Small Vessel Disease Stroke Research Articles

Thrombolysis in Posterior Circulation Stroke: Stroke Subtypes and Patterns, Complications and Outcome

Background: Patients with posterior circulation stroke (PCS) were underrepresented in or even excluded from the large clinical trials investigating acute therapy with thrombolysis. Therefore, the knowledge about potential benefits and risks of thrombolysis in PCS is sparse. Methods: From July 2004 until June 2007, 237 stroke patients were treated with thrombolysis within 3 h after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of patients with PCS were compared to those with anterior circulation stroke (ACS). Results: There were 30 patients in the PCS group; 198 had ACS. In the PCS group, less patients had a history of prior stroke (0/30 vs. 31/198 (15.7%), p = 0.02) and less were treated with platelet inhibitors (6/30 (20.0%) vs. 83/198 (41.9%), p = 0.02). Onset to treatment time was higher in the PCS group (156.2 ± 23.2 vs. 141.1 ± 30.7, p = 0.01). Small vessel disease occurred more often in PCS patients (10/30 (33.3%) vs. 12/198 (6.1%), p < 0.001), whereas stroke of undetermined cause was less frequent (5/30 (16.7%) vs. 75/198 (37.9%), p = 0.02). Correspondingly, PCS patients had more lacunar (13/30 (43.3%) vs. 15/198 (7.3%), p < 0.001) strokes on CT/MRI. Patients with PCS had significantly lower median NIHSS scores after 2 and 24 h, whereas the median NIHSS and mRS scores at discharge as well as the mRS score at the 3-month follow-up, although still lower, did not differ significantly between both groups. Outcome was similar with regard to complications and mortality. Conclusions: Patients with PCS have a higher rate of small vessel disease and lacunar stroke. In terms of potential benefits and risks of thrombolysis, we could demonstrate no significant differences between PCS and ACS. Acute PCS patients should be diagnosed and treated with the same elaborateness as ACS patients.

Biomarkers to predict clinical progression in small vessel disease strokes: Prognostic role of albuminuria and oxidized LDL cholesterol

ObjectiveClinical progression in lacunar strokes (LS) is an unpredictable and fearful complication. Endothelial dysfunction (ED) is believed to be the first step in the pathophysiology of LS therefore we aimed to analyze the association of three markers of ED: albuminuria, von Willebrand factor (vWF), and oxidized LDL cholesterol (ox-LDL) with LS progression. MethodsFrom December 2007 to December 2010, 127 LS patients admitted within 6h of symptom onset were prospectively assessed. Progression was defined as initial NIHSS score worsening ≥4 points within the first 72h. Analysis of vWF and ox-LDL was done at admission. Albuminuria was measured in the first morning spot urine. Association between 3 biomarkers and progression was tested using logistic regression analysis. Other clinical variables of interest were also studied. Discriminative power was analyzed with a receiver operator curve. ResultsTwenty-two patients (17.3%) progressed. Progression was associated with worse outcome at 90 days. Albuminuria and ox-LDL were associated in univariate analysis; vWF was not. Adjusted OR were: ox-LDL [OR: 1.03; 95% CI: 1.01–1.07, p=0.019], albuminuria [OR: 2.07; 95% CI: 1.04–4.13, p=0.039]. Association was linear without a cut-off point. Clinical variables were not associated with progression. The model including albuminuria and ox-LDL had a good predictive value [AUC: 0.80 [0.70–0.89)]. ConclusionsAlbuminuria and ox-LDL levels are independently associated with higher risk of progression in LS. The lack of reliable clinical predictors makes biomarker research a priority to improve progression detection in this subtype of ischemic strokes.

Unravelling the Genetics of Ischaemic Stroke

Epidemiological studies suggest genetic predisposition is important in stroke risk. Monogenic conditions are important for the individual patient but do not account for much population attributable risk. An increasing number of such conditions are being described, particularly for the small vessel disease stroke subtype. The candidate genes approach has proved disappointing in identifying genes contributing to the risk of multifactorial or polygenic stroke. This is a situation shared with other complex diseases. Recently the GWAS (genome-wide association study) approach has identified genetic loci for many other cardiovascular diseases such as coronary heart disease, diabetes, and hypertension, and is just being applied to stroke. Some novel genetic variants initially associated with other cardiovascular diseases have recently been identified as risk factors in stroke populations.

