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Objective Arteriovenous fistulae (AVF) placed for hemodialysis have high flow rates that can stimulate left ventricular (LV) hypertrophy. LV hypertrophy generally portends poor cardiac outcomes, yet clinical studies point to superior cardiac-specific outcomes for patients with AVF when compared with other dialysis modalities. We hypothesize that AVF induce physiologic cardiac hypertrophy with cardioprotective features. Methods We treated 9- to 11-week-old C57Bl/6 male and female mice with sham laparotomy or an aortocaval fistula via a 25G needle. Cardiac chamber size and function were assessed with serial echocardiography, and cardiac computed tomography angiography. Hearts were harvested at 5 weeks postoperatively, and the collagen content was assessed with Masson's trichrome. Bulk messenger RNA sequencing was performed from LV of sham and AVF mice at 10 days. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis (Qiagen) to identify affected pathways and predict downstream biological effects. Results Mice with AVF had similar body weight and wet lung mass, but increased cardiac mass compared with sham-operated mice. AVF increased cardiac output while preserving LV systolic and diastolic function, as well as indices of right heart function; all four cardiac chambers were enlarged, with a slight decrement in the relative LV wall thickness. Histology showed preserved collagen density within each of the four chambers without areas of fibrosis. RNA sequencing captured 19 384 genes, of which 857 were significantly differentially expressed, including transcripts from extracellular matrix-related genes, ion channels, metabolism, and cardiac fetal genes. The top upstream regulatory molecules predicted include activation of angiogenic (Vegf, Akt1), procardiomyocyte survival (Hgf, Foxm1, Erbb2, Lin9, Areg), and inflammation-related (CSF2, Tgfb1, TNF, Ifng, Ccr2, IL6) genes, as well as the inactivation of cardiomyocyte antiproliferative factors (Cdkn1a, FoxO3, α-catenin). The predicted downstream effects include a decrease in heart damage, and increased arrhythmia, angiogenesis, and cardiogenesis. There were no significant sex-dependent differences in the AVF-stimulated cardiac adaptation. Conclusions AVF stimulate adaptive cardiac hypertrophy in wild-type mice without heart failure or pathologic fibrosis. Transcriptional correlates suggest AVF-induced cardiac remodeling has some cardioprotective, although also arrhythmogenic features. (JVS–Vascular Science 2021;2:110-28.) Clinical Relevance Arteriovenous fistulae (AVF) are commonly used as access for hemodialysis in patients with end-stage renal disease. AVF induce a high-output state that is associated with long-term structural cardiac remodeling, including left ventricle hypertrophy, but this element has uncertain clinical significance. Although left ventricle hypertrophy has traditionally been associated with an increased risk of cardiovascular disease, clinical studies have suggested that cardiac-specific outcomes of patients with end-stage renal disease were better with AVF compared with other dialysis modalities. This study uses a mouse model of AVF to study the structural, functional, and molecular correlates of AVF-induced cardiac remodeling. It finds that AVF causes an adaptive cardiac hypertrophy without functional decline or fibrosis. Transcriptional correlates suggest an electrical remodeling and the upregulation of proangiogenic, procardiogenic, and prosurvival factors, implying that AVF-induced cardiac hypertrophy is potentially cardioprotective, but also arrhythmogenic.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.

Objectives: Arteriovenous fistulae (AVF) are the optimal conduit for hemodialysis access in patients with end-stage chronic kidney disease (CKD); however, AVF have high rates of failure due to aggressive neointimal hyperplasia(NIH). NIH in the CKD environment is characterized by endothelial-to-mesenchymal transition (EndMT). We hypothesized that endothelial TGF-β signaling promotes EndMT to cause AVF failure. Methods: Aortocaval AVF were created in C57BL/6J mice, with control mice having sham procedures. 3 weeks prior to AVF, CKD was created via 5/6 nephrectomy (Nx); five groups were tested, including sham, sham+5/6Nx, AVF+0/6Nx, AVF+3/6Nx, AVF+5/6Nx. Endothelial cell (EC)-and smooth muscle cell (SMC)-specific TGFβRI II knockout mice were treated with tamoxifen 2 weeks prior to AVF; Ultrasound was used to determine AVF diameter and patency at postoperative days 7, 14, and 21. AVF were harvested at days 7 or 21 and examined with histology, Immunofluorescence and Western blot. Results: There was no difference between mice treated with 0/6Nx or 3/6Nx regarding AVF diameter, AVF wall thickness and accumulation of extracellular matrix (ECM) components fibronectin, collagen1, and collagen3; however, AVF diameter was significantly decreased in mice treated with 5/6Nx compared with 0/6Nx or 3/6Nx, whereas there was increased AVF wall thickness as well as immunoreactivity of fibronectin (p=0.031), collagen1 (p=0.022), collagen3 (p=0.005), and TGF-β1 (p=0.022), compared with 0/6Nx. Endothelial cells in the AVF of mice treated with 5/6Nx had significantly increased immunoreactivity of the mesenchymal markers notch3 (p Conclusion: Both EC- and SMC-specific TGF-β signaling promote EndMT and wall thickening during venous remodeling in the CKD environment. These data suggest that the TGF-β signaling pathway may be a potential therapeutic target to prevent AVF failure.

