the chronic persistence and the risk of rupture. Since these topics can be studied in humans only with plaque samples obtained following endarterectomy, research has tried to evaluate the role of different biomarkers which could be useful for the definition of the vulnerability of a carotid plaque, or, with more clinical relevance, of a patient; some recent results from our group will be discussed. A significant help for clinical decisions may also come from imaging tools, both well established ultrasound and more sophisticated options, such as magnetic resonance and positron emission tomography. This large amount of scientific information should allow the development of new therapeutic approaches for the effective prevention of cerebrovascular events.

In vivo MRI-based simulation of fatigue process: a possible trigger for human carotid atherosclerotic plaque rupture

BackgroundAtherosclerotic plaque is subjected to a repetitive deformation due to arterial pulsatility during each cardiac cycle and damage may be accumulated over a time period causing fibrous cap (FC) fatigue, which may ultimately lead to rupture. In this study, we investigate the fatigue process in human carotid plaques using in vivo carotid magnetic resonance (MR) imaging.MethodTwenty seven patients with atherosclerotic carotid artery disease were included in this study. Multi-sequence, high-resolution MR imaging was performed to depict the plaque structure. Twenty patients were found with ruptured FC or ulceration and 7 without. Modified Paris law was used to govern crack propagation and the propagation direction was perpendicular to the maximum principal stress at the element node located at the vulnerable site.ResultsThe predicted crack initiations from 20 patients with FC defect all matched with the locations of the in vivo observed FC defect. Crack length increased rapidly with numerical steps. The natural logarithm of fatigue life decreased linearly with the local FC thickness (R2 = 0.67). Plaques (n=7) without FC defect had a longer fatigue life compared with those with FC defect (p = 0.03).ConclusionFatigue process seems to explain the development of cracks in FC, which ultimately lead to plaque rupture.

Multimarker Approach in Discriminating Patients with Symptomatic and Asymptomatic Atherosclerotic Carotid Artery Stenosis

Background and PurposeSeveral circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS).MethodsProspective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization.ResultsCS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively).ConclusionsIn an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.

Comparison of Carotid Atherosclerotic Plaque Characteristics by High-Resolution Black-Blood MR Imaging between Patients with First-Time and Recurrent Acute Ischemic Stroke

It has been shown that patients with a first ischemic stroke are at high risk of developing recurrent stroke due to carotid atherosclerotic plaque rupture. However, no one has defined the difference in plaques between initial and recurrent stroke. This study sought to investigate the characteristics of carotid plaque between patients with first-time and recurrent acute ischemic stroke by using MR imaging. Eighty-nine patients with recent acute ischemic stroke were recruited. All subjects underwent carotid high-resolution black-blood MR imaging. The index carotid arteries, defined as the arteries responsible for the ipsilateral stroke, were analyzed quantitatively and qualitatively. Carotid plaque burden and compositional features between patients with first-time and recurrent ischemic stroke were compared. Of 89 recruited patients, 51 had first-time stroke and 38 had recurrent stroke. The mean WA, WT, and PWV were greater in patients with recurrent stroke than in patients with first-time stroke (all, P < .05). Compared with patients with first-time stroke, those with recurrent stroke showed significantly higher prevalence of calcification (44.7% versus 23.5%, P = .035) as well as a larger volume of LRNC (179.14 ± 254.81 mm(2) versus 71.65 ± 111.15 mm(2), P = .027). IPH or fibrous cap rupture or both were observed in 15.8% of patients with recurrent stroke and 3.9% of patients with first-time stroke. Carotid plaques in patients with recurrent ischemic stroke are significantly aggravated compared with those in patients with first-time stroke, and monitoring carotid plaques in patients with initial stroke by MR imaging may be helpful for secondary stroke prevention.

Determination of acute vascular injury and edema in porcine carotid arteries by T2 weighted cardiovascular magnetic resonance

Inflammation plays an essential role for destabilization and rupture of carotid atherosclerotic plaques causing embolic ischemic stroke. Inflammation of the vessel wall may result in the formation of edema. This study investigated whether edema in the carotid artery wall induced by acute balloon injury could be detected by cardiovascular magnetic resonance (CMR) using a T2-weighted short-tau inversion recovery sequence (T2-STIR). Edema was induced unilaterally by balloon injury in the carotid artery of six pigs. Four to nine days (average six) post injury, the carotid arteries were assessed by T2-STIR and multi-contrast weighted sequences. CMR images were matched to histopathology, validated against Evans blue, and correlated with the amount of fibrinogen in the arterial wall used as an edema marker. T2-STIR images showed that the carotid signal intensity (SI) divided by the sternocleid muscle SI of the injured carotid artery was on average 223% (P = 0.03) higher than that of the uninjured carotid artery. Using a threshold value of 4SD, T2-STIR detected edema in the vessel wall (i.e., hyperintense signal intensity) with a sensitivity of 100% and a specificity of 75%. Agreement was observed between carotid artery wall hyperintense signal intensity and Evans blue uptake (X(2) = 17.1, P < 0.001). The relative signal intensity correlated in a linear fashion with the amount of fibrinogen detected by histopathology (ρ = 0.9, P < 0.001). None of the multi-contrast weighted sequences detected edema in the carotid artery with reasonable sensitivity or specificity. T2-STIR CMR allowed carotid artery wall edema detection and may therefore be a useful non-invasive diagnostic tool for determination of inflammatory activity in the carotid artery wall.