Plasma Brain Natriuretic Peptide Can be a Biological Marker to Distinguish Cardioembolic Stroke from Other Stroke Types in Acute Ischemic Stroke

Plasma brain natriuretic peptide (BNP) is used as a marker of congestive heart failure. Moreover, plasma BNP levels are increased in patients with acute ischemic stroke, in particular, cardioembolic stroke. We investigated whether the plasma BNP level can also be used as a biological marker to differentiate specific stroke subtype, in particular cardioembolic stroke from the other ischemic stroke subtypes. Consecutive patients (total 200; 124 males, 76 females; mean age, 71.4 years) with acute ischemic stroke within 24 hours of onset were prospectively enrolled. We measured plasma BNP on admission. Patients were divided into four groups according to the TOAST classification: large-vessel disease (LVD), cardioembolism (CE), small-vessel disease (SVD), and other stroke. Correlation between plasma BNP level and stroke subtype was then examined. Cardioembolism (41%) was the most frequent stroke subtype, followed by other stroke (34%), SVD (16%), and LVD (9%). Age, female, atrial fibrillation, NIHSS score > or = 7 on admission and mRS score > or = 3 at discharge were significantly higher in CE than in the other stroke subtypes. The mean plasma BNP level of the CE group was significantly higher than that of the other 3 subtypes (409.6 pg/mL for CE, 94.0 pg/mL for LVD, 37.4 pg/mL for SVD, and 156.9 pg/mL for others, p<0.001). The optimal cut-off concentration, sensitivity, and specificity of plasma BNP levels to distinguish CE from other stroke subtypes were 140.0 pg/mL, 80.5% and 80.5%, respectively. Plasma BNP level is significantly higher in CE patients than in other stroke subtypes, and thus physicians should strongly consider CE when the plasma BNP level is over 140.0 pg/mL in patients with acute ischemic stroke.

A-G-4G haplotype ofPAI-1gene polymorphisms −844 G/A,HindIIIG/C, and −675 4G/5G is associated with increased risk of ischemic stroke caused by small vessel disease

Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (-844 G/A, -675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of -844 G/A, -675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke.

Retinal Microvascular Signs: A Key to Understanding the Underlying Pathophysiology of Different Stroke Subtypes?

The heterogeneity of the pathology of stroke has been a major difficulty in assessing new treatments for acute stroke, and contributes to the complexity of stroke medicine. Some underlying mechanisms are poorly understood, such as small vessel (lacunar) disease. New technology such as advanced brain imaging has transformed our knowledge of large vessel disease and we suggest that other new technology such as detailed analysis of retinal vessels may provide new insights into the pathology of small vessel (lacunar) stroke disease. We hypothesise that retinal microvascular signs differ by pathological stroke subtype, and we plan to test this hypothesis in over 1000 acute stroke patients. Eligible patients undergo a standardised neurological assessment followed by digital retinal photography. At a consensus meeting, an anatomical and aetiological classification is determined. Retinal photographs will be assessed qualitatively (e.g. retinal emboli, arteriovenous nicking) and quantitatively (arteriolar/venule ratio). Six-month vascular event rates together with disability and vital status are collected. Retinal vessel appearances may provide a 'window' to the brain and help determine the important underlying pathophysiological mechanisms of small vessel disease stroke.

Oxidative Stress and Total Antioxidant Capacity in Diabetic and Nondiabetic Acute Ischemic Stroke Patients

