Normal Carotid Arteries Research Articles

Guidelines for Assessing Mouse Endothelial Function via Ultrasound Imaging: a Report from the International Society of Cardiovascular Translational Research

The study is to establish a novel method to determine the endothelial function in mouse carotid arteries in vivo by using high-resolution ultrasound images. Atherosclerosis in carotid arteries is induced in ApoE(-/-) mice with a Western diet. The ultrasound of the ventral neck generates clear pictures of the common carotid arteries. Acetylcholine at the range from 5 to 20 μg/kg/min (iv) is able to induce a dose-dependent relaxation as shown by the increased diameter of these normal mouse carotid arteries, which is impaired in atherosclerotic arteries. The endothelial function determined by ultrasound images in vivo matches well with that determined in isolated carotid arterial rings in vitro. All animals survived after the endothelial function measurement. In this study, we have established a standard method to determine the mouse endothelial function in vivo. It is a reliable, safe, and survival method that could be used repetitively in mouse arteries.

Establishment of a rabbit model of coronary artery bypass graft and endothelial nitric oxide synthase gene transfection.

This study established an animal model of coronary artery bypass graft (CABG) surgery. The human endothelial nitric oxide synthase (eNOS) gene was transfected into grafted arterial walls to verify transfection efficiency. Forty rabbits were randomized into the following 4 equal groups: 1) eNOS gene transfection group (eNOS group); 2) empty eNOS gene transfection group (empty gene group); 3) control group; 4) normal femoral artery group. Grafted arteries, and normal carotid and femoral artery specimens were obtained 3 weeks later. Immunohistochemistry and analyses of tissue nitric oxide (NO) levels, eNOS activity, and eNOS protein western blotting were performed. The effectiveness and efficiency of transfection were observed and confirmed. All rabbits survived. The grafted arteries retained patency. Varying degrees of adaptability changes were observed in grafted arteries in each group. The eNOS group exhibited vascular wall thickening and significantly increased eNOS protein expression. The control and empty gene groups exhibited vessel wall degeneration, and eNOS protein was weakly or not expressed (P < 0.05). The arterial wall NO concentration and total eNOS activity in the eNOS group were significantly higher than those in the other groups (P < 0.05). Western blotting demonstrated that the vascular wall eNOS protein concentration was significantly greater than that in the other groups (P < 0.05). Furthermore, the eNOS gene transfection can increase eNOS expression and activity in vessel walls, increasing local NO concentration and expression.

Age and disease-related geometric and structural remodeling of the carotid artery

Carotid artery geometry has been suggested as a risk factor for atherosclerotic carotid artery disease (ACD). Although normal aging and development of disease can both lead to geometric changes in the artery, whether geometric changes in a given artery actually predispose to disease or are just a consequence of remodeling during aging is unclear. We investigated carotid artery geometric changes with aging to identify geometric features associated with the presence of ACD. Carotid artery geometry was quantified by measuring carotid artery diameter, tortuosity, and bifurcation angle using three-dimensional reconstructions of thin-section computed tomography angiography scans in 15 healthy individuals (average age, 43 ± 18 years; range, 15-64 years). The same geometric features were measured in 17 patients (68 ± 10 years old) with unilateral ACD. Geometric features associated with presence of ACD were determined by using the nondiseased contralateral carotid artery as an intrinsic control. Elastin-stained carotid arteries were analyzed to assess age-related structural changes in 12 deceased individuals. Increases were noted in bulb diameter (0.64 mm), bifurcation angle (10°), and tortuosity of the common carotid (CCA; 0.03) and internal carotid arteries (ICA; 0.04) for every decade of life. Density and continuity of circumferential and longitudinal elastin in the CCA and ICA decreased with age. Compared with normal carotid arteries, those with ACD demonstrated larger bulb diameters (P = .001) but smaller bifurcation angles (P = .001). CCA tortuosity (P = .038) increased in ACD arteries compared with normal carotid arteries, but ICA tortuosity was decreased (P = .026). With increasing age, bulb diameter, tortuosity, and bifurcation angle increases in carotid arteries. These geometric changes may be related to degradation and fragmentation of intramural elastin. Arteries with atherosclerotic occlusive disease demonstrate decreased ICA tortuosity and smaller bifurcation angles compared with nondiseased carotid arteries.