Background: Arteriovenous fistulae (AVF) fail to mature, that is dilate and thicken, in women more than in men, leading to inferior outcomes and decreased utilization in women. As our mouse AVF model recapitulates human AVF maturation, including decreased maturation and patency in female mice, we hypothesize that sex hormones mediate sex differences during AVF maturation. Methods: C57Bl/6 mice (9-11 months) were treated with sham or aortocaval AVF surgery; some were pretreated with gonadectomy 1 week prior to surgery. AVF diameter was measured via ultrasound (days 0-21). Blood was collected for FACS, and tissue examined using immunofluorescence or ELISA (days 3,7); wall thickness was assessed using histology (day 21). Results: At baseline, female and male mice had similar inferior vena cava (IVC) diameter (p=0.611) and wall thickness (p=0.491). After AVF creation, female mice had increased normalized IVC diameter (p=0.0012), flow velocity (p=0.0013), and shear stress (p=0.002; days 3-21; n=10); however, there was no difference in wall thickness (female, 15.8±0.2 um; male, 12.4±2.3 um; p=0.638; n=10). There were also increased circulating CD11b+ macrophages in female compared with male mice (31.8 ± 4.0% vs 18.7 ± 1.9%; p=0.001; day 3; n=22) and CD4+ T cells (57.9 ± 2.9% vs 34.5 ± 6.1%, p=0.0001). In the AVF wall there were increased CD45+ cells on immunofluorescence in females (22.5 ± 1.5 cells/hpf vs 13 ± 2 cells/hpf, p=0.063; day 3; n=4) as well as increased IL-10 immunoreactivity (3.98 ± 0.44 ng/ug vs 2.49 ± 0.47 ng/ug; p=0.076). In mice with gonadectomy, baseline IVC diameter, velocity, and shear stress were similar between female and male mice. After gonadectomy, male mice had increased AVF wall thickness than intact males (24.2 ± 1.6 um vs 12.4 ± 2.3; p=0.014); conversely, female mice had decreased thickness than intact females (6.1 ± 0.6 um vs 15.8 ± 0.2; p=0.005). There was loss of differences among circulating immune cells after gonadectomy (CD11b, p=0.0882; CD4, p=0.7095). Conclusions: Sex differences in hemodynamics and inflammation are present during venous remodeling, whereas these differences disappear after gonadectomy. Sex hormones mediate AVF maturation and suggest that hormone receptor signaling may be a target to improve AVF maturation.

Simple renal cysts (SRC) are associated with the development of abdominal aortic aneurysms (AAA). We hypothesized that patients with AAA and SRC have increased arterial stiffness (AS) compared with patients without SRC . Patients (n=223) with an infrarenal AAA undergoing pulse wave analysis were recruited. Brachial-ankle pulse wave velocity (PWV) was measured (automated oscillometric method) as an index of AS. Participants were categorized into those with increased AS and those with normal/borderline AS (threshold: 1800 cm/s); 134 patients (60.1%) had increased AS and 89 (39.9%) patients had normal/borderline AS. Multivariable analyses showed that age ≥75 years (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.51–5.72; P=.002), systolic blood pressure ≥140 mmHg (OR, 5.05; 95% CI, 2.35–10.83; P

© The Author(s) 2022. Sage Publications, Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

The recommendations of international guidelines for the management of asymptomatic carotid stenosis (ACS) often vary considerably and extend from a conservative approach with risk factor modification and best medical treatment (BMT) alone, to a more aggressive approach with a carotid intervention plus BMT. The aim of the current multispecialty position statement was to reconcile the conflicting views on the topic. A literature review was performed with a focus on data from recent studies. Several clinical and imaging high-risk features have been identified that are associated with an increased long-term ipsilateral ischemic stroke risk in patients with ACS. Such high-risk clinical/imaging features include intraplaque hemorrhage, impaired cerebrovascular reserve, carotid plaque echolucency/ulceration/ neovascularization, a lipid-rich necrotic core, a thin or ruptured fibrous cap, silent brain infarction, a contralateral transient ischemic attack/stroke episode, male patients

Balloon angioplasty, stent implantation, and application of an arterial clamp during surgery can induce artery injury such as elastin breaks and endothelium injury, but there is little research focused on the injury induced by these therapeutic manipulations. We established a simple and reproducible small animal aortic injury model and examined intramural injection as a potential therapeutic method to alleviate injury.The abdominal aorta of male Sprague Dawley (SD) rats or C57BL/6 J mice was clamped sequentially throughout its length. Transforming growth factor β1 (TGFβ1), SB431542, lipopolysaccharide (LPS), Necrostatin-1 (Nec-1), rapamycin, or MHY1485 contained in Pluronic gel was injected intramurally at day 0 or day 7. Animals were fed with chow containing 0.25% beta-aminopropionitrile (BAPN) to evaluate the influence of BAPN. All samples were harvested and examined by immunohistochemistry and immunofluorescence.The clamped rat aorta showed luminal dilation, elastin fiber breaks, neointimal hyperplasia, and dissection (days 0-90). Intramural injection of TGFβ1, rapamycin and Nec-1 showed a protective effect on the injured aorta, whereas SB431542, MHY1485 and LPS showed more severe wall damage. The aortic lumen in rats fed with BAPN was significantly larger than in control rats (day 7). Mouse aorta showed similar injury with neointimal hyperplasia and elastin fiber breaks.The rodent arterial injury model is reproducible and may mimic early changes of arterial injury. The model accommodates intramural injection of different drugs that may show mechanisms of arterial injury. Although this is a preliminary animal model, the intramural injection method may have potential clinical application in the future.