Free radical formation is the pivotal mechanism of neuronal injury of ischemic and reperfused brain tissue. In healthy individuals, antioxidant activity counterbalances free radical production, but in the case of ischemia, the balance between reactive oxygen species and antioxidant activity is shifted toward free radicals, causing oxidative stress. The aim of this study is to assess total antioxidant capacity (TAC) and oxidative stress in diabetic and nondiabetic acute stroke patients with 2 different stroke subtypes: large and small vessel disease stroke. Sixty-five acute ischemic stroke patients (29 diabetic and 36 nondiabetic) and 20 age-matched healthy control subjects were recruited in the study. Plasma TAC and nitric oxide (NO) metabolite levels (nitrite and nitrate) were measured by enzyme-linked immunosorbent assay. The subtypes of stroke were defined according to Trial of Org 10172 in Acute Stroke Treatment criteria. The main findings of this study are that the TAC and NO levels were significantly higher in diabetic acute stroke patients than in nondiabetic patients and control cases (P < .001 and P < .001, respectively). The TAC and NO levels were higher also in nondiabetic stroke patients than in controls, but the difference did not reach any significance. No difference was found between NO and TAC levels in large and small vessel stroke subtypes of diabetic and nondiabetic patients. The authors conclude that oxidative stress and counterbalancing antioxidant capacity are more pronounced in diabetic acute stroke patients than in nondiabetic acute stroke patients.

The Roles of Oxidized Low-Density Lipoprotein and Interleukin-6 Levels in Acute Atherothrombotic and Lacunar Ischemic Stroke

The role of circulating, oxidized low-density lipoprotein and interleukin-6 levels in acute ischemic stroke considering the primary-vessel disease was investigated. The study consisted of 28 patients with acute ischemic stroke and 23 control subjects. Patients were subdivided into large-vessel (n = 12) and small-vessel (n =16) disease stroke groups according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The means of oxidized low-density lipoprotein and interleukin-6 levels of patients with acute ischemic stroke were higher than controls (P < .01, P < .05). Mean oxidized low-density lipoprotein level was higher in the large-vessel disease group than in the small-vessel disease group (P < .01). The mean of inteleukin-6 levels was higher in the small-vessel disease group (P < .01). The results of the present study showed that oxidative stress promotes large-vessel disease rather than small-vessel disease stroke, and inflammation may play important an role in the development of small-vessel disease stroke.

Increased levels of elastin-derived peptides in cerebrospinal fluid of patients with lacunar stroke

Objective To investigate whether elastin-derived peptides (EDP) are detectable in the cerebrospinal fluid (CSF) of healthy controls and of patients with acute brain ischemia and if so to assess possible trends in EDP levels in different groups of ischemic stroke patients (small-vessel disease vs. other ischemic strokes; first-ever vs. recurrent stroke). Patients and methods Levels of EDP were determined by ELISA in blood sera and CSF of 80 patients with acute ischemic stroke (mean age 61.5 ± 10.8; age range 47–70; 22 women) and in 15 healthy age- and sex-matched controls (mean age 57.3 ± 13.4; age range 50–65). The patients were divided into a group with first ever lacunar stroke (27); first ever non-lacunar ischemic stroke (27) and recurrent stroke (26). EDP were measured early (mean 7 days, range 1–15) after stroke onset. Results Serum EDP levels were mildly higher in recurrent strokes as compared to first ever lacunar lesion and controls. However, in the CSF the concentrations of EDP in stroke patients were strongly elevated (from 2 up to 30 times depending on subgroup) as compared with healthy subjects. The highest level of EDP in CSF and in the serum was found in recurrent strokes. Subgroup analysis revealed a trend for significantly higher EDP concentrations in CSF in lacunar and recurrent stroke as compared with non-lacunar. Conclusions This study is the first application of elastin peptide measurement to human CSF and stroke patients. The increased levels of EDP were detected in CSF of patients with lacunar and recurrent strokes.