Mechanical instability of normal and aneurysmal arteries

Tortuous arteries associated with aneurysms have been observed in aged patients with atherosclerosis and hypertension. However, the underlying mechanism is poorly understood. The objective of this study was to determine the effect of aneurysms on arterial buckling instability and the effect of buckling on aneurysm wall stress. We investigated the mechanical buckling and post-buckling behavior of normal and aneurysmal carotid arteries and aorta’s using computational simulations and experimental measurements to elucidate the interrelationship between artery buckling and aneurysms. Buckling tests were done in porcine carotid arteries with small aneurysms created using elastase treatment. Parametric studies were done for model aneurysms with orthotropic nonlinear elastic walls using finite element simulations. Our results demonstrated that arteries buckled at a critical buckling pressure and the post-buckling deflection increased nonlinearly with increasing pressure. The presence of an aneurysm can reduce the critical buckling pressure of arteries, although the effect depends on the aneurysm’s dimensions. Buckled aneurysms demonstrated a higher peak wall stress compared to unbuckled aneurysms under the same lumen pressure. We conclude that aneurysmal arteries are vulnerable to mechanical buckling and mechanical buckling could lead to high stresses in the aneurysm wall. Buckling could be a possible mechanism for the development of tortuous aneurysmal arteries such as in the Loeys–Dietz syndrome.

The cytokines within the carotid plaque in symptomatic patients with internal carotid artery stenosis.

Materials and methodsThe experiment was carried out on 100 symptomatic patients with internal carotid artery stenosis that underwent carotid endarterectomy. Every patient had the wall of the carotid artery resected during organ harvesting surgery in order to evaluate some cytokines (TGF-β, VEGF, FGF, TNF-α) and to perform the immunohistochemistry (IHC). An immunoreactive score (IRS) was calculated based on the staining intensity and the number of cells stained. Over a 3-year period, 7 patients died, and 2 patients were lost to follow-up. The study group consisted of 91 patients. The control group comprised 20 young organ donors with confirmed death brain, who had their normal carotid artery sampled.ResultsIn all healthy donors (control group) with normal carotid arteries the three cytokines (TGF-β, VEGF, TNF-α) were not discovered. The presence of FGF was confirmed in 25% of healthy donors, probably due to an intima fibroblasts activity, responsible for the synthesis of elastin and collagen to the extracellular matrix (ECM). Only three cytokines (TGF-β, FGF, TNF-α) were found within atheromatous plaques (study group).ConclusionsOur research confirmed that these factors may accelerate the development of atheromatic plaque and its destabilisation.The aim of the study was the evaluation of the inflammatory cytokines within atheromatic carotid plaque.Electronic supplementary materialThe online version of this article (doi:10.1186/1749-8090-9-139) contains supplementary material, which is available to authorized users.

HOXA1 Mutations are Not Commonly Associated with Non-Syndromic Deafness.

Homozygous homeobox A1 (HOXA1) mutations cause a spectrum of abnormalities in humans including bilateral profound deafness. This study evaluates the possible role of HOXA1 mutations in familial, non-syndromic sensorineural deafness. Forty-eight unrelated Middle Eastern families with either consanguinity or familial deafness were identified in a large deafness clinic, and the proband from each family was evaluated by chart review, audiogram, neuroimaging, and HOXA1 sequencing. All 48 probands had normal neuro-ophthalmologic and general medical examinations except for refractive errors. All had congenital non-syndromic sensorineural hearing loss that was symmetric bilaterally and profound (>90 dBHL) in 33 individuals and varied from 40 to 90 dBHL in the remainder. Thirty-nine of these individuals had neuroimaging studies, all documenting normal internal carotid arteries and normal 6th, 7th, and 8th cranial nerves bilaterally. Of these, 27 had normal internal ear structures with the remaining 12 having mild to modest developmental abnormalities of the cochlea, semicircular canals, and/or vestibular aqueduct. No patient had homozygous HOXA1 mutations. None of these patients with non-syndromic deafness had HOXA1 mutations. None had major inner ear anomalies, obvious cerebrovascular defects, or recognized congenital heart disease. HOXA1 is likely not a common cause of non-syndromic deafness in this Middle Eastern population.