Reinterventions after lower extremity revascularization (LER) are common. Current outcome measures assessing durability of revascularization rely on freedom from reintervention but do not account for the frequency of repeated LER. The aim of this study is to compare the reintervention index, defined as the mean number of repeat LER, after open and endovascular revascularization. We hypothesized that endovascular procedures have reduced durability and increased frequency of reinterventions.A retrospective review of the charts of consecutive patients undergoing LER for peripheral artery disease (PAD) in 2013-2014 by multiple specialties in a tertiary care center was performed. Patients were divided into open and endovascular groups based on the first LER procedure performed during the study period. Patient characteristics and outcomes were compared between the 2 groups. Multivariable regression was performed to determine factors associated with reintervention.There were 367 patients (Endo = 316, Open = 51). A total of 211 patients underwent 497 reinterventions (reintervention rate = 57.5%, reintervention index = 2.35 ± 2.02 procedures [range 1-11]). Patients in the open group were more likely to be smokers (P = 0.018) and to have prior open LER (P = 0.003), while patients in the endovascular group were older (P 0.001) and more likely to have cardiovascular comorbidities. On follow-up, there was no difference in overall or ipsilateral reintervention rates or reintervention indices between endovascular and open LER. Major amputation was significantly higher after open LER (19.61% vs. 8.54%, P = 0.013) but there was no difference in survival (P = 0.448). Multivariable analysis did not show a significant relationship between type of procedure and reintervention.The reintervention index provides a measure to assess the frequency of repeat LER. Patients with PAD, in this study, are afflicted with similar extent of reinterventions after open and endovascular LER.

Background: The eicosapentaenoic acid to arachidonic acid ratio (EPA/AA) is attracting attention as a risk factor for peripheral artery disease (PAD). However, there have been few studies investigating the relationship between the EPA/AA ratio and atherosclerotic risk factors in patients with PAD. The purpose of the present study was to analyze atherosclerotic risk factors in patients with PAD to identify those factors associated with a low EPA/AA ratio. Methods. The data of patients treated for symptomatic PAD at Tokyo Medical University Hospital and Eniwa Midorino Clinic between April 2014 and March 2018 were retrospectively analyzed. Results. A total of 149 patients were tested for blood levels of n-3 and n-6 polyunsaturated fatty acids, including EPA and AA. 73 patients had a low EPA/AA ratio (1C (HbA1C) were associated with the low EPA/AA ratio. Multivariable analysis showed that older age (odds ratio [OR], 0.34; 95% confidential interval [CI], 0.15-0.76; p = 0.008), BMI (OR, 0.87; 95% CI, 0.77-0.98; p = 0.027), smoking history (OR, 2.67; 95% CI, 1.09-6.55; p = 0.007), and HbA1C (OR, 0.46; 95% CI, 0.29-0.72; p = 0.020) were independently associated with the low EPA/AA ratio. Conclusions. The EPA/AA ratio was related to existing arteriosclerotic risk factors in patients with PAD; it was positively correlated with older age, increasing BMI, and higher HbA1C, whereas it was negatively correlated with smoking history. These results suggest that the EPA/AA ratio may be closely intertwined with other atherosclerotic risk factors and have an influence on cardiovascular health.

Loeys-Dietz syndrome (LDS) type 3 results from a SMAD3 mutation and is a phenotypically milder variant of LDS with frequent aortic, visceral, and cerebral vascular pathologies and osteoarthritis. Historically, endovascular treatment (endovascular aortic repair [EVAR]) of LDS-related aortic aneurysmal disease with traditional modular bifurcated devices has been limited owing to concerns regarding continued aortic dilation at proximal fixation sites. Furthermore, associated dissection pathology has also precluded traditional modular bifurcated EVAR owing to inadequate proximal infrarenal necks and narrow distal aortic domains leading to compromised contralateral gate opening and cannulation as well as limb flow compromise. To address these barriers to EVAR, we present our approach for the endovascular treatment of a dissecting pararenal abdominal aortic aneurysm using an anatomically fixated, bifurcated, unibody aortic stent graft in a patient with LDS-3.

Background The spiral saphenous vein graft is an excellent choice for venous reconstruction after periphery vein injury, but only few cases have been reported. We implanted a segment of a single saphenous vein into both the popliteal vein as a venous vein graft and into the popliteal artery as an arterial vein graft at the same time in a trauma patient; we then had an extraordinary opportunity to harvest and examine both patent venous and arterial vein grafts at 2 weeks after implantation. Methods A spiral saphenous vein graft was made as previously described and implanted into the popliteal vein and artery as interposition grafts; because of the patient’s serious injuries, an amputation was performed at day 18 after vascular reconstruction. The grafts were harvested, fixed, and examined using histology and immunohistochemistry. Results Both grafts were patent, and there was a larger neointimal area in the venous graft compared to the arterial graft. There were CD31- and vWF-positive cells on both neointimal endothelia, with subendothelial deposition of α-actin-, CD3-, CD45-, and CD68-positive cells. There were fewer cells in the venous graft neointima compared to the arterial graft neointima; however, there were more inflammatory cells in the neointima of the venous graft. Some of the neointimal cells were PCNA-positive, whereas very few cells were cleaved caspase-3 positive. The venous graft neointimal endothelial cells were Eph-B4 and COUP-TFII positive, while the arterial graft neointimal endothelial cells were dll-4 and Ephrin-B2 positive. Conclusions The spiral saphenous vein graft remains a reasonable choice for vessel reconstruction, especially in the presence of diameter mismatch. Both the venous and arterial grafts showed similar re-endothelialization and cellular deposition; the venous graft had more neointimal hyperplasia and inflammation. At an early time, endothelial cells showed venous identity in the venous graft, whereas endothelial cells showed arterial identity in the arterial graft. Clinical Relevance Veins can be used as venous or arterial vein grafts but venous grafts have more neointimal hyperplasia and inflammation; vein grafts acquire different vessel identity depending on the environment into which they are implanted.