Need for extensive diagnostic work-up for patients with lacunar stroke

Small-vessel disease is the most frequent cause of lacunar stroke. The aims of this study were to evaluate: 1) alternative causes of lacunar stroke other than small-vessel disease; 2) functional outcome of lacunar strokes due to small vessel disease compared to lacunar strokes due to alternative causes. Consecutive patients with first-ever ischemic lacunar stroke were prospectively followed-up for at least 3 months. At discharge patients were divided into 2 groups: lacunar stroke due to small vessel disease (L-SVD) and lacunar stroke due to possible other etiologies (L-non SVD) (e. g. cardioembolism, atherosclerosis or other causes). Main outcome measures were the combined end point of death or disability (mRS >or= 3) and recurrent stroke at the end of follow-up. 535 patients with acute stroke were seen during the study period. Out of these, 196 patients (126 males) with a mean age of 71.6 years (SD = 10) had lacunar stroke. L-SVD was seen in 142 patients (72.4 %) and L-nonSVD in 54 patients (27.6 %). After 16.4 months, 12 patients had died (6.2%; annual mortality rate 4.4 %), 63 were disabled (32.5 %) and 27 had stroke recurrence (13.9%; annual recurrence rate 9.9 %). Forty-nine patients with L-SVD (34.7 %) and 26 with L-nonSVD (49%) had died or become disabled. Sixteen patients with L-SVD (11.3 %) and 11 with L-nonSVD (20.4 %) had stroke recurrence. On multivariate analysis, L-nonSVD (OR = 2.87, 95% CI 1.08-7.65; p = 0.034) and age (OR = 1.07, 95 % CI 1.02-1.12; p = 0.01) were associated to more severe outcome. L-nonSVD was independently associated with recurrence (OR = 5.03, 95% CI 1.54-16.44; p = 0.006). Twenty-seven percent of patients with lacunar stroke have causes other than small vessel disease. These patients have a severe outcome in terms of recurrence,mortality or disability. These findings support the need for a comprehensive diagnostic work-up for patients with lacunar stroke.

Differences in Stroke Subtypes Between Black and White Patients With Stroke

Determining whether the distribution of stroke subtypes differs between ethnic groups is important in understanding the mechanisms of the increased stroke incidence in black patients. In this study, 600 black and 600 white patients with stroke were prospectively and consecutively recruited to determine differences in stroke subtypes. The pathophysiological Trial of Org 10172 (TOAST) classification was used and compared with a clinical (Oxfordshire Community Stroke Project) subtype classification. Stroke subtypes were determined by one investigator by review of original imaging. Black patients with stroke were significantly younger and had higher prevalences of hypertension, diabetes, and obesity. They were less likely to be smokers and had lower prevalences of myocardial infarction and atrial fibrillation. In the black patients, 33% of stroke was due to cerebral small vessel disease compared with 14% in the white stroke cohort (odds ratio, 2.94; 95% confidence interval, 1.97 to 4.39; P<0.001, controlling for age, gender, cardiovascular risk factors, and social class). The black stroke cohort had less large vessel atherosclerosis (odds ratio, 0.49; 95% confidence interval, 0.29 to 0.82; P=0.007) and cardioembolic disease (odds ratio, 0.54; 95% confidence interval, 0.37 to 0.80; P=0.002). Using a classification based on clinical syndrome alone gave a higher estimate of the frequency of small vessel disease stroke, particularly in white patients. A relative excess of small vessel disease was observed in black patients with stroke compared with an excess of extracranial atherosclerosis and cardioembolic stroke in white patients with stroke that was independent of conventional risk factors and social class. Whether these excesses are due to differences in genetic susceptibility or as-yet undetermined differences in environmental risk remains to be determined.

Stroke presentation in Type 2 diabetes and the metabolic syndrome

Introduction The metabolic syndrome (MetS) is associated with macrovascular disease and an altered pattern of cerebrovascular disease. We investigated stroke subtype presentation in Type 2 diabetic (T2D) patients, and analysed patients with and without the MetS. Methods We performed a retrospective analysis of 243 T2D patients with first presentation of stroke from our Diabetes Centre database. The MetS was diagnosed in patients with T2D and two or more additional risk factors (obesity, low HDL cholesterol, elevated triglycerides or hypertension). We analysed the clinical stroke subtype presentation, using the Oxford classification of stroke, into cortical and lacunar (small vessel disease) stroke. Results The MetS was diagnosed in 151 T2D patients (62%), with 86 male and 65 female patients (age: 71.8 ± 9.7). Comparing the MetS and non-MetS groups, the distribution of stroke subtypes adjusted for age and sex were: cortical stroke (13.2% versus 15.2%; P = 0.56), lacunar stroke (43.7% versus 43.5%; P = 0.87) and TIA (38.4% versus 39.1%; P = 0.98). Lacunar stroke incidence was significantly higher compared to cortical stroke in both groups ( P < 0.001). Conclusion In this study of T2D patients, lacunar stroke (small vessel disease) was the most common stroke subtype in both patients with and without the MetS.