The normal internal carotid artery: a computed tomography angiographic study.

Systematic computed tomography angiographic (CTA) studies investigating variation in internal carotid artery (ICA) luminal diameters (LDs) are scarce. Knowledge of the normal intra-individual LD variability would provide a cut-off value for detection of more subtle collapses. In addition, low intra-individual variability would allow using contralateral LD as a reference for estimation of stenosis degree in cases where ipsilateral measurement is hampered. Therefore, our aim was to investigate intra-individual LD variation of normal ICA. We retrospectively collected multidetector high-speed CTAs of 104 patients younger than 40 years who were considered not to have carotid pathology. We carried out independent measurements of the common carotid artery (CCA) and ICA LDs bilaterally from axial source images by two observers, analysing side-to-side LD differences from averaged double measurements with a paired t test. We discovered no significant side-to-side LD differences. In the female group, the mean differences (mm) with 95% confidence intervals were 0.08 (0.00, 0.17) for CCA and 0.03 (-0.04, 0.11) for ICA, with ICA LD standard deviation of 0.4 mm. In the male group, these were: 0.06 (-0.04, 0.17), 0.02 (-0.07, 0.11) and 0.4 mm, respectively. We detected no ICA agenesis. The intrinsic intra-individual variation of the LD of normal ICA is minimal. This uniformity may serve as the basis for detection of subtle grades of side-to-side variation caused by pathology.

Simultaneous Thrombosis in a Normal Left Ventricle and Normal Carotid Artery in a Patient With a Stroke Secondary to Iron Deficiency Anemia

Iron deficiency anemia (IDA) is implicated as a cause of stroke, particularly in young patients without cardiovascular disease. In such patients, thrombi sometimes form in carotid arteries or the aorta. We report here a patient with a stroke secondary to IDA with thrombi in the normal left ventricle and normal carotid artery. The patient was a 45-year-old woman with severe IDA who developed cerebral infarction in the right middle cerebral artery. She had no other thrombophilia or cardiovascular diseases. Echocardiography showed a left ventricular thrombus without cardiac disease, and the carotid ultrasound showed a mobile thrombus attached to the right internal carotid artery without atherosclerosis. Antithrombotic therapy with iron supplementation removed both thrombi within 2 weeks. This is the first case of IDA with a ventricular thrombus in a normal heart. This case identifies a new site for thrombosis in IDA and shows that patients with IDA may present with simultaneous thrombosis at separate sites. IDA must therefore be recognized as a cause of stroke or systemic embolism, particularly in patients without detectable cardiovascular disease. In such patients, it is important to conduct careful investigations to detect thrombosis. J Med Cases. 2014;5(6):351-354 doi: http://dx.doi.org/ 10.14740 /jmc1786w

Abstract 169: Smad3 Drives Cross-Talk Between TGFß and Wnt/ß-Catenin Signaling Pathways in Smooth Muscle Cells