Background Postcontrast acute kidney injury (PC-AKI) is a feared complication of peripheral vascular interventions (PVIs), associated with increased mortality. Whether kidney transplant recipients (KTRs) are at increased risk of PC-AKI after PVI is unknown. This study analyzes the perioperative outcomes of KTR following PVI, with emphasis on the incidence and risk factors for PC-AKI. Methods The Vascular Quality Initiative files for PVI (2010–2018) were reviewed. Patients on dialysis were excluded. PC-AKI was defined by Vascular Quality Initiative as creatinine increase ≥0.5 mg/dL or new dialysis requirement. Characteristics of KTR and patients without kidney transplant were compared, and propensity score matching used to control for differences in baseline features. Multivariable logistic regression was used to define risk factors for PC-AKI, and survival was compared using Kaplan-Meier analysis. Results A total of 58,014 procedures were analyzed, including 641 (1%) procedures for KTR. The incidence of PC-AKI in KTR was 2.8% compared with 0.9% in patients without kidney transplants. Baseline warfarin use (odds ratio [OR] = 4.7) and poor allograft function (OR = 4.0) were significantly associated with increased risk for PC-AKI in KTR. Compared with a matched group of patients without kidney transplant, KTR had similar risk of PC-AKI and were more likely to develop postop myocardial infarction (OR = 4.3) but had lower in-hospital mortality (OR = 0.22). Conclusions The incidence of PC-AKI in KTR is higher than the overall population undergoing PVI but is not elevated compared with propensity-matched patients without kidney transplant. PVI for peripheral artery disease in KTR is safe and associated with acceptable perioperative and long-term survival.

Background Seasonal variation in coronary artery disease is well described, with a peak in the winter and a trough in the summer. However, little is known about seasonal trends in hospital admission for critical limb-threatening ischemia (CLTI) and associated outcomes. Methods Patients admitted with CLTI from January 1, 2012 through August 31, 2015 were identified in the Healthcare Cost and Utilization Project's National Inpatient Sample based upon administrative claims diagnosis codes. The primary outcome was seasonal hospitalization incidence, and secondary outcomes included mortality rates and rates of in-hospital major and minor amputations among nondiabetics and diabetics. Results Of 1,276,745 hospitalizations for CLTI during the study period, 28.3% occurred in the spring, the peak admission season, and 19.1% occurred in the fall, the nadir. In-hospital mortality was highest during the winter (adjusted odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.03-1.14), and followed the highest seasonal rates of influenza in the fall; however, other important comorbidities did not differ significantly by season. For the overall cohort, there was no significant seasonal variation in rates of major or minor amputation, although seasonal rates were different according to diabetic status. Patients without diabetes had the highest odds of amputation in the spring (OR 1.07; 95% CI: 1.02-1.12), although this trend was not identified among patients with diabetes. Conclusions There is significant seasonal variability in CLTI admissions and mortality but minimal variability in amputation rates. Understanding the seasonal variation in CLTI may help to identify individuals at greatest risk for hospitalization and death through patient and provider education efforts.

As the general population ages, there will be an increasing number of vascular patients in their 90s and older. However, geriatric patients have historically been turned down for abdominal aortic aneurysm repair despite high aneurysm-related mortality in the unrepaired. Herein, we describe the perioperative considerations and the successful, uncomplicated operative course of a 100-year-old woman who underwent an elective endovascular aortic aneurysm repair for an expanding 5.3-cm abdominal aortic aneurysm. Given a suitable patient, there is acceptable risk profile of an endovascular approach, even in centenarians.

Anomalous marginal veins of the trunk or extremities are congenitally incompetent entities found in association with phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth syndromes, such as Klippel-Trenaunay syndrome and congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal deformities (CLOVES) syndrome. When present, they can be a major source of venous hypertension-related morbidity and potentially lethal thromboembolic events. Herein, we describe a rare case of an upper extremity marginal vein in a patient with CLOVES syndrome. Through a multimodal therapeutic approach, we identified a somatic PIK3CA mutation in the excised anomalous vein. This finding questions the validity of commonly employed terminology, such as persistent embryonic vein, in reference to these anomalous entities.

ObjectiveEndovascular aneurysm repair has become the primary treatment modality for ruptured infrarenal abdominal aortic aneurysm. This study examines the impact of endograft type on perioperative outcomes for ruptured infrarenal abdominal aortic aneurysm.MethodThe targeted endovascular aneurysm repair files of the American College of Surgeons National Surgical Quality Improvement Program database (2012–2017) were used. Only patients treated for ruptured infrarenal abdominal aortic aneurysm were included. All patients requiring concomitant stenting of the visceral arteries or aneurysmal iliac arteries or open abdominal surgery were excluded. The characteristics of patients treated with the different endografts and the corresponding outcomes were compared using Stata software.ResultsThere were 479 patients treated with the three most common endografts: Cook Zenith ( n = 127), Gore Excluder ( n = 239), and Medtronic Endurant ( n = 113). The number of other endografts was too small for statistical analysis. Compared to patients treated with Excluder or Endurant, the patients treated with Zenith had significantly lower body mass index ( P ConclusionsThis study highlights contemporary outcomes of endovascular aneurysm repair for ruptured infrarenal abdominal aortic aneurysm with relatively low mortality. Endograft type and anesthesia technique are modifiable factors that can potentially improve outcomes. Significant variation in the outcomes of the different endografts warrants further research.