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke in a Polish Population

Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

Advances in Vascular Cognitive Impairment 2006

Vascular cognitive impairment is common and represents a spectrum of cognitive dysfunction associated with stroke and cardiovascular risk factors which may be slight, moderate or severe.1 Recently and as a major advance, the National Institute of Neurological Disorders and Stroke—Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards Working Group published clinical and research standards for the description and study of vascular cognitive impairment.2 In this update we report advances in vascular cognitive impairment in the following areas: clinical trials and treatment, new risk factors, white matter disease, and genetics. Cardiovascular risk factors such as blood pressure elevation and hyperglycemia are prime targets for clinical trial study because they are believed to cause negative effects on brain structure and cognitive function and may even influence risk of Alzheimer disease (AD).3 Results of recently published observational epidemiological studies have fueled controversy in relation to the role of blood pressure on cognition because some studies such as the Honolulu Asia Aging Study4 and Cache County Study5 suggest that antihypertensive therapy may reduce risk of dementia and cognitive decline or reduce incidence of AD, respectively, whereas the Religious Orders Study6 did not find an association between blood pressure and risk of AD or cognitive decline. Meta-analysis of patients with cardiovascular and/or cerebrovascular disease who received blood pressure-lowering treatment show a trend toward prevention of dementia and/or cognitive decline;7 however, a systematic analysis of 3 studies comprising 12 091 patients with hypertension who were treated with either medication or lifestyle strategies for at least 6 months show no evidence that blood pressure-lowering prevents dementia or cognitive impairment.8 Lack of definitive results in some of these trials may be explained by insufficient power to detect treatment effects, measurement error in cognitive end points, variation in treatment effects between …

ACE I/D polymorphism in different etiologies of ischemic stroke

Data concerning an association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and ischemic stroke (IS) remain inconsistent. Results of some studies suggest that DD genotype may be a risk factor for small vessel disease (SVD) stroke. Here, we investigated whether this polymorphism is associated with IS of different etiologies in a Polish population. Ischemic stroke etiology was established according to the TOAST criteria. We studied 92 stroke patients with large vessel disease and their 184 matched controls; 96 stroke patients with SVD and 192 controls; 180 patients with cardioembolic stroke (CE) and 180 controls. ACE I/D polymorphism was determined using the polymerase chain reaction method. The distribution of ACE genotypes and alleles was essentially the same in all analyzed IS subtypes and their matched controls. We failed to find an association between ACE polymorphism and etiological subtypes of IS in a Polish population.

Detection of asymptomatic cerebral microbleeds on T2*-weighted gradient-echo MRI: A comparative study at 1.5 and 3 Tesla

Purpose: Cerebral microbleeds (CMBs) are frequently associated with small vessel disease, intracerebral haemorrhage, hypertension and lacunar stroke. They are mainly located in the deep and subcortical white matter. Gradient echo T2*-weighted MRI (T2*MRI) has a high sensitivity in detecting CMBs, due to its sensitivity to iron-induced susceptibility changes. On these images hemosiderin deposits in the perivascular space appear as small dot-like hypointense lesions. However, the magnitude of iron-induced susceptibility changes increases with the field strength, which should lead to a higher sensitivity for the detection of CMBs at 3.0 T as compared to 1.5 T. To test these hypotheses, we examined individuals with documented CBMs at 1.5 and 3.0 T.

Role of COL4A1 in Small-Vessel Disease and Hemorrhagic Stroke

Small-vessel diseases of the brain underlie 20 to 30 percent of ischemic strokes and a larger proportion of intracerebral hemorrhages. In this report, we show that a mutation in the mouse Col4a1 gene, encoding procollagen type IV alpha1, predisposes both newborn and adult mice to intracerebral hemorrhage. Surgical delivery of mutant mice alleviated birth-associated trauma and hemorrhage. We identified a COL4A1 mutation in a human family with small-vessel disease. We concluded that mutation of COL4A1 may cause a spectrum of cerebrovascular phenotypes and that persons with COL4A1 mutations may be predisposed to hemorrhage, especially after environmental stress.