Restenosis (neo-intimal hyperplasia) occurs in approximately 25-50% of patients undergoing arterial interventions, primarily due to the proliferation and migration of arterial smooth muscle cells (SMCs) into the peri-luminal area. Recently, Wnt/β-catenin signaling has been shown to promote SMC proliferation and enhance neo-intimal hyperplasia but its mechanism of activation is unclear. Interestingly, Wnt/β-catenin has been shown to be activated by TGFβ in mesenchymal stem cells and fibroblasts. We have shown that TGFβ and its downstream signaling protein, Smad3, are upregulated following vascular injury and that Smad3 overexpressing SMCs display enhanced proliferation, migration, and neo-intimal hyperplasia. These results led us to hypothesize that TGFβ, through Smad3, activates Wnt/β-catenin to regulate SMC behavior following arterial injury . In primary rat SMCs, TGFβ (5ng/mL) led to β-catenin activation and relocalization from the plasma membrane to the cytoplasm / nucleus within 24 hours. Furthermore, qRT-PCR results demonstrated that expression of Wnt11 (22 fold) and Wnt9a (3.9 fold) were significantly upregulated after 24 hours of TGFβ stimulation (p&lt;0.05, n=3). In addition, 24 hours of TGFβ stimulation in SMCs overexpressing Smad3 (TGFβ/Smad3) further enhanced the gene expression of Wnt11 (&gt;300 fold) and Wnt9a (14 fold) and also stimulated significant increases in Wnt2b (41 fold), Wnt5a (2.9 fold), and Wnt4 (3.2 fold) (p&lt;0.05, n=3) as measured by qRT-PCR. Western blot results demonstrated that the combined TGFβ/Smad3 stimulation increased β-catenin protein levels, suggesting that TGFβ activates canonical Wnt signaling leading to stabilization of β-catenin protein. In normal rat carotid arteries, β-catenin protein was undetectable via immunohistochemistry but could be seen in SMCs of the vessel media at 3 days post-balloon angioplasty and in neo-intimal cells at 7 and 14 days. Smad3 was also expressed in neo-intimal cells at 7 and 14 days post-angioplasty suggesting that TGFβ, through Smad3, is responsible for Wnt/β-Catenin activation during vascular injury. In conclusion, this work describes a novel cross-talk in SMCs between TGFβ and Wnt signaling which may provide a viable target for future anti-restenotic treatments.

Closure technique after carotid endarterectomy influences local hemodynamics

Meta-analysis supports patch angioplasty after carotid endarterectomy (CEA); however, studies indicate considerable variation in practice. The hemodynamic effect of a patch is unclear and this study attempted to elucidate this and guide patch width selection. Four groups were selected: healthy volunteers and patients undergoing CEA with primary closure, trimmed patch (5 mm), or 8-mm patch angioplasty. Computer-generated three-dimensional models of carotid bifurcations were produced from transverse ultrasound images recorded at 1-mm intervals. Rapid prototyping generated models for flow visualization studies. Computational fluid dynamic studies were performed for each model and validated by flow visualization. Mean wall shear stress (WSS) and oscillatory shear index (OSI) maps were created for each model using pulsatile inflow at 300 mL/min. WSS of <0.4 Pa and OSI >0.3 were considered pathological, predisposing to accretion of intimal hyperplasia. The resultant WSS and OSI maps were compared. The four groups comprised 8 normal carotid arteries, 6 primary closures, 6 trimmed patches, and seven 8-mm patches. Flow visualization identified flow separation and recirculation at the bifurcation increased with a patch and was related to the patch width. Computational fluid dynamic identified that primary closure had the fewest areas of low WSS or elevated OSI but did have mild common carotid artery stenoses at the proximal arteriotomy that caused turbulence. Trimmed patches had more regions of abnormal WSS and OSI at the bifurcation, but 8-mm patches had the largest areas of deleteriously low WSS and high OSI. Qualitative comparison among the four groups confirmed that incorporation of a patch increased areas of low WSS and high OSI at the bifurcation and that this was related to patch width. Closure technique after CEA influences the hemodynamic profile. Patching does not appear to generate favorable flow dynamics. However, a trimmed 5-mm patch may offer hemodynamic benefits over an 8-mm patch and may be the preferred option.

Abstract T P94: Association Between Carotid Expansive Remodeling Determined by Long-axis High-resolution MRI and Unstable Clinical Presentation