Critical limb ischemia (CLI) is the clinical manifestation of severe peripheral artery disease presenting as rest pain (RP) and tissue loss (TL). Most studies compare CLI as a homogenous group with claudication with limited database studies specifically studying these differences. We hypothesize that CLI should be stratified into RP and TL because of significant differences in disease severity, comorbidities, and outcomes.The American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2016 was reviewed. All patients with a postoperative diagnosis of CLI undergoing femoral to popliteal bypass (FPB) with vein or graft were identified. Patients were stratified into cohorts based on International Classification of Disease (ICD)-9 or ICD-10 codes for RP or TL (gangrene or ulcer). Univariate and multivariate analyses were performed to examine 30-day mortality, morbidity, major amputation, and readmission adjusting for demographics, comorbidities, and procedural details.There were 5,304 patients. Compared to RP, patients with TL were older (P 0.0001) and more likely to be dependent (P 0.0001). TL patients were also more likely to have diabetes (P 0.0001), congestive heart failure (P 0.0001), renal failure (P = 0.004), dialysis (P 0.0001), history of wound infection (P 0.0001), and sepsis (P 0.0001). TL patients had higher American Society of Anesthesiologists class (P 0.0001), were less likely to be transferred from home (P 0.0001), and more likely to receive an FPB with vein (P = 0.03). Patients with TL had worse perioperative outcomes compared with RP in terms of pneumonia (P = 0.004), unplanned intubation (P = 0.009), cardiac arrest requiring cardiopulmonary resuscitation (P = 0.003), bleeding requiring transfusions (P 0.0001), sepsis (P 0.0001), septic shock (P = 0.02), and reoperation (P 0.0001). TL was associated with significantly higher 30-day morbidity (P 0.0001), 30-day mortality (P 0.0001), major amputation (P = 0.0004), and readmission rates (P = 0.005). Patients with TL compared with those with RP also had longer hospital stays (P 0.0001) and days between operation to discharge (P 0.0001). TL was independently associated with increased 30-day morbidity (OR: 1.16 [1.00-1.35]) and major amputation (OR: 2.48 [1.29-4.76]) compared with RP.Patients with RP and TL have drastic differences that impact perioperative mortality and readmissions. TL is an independent predictor of 30-day morbidity and major amputation. The stratification of CLI into RP and TL can provide insight into variations in outcomes and provide a means to quantify the risks associated with the 2 manifestations of the disease.

Stenosis due to neointimal hyperplasia (NIH) is among the major causes of peripheral graft failure. Its link to abnormal hemodynamics in the graft is complex, and isolated use of hemodynamic markers is insufficient to fully capture its progression. Here, a computational model of NIH growth is presented, establishing a link between computational fluid dynamics simulations of flow in the lumen and a biochemical model representing NIH growth mechanisms inside the vessel wall. For all three patients analyzed, NIH at proximal and distal anastomoses was simulated by the model, with values of stenosis comparable to the computed tomography scans.

Symptomatic carotid artery disease caused by hyoid bone compression is rare, although scant reports describe cerebrovascular events due to this mechanical interference leading to entrapment, embolism, dissection, atherosclerotic stenosis, and pseudoaneurysm formation. This report describes a patient presenting with left-sided paresis and paresthesia who was found to have focal right carotid stenosis secondary to impingement of the carotid bulb by an elongated hyoid bone. Whereas previous cases describe hyoid bone resection, we describe successful management with endarterectomy and carotid mobilization without hyoid resection, with long-term follow-up demonstrating a widely patent carotid system without recurrent impingement. Keywords: Hyoid bone, Carotid artery, Carotid stenosis, Atherosclerosis, Cerebral infarction

Aim: To assess the potential of human induced pluripotent stem cell-derived smooth muscle cells (hiPSC-SMC) to accelerate diabetic wound healing. Methods: hiPSC-SMC were embedded in 3D collagen scaffolds and cultured in vitro for 72 h; scaffolds were then applied to diabetic, nude mouse, splinted back wounds to assess in vivo healing. Cultured medium after scaffold incubation was collected and analyzed for expression of pro-angiogenic cytokines. Results: hiPSC-SMC secrete increased concentration of pro-angiogenic cytokines, compared with murine adipose derived stem cells. Delivery of hiPSC-SMC-containing collagen scaffolds accelerates diabetic wound healing and is associated with an increased number of total and M2 type macrophages. Conclusion: hiPSC-SMC promote angiogenesis and accelerate diabetic wound healing, making them a promising new candidate for treatment of diabetic wounds., Graphical abstract