Detection of asymptomatic cerebral microbleeds on T2*-weighted gradient-echo MRI: A comparative study at 1.5 and 3 Tesla

Purpose: Cerebral microbleeds (CMBs) are frequently associated with small vessel disease, intracerebral haemorrhage, hypertension and lacunar stroke. They are mainly located in the deep and subcortical white matter. Gradient echo T2*-weighted MRI (T2*MRI) has a high sensitivity in detecting CMBs, due to its sensitivity to iron-induced susceptibility changes. On these images hemosiderin deposits in the perivascular space appear as small dot-like hypointense lesions. However, the magnitude of iron-induced susceptibility changes increases with the field strength, which should lead to a higher sensitivity for the detection of CMBs at 3.0 T as compared to 1.5 T. To test these hypotheses, we examined individuals with documented CBMs at 1.5 and 3.0 T.

Interleukin 1 Beta Polymorphism (–511) and Risk of Stroke due to Small Vessel Disease

Background: Interleukin 1 (IL-1) is a proinflammatory cytokine involved in atherogenesis and thrombosis. The aim of this study was to investigate the association between the IL-1β gene polymorphism (–511) and the risk of large vessel disease (LVD) stroke, small vessel disease (SVD) stroke and cardioembolic (CE) stroke. Methods: We genotyped 115 patients with LVD stroke and 194 matched controls, 122 patients with SVD stroke and 227 controls and 221 patients with CE stroke and 219 controls. The IL-1β polymorphism was analyzed by a polymerase chain reaction followed by a restriction enzyme digestion. Results: The allele T distribution did not change significantly between patients with LVD stroke and their controls nor between patients with CE stroke and their controls. The frequency of the T allele was higher in patients with SVD stroke than in the control group (37.7 vs. 30.4%, p = 0.05). After adjustment for vascular risk factor, the TT genotype was an independent risk factor for SVD stroke (OR: 2.40, 95% CI: 1.17–4.94). Conclusions: The TT genotype of the IL-1β gene may be associated with an increased risk of SVD stroke.

Endothelial Progenitor Cells, Neointimal Hyperplasia, and Hemodialysis Vascular Access Dysfunction

Vascular stenosis as a result of neointimal hyperplasia is a major clinical problem that has an impact on multiple and diverse disciplines, including cardiology (coronary restenosis), cardiothoracic and vascular surgery (saphenous vein and polytetrafluoroethylene [PTFE] graft failure), neurology (carotid stenosis), nephrology (dialysis access dysfunction), and transplant medicine (chronic allograft rejection in hearts and kidneys). The traditional response to injury hypothesis on the pathogenesis of neointimal hyperplasia focuses on the migration of medial smooth muscle cells from the media into the intima.1 Recently, there has been a great deal of excitement about the role of circulating smooth muscle progenitor cells in the pathogenesis of neointimal hyperplasia. These cells have been identified in a variety of experimental models of vascular injury,2 and interventions that reduce the number of these cells can attenuate neointimal hyperplasia. In marked contrast to the deleterious effects of smooth muscle progenitor cells on neointimal hyperplasia, circulating endothelial progenitor cells (EPCs) are believed to play an important role in vascular repair and in the inhibition of neointimal hyperplasia.3 See p 12 In this issue of Circulation , Rotmans and colleagues have attempted to achieve the “holy grail” for a vascular access procedure: rapid and complete endothelialization.4 Their experiments are based on a newly developed technique that can coat the surface of stent and graft material with antibodies against CD34 (Orbus Medical Technologies). CD34 is a marker for hematopoietic stem cells, and previous research has demonstrated that coronary stents coated with anti-CD34 have a significant increase in endothelialization as early as 1 hour after deployment because of the binding of circulating CD34+ cells, which then differentiate into endothelial cells.5 Placement of anti-CD34–coated grafts in an arteriovenous model of PTFE graft stenosis by Rotmans et al resulted in almost complete endothelialization of the grafts (both …