Background and Purpose: Accumulating evidence from recent vascular biology studies has demonstrated that not only luminal narrowing but also plaque characteristics have large impact on the risk of ischemic events. The impact of expansive remodeling (ER) in atherosclerotic arterial disease on unstable clinical presentation has been extensively investigated in coronary circulation. The purpose of the present study was to investigate the association between carotid ER determined by MRI and cerebral ischemic events. Methods: Among prospectively collected data for patients with carotid artery (CA) stenosis scheduled for carotid endarterectomy (CEA) or carotid stenting, 122 CAs in 119 patients were identified. Excluding 22 CAs (contraindicated for MRI due to pacemaker implantation: 2, near-occlusion: 8, inadequate MRI due to poor image quality: 6, restenosis after CEA or CAS: 6), 100 CAs were finally analyzed in this study. The study included 50 symptomatic (73.6 ± 8.9 years; 6 female; %stenosis, 68.5± 21.3; 34 CEA) and 50 asymptomatic lesions (72.0 ± 5.9 years; 5 female; %stenosis, 79.4 ± 8.85; 15 CEA). ER ratio was calculated by dividing the maximal outside diameter at atherosclerotic plaque near the carotid bulb by the maximal outside diameter of the normal internal CA distal to the plaque with use of long-axis high-resolution MRI. Results: In 25 patients with unilateral carotid atherosclerosis, the ER ratio of atherosclerotic CA (1.68±0.40) was significantly greater (p&lt;.01) than that of the normal physiological expansion at a carotid bulb (1.36±0.15). The ER ratio of symptomatic CAs (1.93±0.44) was significantly greater (p&lt;0.0001) than that of asymptomatic CAs (1.63±0.30). When the cutoff value was set as 1.88, sensitivity and specificity were 0.6 and 0.78, respectively. The ER ratio of symptomatic CAs was consistently high regardless of % luminal stenosis. Conclusions: ER ratio measured with MRI might help to establish more accurate risk stratification for future cerebral ischemic events.

Simultaneous Thrombosis in a Normal Left Ventricle and Normal Carotid Artery in a Patient With a Stroke Secondary to Iron Deficiency Anemia

Iron deficiency anemia (IDA) is implicated as a cause of stroke, particularly in young patients without cardiovascular disease. In such patients, thrombi sometimes form in carotid arteries or the aorta. We report here a patient with a stroke secondary to IDA with thrombi in the normal left ventricle and normal carotid artery. The patient was a 45-year-old woman with severe IDA who developed cerebral infarction in the right middle cerebral artery. She had no other thrombophilia or cardiovascular diseases. Echocardiography showed a left ventricular thrombus without cardiac disease, and the carotid ultrasound showed a mobile thrombus attached to the right internal carotid artery without atherosclerosis. Antithrombotic therapy with iron supplementation removed both thrombi within 2 weeks. This is the first case of IDA with a ventricular thrombus in a normal heart. This case identifies a new site for thrombosis in IDA and shows that patients with IDA may present with simultaneous thrombosis at separate sites. IDA must therefore be recognized as a cause of stroke or systemic embolism, particularly in patients without detectable cardiovascular disease. In such patients, it is important to conduct careful investigations to detect thrombosis. J Med Cases. 2014;5(6):351-354 doi: http://dx.doi.org/ 10.14740 /jmc1786w

Takayasu’s arteritis with left main stem stenosis of single coronary artery

Takayasu’s arteritis is a chronic vasculitis involving the aorta and its main branches, pulmonary arteries, and coronary tree. Coronary involvement may appear in up to one-third of patients with Takayasu’s arteritis. Occlusion of the ostia of the left main coronary artery and of proximal segments of the coronary arteries is the most frequent finding of the coronary vasculature in patients with Takayasu’s arteritis. A 58-year-old male patient with Takayasu’s arteritis admitted to our hospital with atypical chest pain. On the physical examination, there was no palpable pulse of the left radial artery, and a right-sided systolic carotid bruit was identified. Due to positive ischemic response to exercise and his physical examination findings, we decided to perform coronary angiography and aortography, which showed total occlusion of the left subclavian artery (white arrows in Figures A and C) and severe stenosis of the right brachiocephalic artery (black arrows in Figures A and B), with a normal left carotid artery giving collateral arteries to the left subclavian artery. On coronary angiogram, the left main coronary arterial stenosis (black arrows in Figures D and F) and a single coronary artery with anomalous origin of the right coronary artery from the mid left anterior 221