Magnetic Resonance Imaging of Carotid Atherosclerotic Plaque in Clinically Suspected Acute Transient Ischemic Attack and Acute Ischemic Stroke

Carotid atherosclerotic plaque rupture is thought to cause transient ischemic attack (TIA) and ischemic stroke (IS). Pathological hallmarks of these plaques have been identified through observational studies. Although generally accepted, the relationship between cerebral thromboembolism and in situ atherosclerotic plaque morphology has never been directly observed noninvasively in the acute setting. Consecutive acutely symptomatic patients referred for stroke protocol magnetic resonance imaging/angiography underwent additional T1- and T2-weighted carotid bifurcation imaging with the use of a 3-dimensional technique with blood signal suppression. Two blinded reviewers performed plaque gradings according to the American Heart Association classification system. Discharge outcomes and brain magnetic resonance imaging results were obtained. Image quality for plaque characterization was adequate in 86 of 106 patients (81%). Eight TIA/IS patients with noncarotid pathogenesis were excluded, yielding 78 study patients (38 men and 40 women with a mean age of 64.3 years, SD 14.7) with 156 paired watershed vessel/cerebral hemisphere observations. Thirty-seven patients had 40 TIA/IS events. There was a significant association between type VI plaque (demonstrating cap rupture, hemorrhage, and/or thrombosis) and ipsilateral TIA/IS (P<0.001). A multiple logistic regression model including standard Framingham risk factors and type VI plaque was constructed. Type VI plaque was the dominant outcome-associated observation achieving significance (P<0.0001; odds ratio, 11.66; 95% confidence interval, 5.31 to 25.60). In situ type VI carotid bifurcation region plaque identified by magnetic resonance imaging is associated with ipsilateral acute TIA/IS as an independent identifier of events, thereby supporting the dominant disease pathophysiology.

Thrombi of Different Pathologies: Implications for Diagnosis and Treatment

Stroke is the second leading cause of cardiovascular mortality in the modern world, accounting for 80% of strokes of ischemic origin. There are two main etiologies of ischemic stroke: 70% to 80% are caused by carotid atherosclerotic plaque rupture and superimposed thrombus formation, whereas 30% are caused by systemic embolism of a cardiac thrombus (mainly in atrial fibrillation [AF] patients). Therefore, antithrombotic therapy is the cornerstone of stroke treatment. In AF patients, thrombotic risk should be assessed by means of the CHADS2 score. Patients with a score of 0 should be treated with aspirin; for those with a score of 1, oral anticoagulation (target international normalized ratio, 2-3) or aspirin is recommended. For patients with a CHADS2 score ≥2, oral anticoagulation with warfarin should be initiated (unless contraindicated). If warfarin is contraindicated, antithrombotic treatment should be prescribed (the combination of aspirin and clopidogrel seems to be superior to aspirin alone). For primary prevention in atherosclerotic patients, low-dose aspirin is useful only in women older than 45years who are not at risk for intracranial hemorrhage and do not have gastrointestinal intolerance (a very small but significant effect). For secondary prevention in atherosclerotic patients, antithrombotic therapy should be administered. It is recommended that patients who do not require anticoagulation receive clopidogrel or a combination of aspirin and dipyridamole. Alternatively, aspirin alone or triflusal may be used. Within 4.5h of onset of acute stroke, thrombolytic therapy (recombinant tissue plasminogen activator) must be injected urgently (unless contraindicated). Dabigatran is a new oral anticoagulant (competitive thrombin inhibitor) with a promising role in stroke prevention; at low doses, it is noninferior to warfarin for stroke prevention and is safer, whereas at high doses, it is superior to warfarin in stroke prevention with the same incidence of bleeding. Percutaneous left atrial appendage occluders recently were approved for systemic embolism prevention. The use of warfarin after implantation is still under discussion. Dronedarone, a new antiarrhythmic agent, has been shown to decrease cardiovascular mortality and stroke in patients with AF. Carotid endarterectomy surgery is indicated in symptomatic patients with stenosis greater than 70% and in selected patients with 50% to 70% stenosis. Currently, carotid endarterectomy surgery is superior to carotid angioplasty and stenting.

Carotid plaque instability and ischemic symptoms are linked to immaturity of microvessels within plaques

Instability and rupture of carotid atherosclerotic plaques leads to thromboemboli and ischemic symptoms. Angiogenesis occurs within atherosclerotic plaques, and plaque vulnerability and symptomatic carotid disease have been associated with increased numbers of microvessels. In addition to microvessel number, it is possible that the phenotypes of intraplaque vessels could influence plaque stability. To test this, the morphology and maturity of vessels within plaques from symptomatic and asymptomatic patients was determined. Carotid plaques were collected after endarterectomy from a cohort of 13 asymptomatic patients and 30 symptomatic patients. Plaques were sectioned and immunostained for the presence of endothelial cells, vascular smooth muscle cells, macrophages, and vascular endothelial growth factor. Sections were assessed for microvessel morphology, maturity as judged by smooth muscle cell cover, and the presence of vascular endothelial growth factor and macrophages. Two types of vascular structure were observed within plaques, microvessels and dilated, highly irregular multilobular vessels. These irregular dysmorphic vessels were found almost exclusively in plaques from symptomatic patients. The dysmorphic vessels lacked smooth muscle cells and were highly immature. Plaques also contained vascular endothelial growth factor, and this was observed adjacent to the dysmorphic vessels. This growth factor was found colocalized with macrophages. Symptomatic carotid plaques contain abnormal, immature microvessels similar to those found in tumors and healing wounds. Such vessels could contribute to plaque instability by acting as sites of vascular leakage by inflammatory cell recruitment. The immature vessels within plaques may be therapeutic targets for promoting plaque stabilization.