Background Critical limb ischemia (CLI) involving infrapopliteal arterial atherosclerosis and tissue loss remains a formidable clinical scenario with significant morbidity and mortality. Despite level IA evidence, tibial revascularization with coronary drug-eluting stents (DES) remains a seldom-used technique in the United States due, in part, to lack of a Food and Drug Administration–approved indication and dedicated stent technology for infrapopliteal application. Furthermore, follow-up data beyond 1 year remain scarce, and further evidence for improvement in clinical outcomes using this technique is needed. Herein, we present our multi-institutional experience with endovascular revascularization of patients with CLI and tissue loss using coronary DES for infrapopliteal lesions of appropriate dimensions and the Wound, Ischemia, and foot Infection (WIfI) score as supportive evidence for improvement in clinical outcomes. Methods In this retrospective study, 40 sequential tibial revascularization procedures performed in 32 patients with CLI were reviewed. Outcomes including changes in WIfI scores, patency rates, freedom from major amputation, target lesion recurrence, and all-cause mortality were analyzed. Average follow-up duration was 19.3 months (interquartile range: 7–27.1 months). Results Freedom from major amputation was 88.6%. One-year primary patency was 90.3%. Mean ankle-brachial indices increased after revascularization (0.57 ± 0.26 to 0.97 ± 0.26; P = 0.03). All components of the WIfI score significantly improved after revascularization (W: 1.9 to 1.1, P = 0.03; I: 2.0 to 0.6, P = 0.001; and fI: 1.5 to 0.8, P = 0.01). WIfI risk of major amputation score before revascularization was 3.58 ± 0.75 (high risk), which was reduced to 2.04 ± 1.31 (low risk; P Conclusions Coronary DES continue to demonstrate promising primary patency and limb salvage rates in appropriately selected patients undergoing multilevel endovascular revascularization for CLI and tissue loss. In addition to its value as a predictor for major amputation and revascularization benefit, the WIfI score can also serve as a multicomponent tool for objective assessment of outcomes after revascularization.

Objective: The arteriovenous fistula (AVF) is the preferred method of dialysis access because of its proven superior long-term outcomes. However, women have lower rates of AVF patency and utilization than men. We used a novel mouse AVF model that recapitulates human AVF maturation to determine whether there are differences in AVF patency in female and male mice. Methods: Aortocaval fistulas were created in female and male C57BL/6 mice (9-10 weeks). At days 0, 3, 7, and 21, infrarenal inferior vena cava (IVC) and aortic diameters and flow velocity were monitored by Doppler ultrasound and used to calculate the vessel diameter, blood flow, and shear stress. AVF were harvested, and expression of proteins was examined by proteomic analysis and immunofluorescence and of messenger RNA by quantitative polymerase chain reaction analysis. Results: At baseline, female mice weighed less and had lower IVC velocity and smaller magnitudes of shear stress, but there was no significant difference in IVC diameter and thickness. After AVF creation, both female and male mice had similar IVC dilation and thickening with no significant differences in IVC wall thickness at day 21. However, female mice had diminished AVF patency by day 42 (25.7% vs 64.3%; P = .039). During fistula remodeling, female mice had lower IVC mean velocity and shear stress magnitude and increased spectral broadening (days 0-21). Messenger RNA and protein expression of Krüppel-like factor 2, endothelial nitric oxide synthase, and vascular cell adhesion molecule 1 was similar at baseline in female and male mice but increased in the AVF only in male mice but not in female mice (day 21). Proteomic analysis of female and male mice detected 56 proteins expressed at significantly higher levels in the IVC of female mice and 67 proteins expressed at significantly higher levels in the IVC of male mice (day 7); function-specific analysis showed that the IVC of male mice overexpressed proteins that belong to pathways implicated in the regulation of vascular function, thrombosis, response to flow, and vascular remodeling. Conclusions: AVF in female mice have diminished patency, preceded by lower velocity, reduced magnitudes of shear stress, and less laminar flow during remodeling. There is also sex-specific differential expression of proteins involved in thrombosis, response to laminar flow, inflammation, and proliferation. These findings suggest that hemodynamic changes during fistula maturation may play an important role underlying the diminished rates of AVF utilization in women. : Clinical Relevance: Women have lower rates of arteriovenous fistula (AVF) utilization than men. Using a mouse AVF model that recapitulates human AVF maturation, we show that female mice have similar AVF remodeling but diminished patency. AVF remodeling in female mice is associated with reduced shear stress and laminar flow; lack of increased transcription and translation of several anti-inflammatory, antiproliferative, and laminar flow response proteins (endothelial nitric oxide synthase, Krüppel-like factor 2, and vascular cell adhesion molecule 1); and different patterns of expression of pathways that regulate thrombosis and venous remodeling. Identifying downstream targets involved in these mechanisms may improve AVF outcomes in female patients.

To investigate cognitive changes after carotid revascularization in elderly patients with asymptomatic carotid artery stenosis. We also compared cognitive outcomes of carotid endarterectomy CEA with stenting in asymptomatic patients.From April 2019 to December 2019, patients with ≥70% asymptomatic carotid stenosis who were treated with CEA or CAS, were recruited for this study. The Montreal cognitive assessment (MoCA) instrument was used to evaluate cognitive function preoperatively and postoperatively at 3, 6, and 12 months. The incidence of ipsilateral ischemic cerebrovascular events and restenosis were analyzed within 12 months.In 50 patients treated with CEA or carotid artery stenting CAS, baseline cognitive function was not different between CEA and CAS groups (P 0.05). There was no difference in the incidence of ipsilateral ischemic cerebrovascular events and restenosis within the first 12 months between the two groups. There was a significant improvement in the total MoCA score, scores of attention, and delayed recall at 3, 6 and 12 months after revascularization compared with scores at baseline (all P 0.001). At 12 months, scores of cube copying and clock drawing were significantly improved (P = 0.014, P = 0.020). The clock drawing score was improved at 12 months after CAS compared with CEA (P = 0.040).Carotid revascularization has a beneficial effect on cognition in asymptomatic patients within 12 months of the procedure. Compared with CEA, CAS show improved test scores of executive functioning by 1 year.