Comorbidities in combined retinal artery and vein occlusions

BackgroundSeveral general diseases cause blindness in patients with simultaneous combined retinal artery and vein occlusion.Methods/patientsWe examined 14 patients with acute unilateral visual loss due to combined retinal artery and venous occlusions. All 14 patients presented at the Polyclinic over a period of about 3 years. Fluorescein angiography was carried out in 12 patients to confirm the diagnosis. Ten patients underwent Doppler sonography and 11 echocardiography.ResultsConcerning systemic diseases, 11 of our 14 patients presented several cardiovascular risk factors, i.e., immunocytoma and arterial hypertension and hypercholesterolemia in one patient; another patient had chronic bronchitis, tachycardia and hypercholesterolemia. Six patients presented coagulation anomalies, and eight patients had arterial hypertension.Doppler sonography revealed normal carotid arteries in nine of ten patients. In 8 of 11 patients, echocardiography displayed no cardiac abnormalities.Ophthalmoscopy revealed no emboli in any of these patients.ConclusionUnilateral simultaneous combined incomplete retinal artery and venous occlusions should be considered as one entity. Eleven of our patients presented comorbidities reflecting several cardiovascular risk factors. Immunological diseases, malignancies and coagulopathies can cause this ocular disorder, resulting in blindness. No emboli were found in any of these patients. Patients suffering from acute visual loss must be examined for the presence of systemic diseases to enable therapy at an early stage.

Subclinical atherosclerosis: independent predictor of cardiovascular events in a 20-years follow up of patients with or without metabolic syndrome

Purpose: To evaluate the influence of carotid atherosclerosis and metabolic syndrome (MetS) on the prediction of cardiovascular events during a 20-years follow-up. Methods: We studied a population of 529 asymptomatic patients, divided into 2 groups according to the results of the carotid ultrasound evaluation: one without atherosclerotic lesions (198 patients) and a second one with an increased carotid IMT or asymptomatic carotid plaque (331 patients). In each of these groups, we identified two subgroups of subjects with and without MetS. Cardiovascular endpoints were investigated in a 20-years follow-up: acute myocardial infarction, angina, transient ischemic attack, ischemic stroke, abdominal aortic aneurysm, thromboendarterectomy and cardiovascular death. Results: During the follow-up there were 242 cardiovascular events, 144 among patients with MetS (251 patients) and 98 among healthy controls (178 patients) (57.4% vs. 35.2%; P<0.0001). Moreover 63 events occurred in patients with normal carotid arteries while 179 events occurred in patients with subclinical atherosclerosis (31.8% vs. 54.1%; P<0.0001). Among 144 total events occurred in patients with MetS, 36 happened in the subgroup of 80 patients with normal carotid arteries and 108 happened in the subgroup of 171 patients with subclinical atherosclerosis (45% vs. 63.15%; P=0.01). Among 98 total events occurred in patients without MetS, 27 developed in the subgroup of 118 patients with normal carotid arteries and 71 occurred in the subgroup of 160 patients with subclinical atherosclerosis (22.9% vs. 44.4%; P=0.0003). In addition among 63 total events occurred in patients without atherosclerotic lesions, 36 events happened in the subgroup of 80 patients with MetS and 27 events occurred in the subgroup of 118 patients without MetS (45% vs. 22.9%; P=0.0018). Finally, among 179 total events recorded in patients with atherosclerotic lesions 108 events happened in the subgroup of 171 patients with MetS and 71 events happened in the subgroup of 160 patients without MetS (63.15% vs. 44.4%; P=0.0009). The Kaplan-Meier function showed an improved survival in patients without atherosclerotic lesions compared with patients with carotid ultrasound alterations (P=0.0159, HR: 0.7366, CI: 0.5479 to 0.9904). Conclusions: Subclinical atherosclerosis lead to an increased risk of cardiovascular events, especially if it is associated with MetS. Therefore we suggest to investigate the presence of subclinical atherosclerosis in all patients with more than 45 years with cardiovascular risk factors for a better stratification of the global cardiovascular risk.

Fly through ultrasound imaging in assessment of carotid atherosclerosis: a pictorial essay

To assess fly through ultrasound imaging (FTUS) in evaluation of carotid artery atherosclerosis, we prospectively performed conventional sonography and FTUS of the carotid artery on 66 patients with suspicion for atherosclerosis. Characteristics of arterial intima, atherosclerotic plaque, luminal narrowing, and carotid stent graft displayed on FTUS were compared with that on conventional sonography. On FTUS, normal carotid artery wall was smooth in appearance, mild carotid atherosclerosis appeared focal arterial wall irregularity and small plaque formation, arterial luminal reduction resulted from progressive artery plaques, and carotid stent had irregular inner lumen and tight fit against the arterial wall. A total of 38 plaques were detected by conventional sonography, while 48 plaques were depicted by FTUS in 25 patients. Using magnetic resonance angiography as a reference standard, 17 cases with >50% and 3 cases with <50% luminal reduction measured on FTUS. However, all those 20 cases were measured with >50% luminal reduction on conventional sonography. Compared with conventional sonography, FTUS can dynamically display intraluminal structure on real-time three-dimensional imaging morphologically to improve the accuracy in detecting atherosclerotic plaque and assessing luminal narrowing in the carotid artery.

Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis

Absent in melanoma (AIM2) was recently identified to act as a cytosolic DNA sensor in innate immunity. Considering the role of chronic inflammation in atherosclerosis, we hypothesized that AIM2 may act as a damage signal that is activated in response to cellular stress likewise in vascular cells of larger arteries. We thus addressed AIM2 expression in healthy arterial wall and in different vascular lesions. In addition, AIM2 expression was characterized in cultured human aortic endothelial cells (HAoECs), smooth muscle cells (HAoSMCs), and T/G-HA-vascular smooth muscle cells (VSMCs) in response to different stimuli. Carotid and aortic lesions from patients who underwent surgery and normal arterial specimens were analyzed by immunohistochemistry for AIM2 expression. Cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs were stimulated in vitro with proinflammatory cytokines (tumor necrosis factor-α, interferon-γ) or poly(dA:dT) and analyzed for AIM2 transcript and protein expression. AIM2 was detected in ECs of the intima and vasa vasorum of normal carotid artery and aorta. Moreover, AIM2 was moderately expressed in VSMCs of normal media and intima layers, as well as in VSMCs of atherosclerotic lesions. Increased AIM2 expression was detected around the necrotic core of atherosclerotic carotid lesions and in the vasa vasorum neovasculature of aortic aneurysms. Subsequent in vitro analysis identified an endogenous AIM2 expression in cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs that was markedly increased upon treatment of the cells with tumor necrosis factor-α, interferon-γ, or cytosolic DNA. ECs and VSMC are able to respond to inflammatory signals by upregulation of AIM2 expression, indicating a role of AIM2 in vascular pathogenesis.

The Maya Behind Moyamoya--The Two Extremes of the Disease : Correspondence

To the Editor: We read with great interest the article by Vijayakanthi N et al. [1]. The brief report describes two patients of pediatric moyamoya disease with extreme presentation. However, we would like to point out certain issues relevant to the disease in question. These presentations cannot be termed extreme as the natural history of moyamoya is variable. Disease progression can be slow, with rare, intermittent events, or fulminant, with rapid neurologic decline. In pediatric population, there are multitude of symptoms associated with moyamoya disease, including transient ischemic attack, ischemic strokes, intracranial hemorrhages, seizures, headaches, choreiform movements, and cognitive deficits. Recently researchers have also reported asymptomatic cases of moyamoya and approximately half of them remained clinically asymptomatic over a mean follow up period of 5.4 y [2]. Thus, it is not unusual to see these variable presentations ofmoyamoya. The variations result possibly from the rapidity and extent of stenosis of intracranial vessels and the patient’s ability to develop effective collaterals [3]. Authors have described that both patients had unilateral finding on angiography. As per the guidelines on the diagnosis and treatment of spontaneous occlusion of circle of willis (Moyamoya disease) unilateral involvement qualifies a diagnosis of a probable case of moyamoya disease instead of definitive case of moyamoya disease [4]. The authors have not mentioned, how was the diagnosis of moyamoya disease concluded in the absence of any collaterals in case-2. As per the diagnostic criteria presence of collaterals on angiography is essential for qualifying a diagnosis of moyamoya disease [4]. Further, how do the authors explain the bilateral findings on clinical examination and MRI brain, but narrowing of only left internal carotid artery with normal right internal carotid artery. The authors have quoted the study by Mugikura et al. [5] for explaining severe presentation in early onset (<4 y of age) moyamoya disease, but in the current case (2nd case) there was no involvement of posterior cerebral artery, thus whether this hypothesis of advanced posterior cerebral artery stenosis leading to severe clinical presentation can be applied to the present case is not clear. Further the hypothesis proposed by Mugikara S et al. also needs confirmation by prospective studies. Finally, it is not clear whether the authors had excluded secondary causes of angiographic moya moya i.e., moya moya syndrome and whether these cases were indeed moya moya disease (idiopathic). At the end “The Maya behind Moyamoya” still remains elusive.