Background Endovascular treatment of atherosclerotic arterial disease exhibits sex differences in clinical outcomes including restenosis. However, sex-specific differences in arterial identity during arterial remodeling have not been described. We hypothesized that sex differences in expression of the arterial determinant erythropoietin-producing hepatocellular receptor interacting protein (Ephrin)-B2 occur during neointimal proliferation and arterial remodeling. Methods and results Carotid balloon injury was performed in female and male Sprague–Dawley rats without or 14 days after gonadectomy; the left common carotid artery was injured and the right carotid artery in the same animal was used as an uninjured control. Arterial hemodynamics were evaluated in vivo using ultrasonography pre-procedure and post-procedure at 7 and 14 days and wall composition examined using histology, immunofluorescence and Western blot at 14 days after balloon injury. There were no significant baseline sex differences. 14 days after balloon injury, there was decreased neointimal thickness in female rats with decreased smooth muscle cell proliferation and decreased type I and III collagen deposition, as well as decreased TNFα- or iNOS-positive CD68+ cells and increased CD206− or TGM2-positive CD68+ cells. Female rats also showed less immunoreactivity of VEGF-A, NRP1, phosphorylated EphrinB2, and increased Notch1, as well as decreased phosphorylated Akt1, p38 and ERK1/2. These differences were not present in rats pretreated with gonadectomy. Conclusions Decreased neointimal thickness in female rats after carotid balloon injury is associated with altered arterial identity that is dependent on intact sex hormones. Alteration of arterial identity may be a mechanism of sex differences in neointimal proliferation after arterial injury.

The influence of lower limb ischemia on the loss of skeletal muscle mass, which is a prerequisite for sarcopenia, remains poorly studied in patients with peripheral artery disease (PAD). We determined whether or not lower limb ischemia correlates with a loss of skeletal muscle mass in patients with PAD.The data of 101 patients (202 legs) with PAD were retrospectively analyzed. Body composition was measured using a bioelectrical impedance analysis. Based on the Asian Working Group for Sarcopenia, low muscle mass (LMM) was defined as skeletal muscle mass index (SMI)7.00 kg/mThere were significant differences in age, ankle-brachial pressure index (ABI) per patient, and the geriatric nutritional risk index (GNRI), between patients with and without LMM. Multivariable logistic regression analysis showed age (odds ratio [OR], 1.09; p = 0.009), GNRI (OR, 0.93; p = 0.003), and ABI per patient (OR, 0.02; p = 0.027) as independent risk factors for LMM.These data show a detrimental effect of lower limb ischemia on skeletal muscle mass loss, suggesting that PAD may affect the development of secondary sarcopenia.

Purpose: The factors associated with aneurysm sac shrinkage after endovascular aneurysm repair (EVAR) are not well established. As inflammation is implicated in aneurysm pathophysiology, we hypothesized that high-sensitivity C-reactive protein (hsCRP) was associated with aneurysm sac shrinkage after EVAR and compared the preoperative level of hsCRP between patients with and without postoperative aneurysm sac shrinkage after EVAR. Methods: From November 2013 to April 2019, 143 patients undergoing EVAR using Gore C3 Excluder (W. L. Gore & Associates, Inc, Flagstaff, Arizona) at our university hospital were included in this study. Aneurysm sac size was compared between that on baseline preoperative computed tomography (CT) and that on postoperative CT scans. A change in aneurysm sac size ≥5 mm was considered to be significant, whether due to enlargement or shrinkage. Results: Aneurysm sac size showed a significant decrease from 50.6 ± 9.8 mm to 47.1 ± 10.3 mm at 1 year. At 1 year postoperatively, aneurysm sac shrinkage (≥5 mm) was observed in 48 patients (34%), a stable aneurysm sac was noted in 93 patients (65%), and aneurysm sac enlargement was noted in 2 patients (1.4%). The mean preoperative hsCRP was 0.33 ± 0.54 mg/dL. Univariable analysis showed that preoperative hsCRP (p=0.029) and the presence of a renal cyst (p=0.002) were associated with aneurysm sac shrinkage. Multivariable analysis showed that preoperative hsCRP [>0.19mg/dL] (odds ratio [OR] = 0.22; 95% confidence interval [CI] = 0.05–0.96; p=0.042), and the presence of a renal cyst (OR = 0.31; 95% CI = 0.15–0.67; p=0.002) were independent risk factors for aneurysm sac shrinkage after EVAR. Conclusions: The level of preoperative hsCRP was independently associated with aneurysm sac shrinkage after EVAR in patients with abdominal aortic aneurysms. These data suggest that the high level of hsCRP can be a negative predictor for aneurysm sac shrinkage after EVAR.