Asymptomatic carotid artery stenosis and correlation with coronary artery stenosis among 200 patients undergoing cabg

Aim: To study the incidence of asymptomatic carotid artery stenosis among patients undergoing CABG.To find its correlation with age,sex and any predilection to side and site of carotid artery. Methods: Doppler ultrasound of carotid arteries was done in 200 patients undergoing Carotid Artery Bypass Grafting (CABG). Patients including both sexes were aged between 35 and 75 years. Patients without any pre existing neurological deficits in the last 6 months were included in the study. Results: Among the study population, 34 cases (17%) of carotid artery stenosis cases were found. The highest number of patients 17 (50%) was found in the age group of 56-65 years. The prevalence of carotid artery stenosis among patients aged more than 55 years (21.5%) is significantly high (p<0.05), than patients less than 55 years (10.1%) old.Out of 34 cases, 38% had bilateral carotid artery stenosis, 32% had right side and 30% had left side carotid stenosisThe commonest site involved was at carotid bulb and internal carotid artery (CB and ICA) in 61.9% of cases.The average IMT of patients who had normal carotid arteries was found to be 0.1193mm on right side and 0.1151mm on left side. Conclusions: Males are at more risk than females. In the age group of 56-65yrs,there is a peak incidence of asymptomatic carotid artery stenosis. The carotid stenosis is highly prevalent among patients with severe coronary artery disease.Atherosclerosis predominantly affects the carotid artery bifurcation due to its typical flow characteristics. The average IMT of carotid arteries of indian patients who had normal carotid arteries was found to be 0.1193mm on right side and 0.1151mm on left side.

Effect of Velocity Profile Skewing on Blood Velocity and Volume Flow Waveforms Derived From Maximum Doppler Spectral Velocity

Given evidence that fully developed axisymmetric flow may be the exception rather than the rule, even in nominally straight arteries, maximum velocity (Vmax) can lie outside the Doppler sample volume (SV). The link between Vmax and derived quantities, such as volume flow (Q), may therefore be more complex than commonly thought. We performed idealized virtual Doppler ultrasound on data from image-based computational fluid dynamics (CFD) models of the normal human carotid artery and investigated how velocity profile skewing and choice of sample volume affected Vmax waveforms and derived Q variables, considering common assumptions about velocity profile shape (i.e., Poiseuille or Womersley). Severe velocity profile skewing caused substantial errors in Vmax waveforms when using a small, centered SV, although peak Vmax was reliably detected; errors with a long SV covering the vessel diameter were orientation dependent but lower overall. Cycle-averaged Q calculated from Vmax was typically within ±15%, although substantial skewing and use of a small SV caused 10%–25% underestimation. Peak Q derived from Womersley's theory was generally accurate to within ±10%. Vmax pulsatility and resistance indexes differed from Q-based values, although the Q-based resistance index could be predicted reliably. Skewing introduced significant error into Vmax-derived Q waveforms, particularly during mid-to-late systole. Our findings suggest that errors in the Vmax and Q waveforms related to velocity profile skewing and use of a small SV, or orientation-dependent errors for a long SV, could limit their use in wave analysis or for constructing characteristic or patient-specific flow boundary conditions for model studies.