Bleeding is a rare but potentially life-threatening complication of varicose veins. There is paucity of literature about patients with varicose veins that present with bleeding and the effectiveness of vein ablation as therapy to prevent recurrent bleeding. This study compares patients treated with vein ablation for bleeding varicose veins with patients treated for venous symptoms other than bleeding. We hypothesize that vein ablation is safe and effective in preventing recurrence of bleeding from varicose veins.A retrospective single-centre review of consecutive patients undergoing vein ablation using radiofrequency in an outpatient office was performed. Patients presenting with bleeding were identified. A random (3:1) group of patients undergoing vein ablation for other venous symptoms and no bleeding was selected as a comparative group (control). The medical records were reviewed for patient characteristics and outcomes. A telephone survey inquiring about intensity of symptoms on a numeric rating scale of 0 to 10 prior and after treatment as well as recurrence of bleeding was also conducted. Patient characteristics and outcomes were compared between the two groups.The incidence of patients with bleeding varicose veins was 3.6% (13/362) of all patients undergoing vein ablation at our center. A total of 26 ablations and 60 ablations were performed in patients with bleeding (n = 13) and controls (n = 39), respectively. There was no difference in age and race, but there was a trend for bleeding to occur more commonly in male patients (61.5% vs 33.3%; P = .073). Patients with bleeding from varicose veins were more likely to have congestive heart failure (P = .013) and present with more advanced venous disease based on CEAP classification (P = .005) compared with the control group. There was no difference between the 2 groups in vein closure (P = .246) or complications (P = .299) after vein ablation. With mean follow-up of 2.26 ± 1.17 years, 85% of patients (n = 11) remained free from bleeding episodes. One patient with recurrent bleeding required additional vein ablation and the second patient had a concomitant ulcer that was treated with compression therapy.Bleeding from varicose veins is rare and more common in patients with congestive heart failure. Bleeding affects patients with higher CEAP scores. Vein ablation is a safe and effective treatment to prevent the recurrence of bleeding.

Background Arterial stiffness may be the underlying cause of the divergent sac behavior after endovascular aortic repair (EVAR). We evaluated arterial stiffness using pulse wave velocity (PWV) in patients undergoing EVAR for abdominal aortic aneurysm (AAA) and demonstrated that arterial stiffness is a predictor for determining sac behavior after EVAR. Methods and results One hundred nineteen patients with infrarenal AAA undergoing EVAR between November 2013 and July 2019 were included in this study. Preoperative brachial-ankle PWV was measured using an automated oscillometric method at our vascular laboratory. PWV and other risk factors were assessed with respect to being a risk factor for sac shrinkage at 2 years postoperatively. Univariate and multivariable analyses revealed preoperative PWV (odds ratio [OR] 0.87; 95% confidence interval [CI] 0.79-0.98; p = 0.045) and the incidence of operative type II endoleak (OR 0.68; 95% CI 0.10-0.81; p = 0.048) as an independent risk factor for sac shrinkage at 2 year postoperatively. The receiver-operating characteristic curve analysis showed that the optimal cutoff value for predicting sac shrinkage was 17.79 m/s, and significantly predicted sac shrinkage. Conclusions Preoperative PWV was independently associated with sac shrinkage after EVAR, suggesting that arterial stiffness may be one of the key factors for determining sac behavior after EVAR.

Background Proteinuria and glomerular segmental fibrosis are inevitable complications of diabetic nephropathy though their mechanisms are poorly understood. Understanding the clinical characteristics and pathogenesis of proteinuria and glomerular segmental fibrosis in diabetic nephropathy is, therefore, urgently needed for patient management of this severe disease. Methods and Results Diabetes mellitus was induced in podocyte‐specific glucocorticoid receptor knockout (GR PKO ) mice and control littermates by administration of streptozotocin. Primary podocytes were isolated and subjected to analysis of Wnt signaling and fatty acid metabolism. Conditioned media from primary podocytes was transferred to glomerular endothelial cells. Histologic analysis of kidneys from diabetic GR PKO mice showed worsened fibrosis, increased collagen deposition, and glomerulomegaly indicating severe glomerular fibrosis. Higher expression of transforming growth factor‐βR1 and β‐catenin and suppressed expression of carnitine palmitoyltransferase 1A in nephrin‐positive cells were found in the kidneys of diabetic GR PKO mice. Podocytes isolated from diabetic GR PKO mice demonstrated significantly higher profibrotic gene expression and suppressed fatty acid oxidation compared with controls. Administration of a Wnt inhibitor significantly improved the fibrotic features in GR PKO mice. The glomerular endothelium of diabetic GR PKO mice demonstrated the features of endothelial‐to‐mesenchymal transition. Moreover, endothelial cells treated with conditioned media from podocytes lacking GR showed increased expression of α‐smooth muscle actin, transforming growth factor‐βR1 and β‐catenin levels. Conclusions These data demonstrate that loss of podocyte GR leads to upregulation of Wnt signaling and disruption in fatty acid metabolism. Podocyte–endothelial cell crosstalk, mediated through GR, is important for glomerular homeostasis, and its disruption likely contributes to diabetic nephropathy.

Advances in endovascular therapy have exponentially increased the number of procedures performed for peripheral artery disease, but public concerns of overuse have placed the vascular community under scrutiny. The appropriateness of care has thus become a focus of discussion within several professional societies, but literature on the topic is limited. This report presents two cases of patients with peripheral artery disease, one patient who did not need revascularization and underwent an intervention and the other who required additional intervention that was not recognized owing to an incomplete diagnostic workup. Keywords: Appropriateness of care, Peripheral arterial disease, National guidelines

Background The goals of this study were to evaluate mid-term outcome in endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) using a GORE C3 EXCLUDER and compare results between patients treated within and outside the instructions for use (IFU). Methods Over a 3-year period spanning October 2013 to September 2016, consecutive patients undergoing EVAR for AAA using the C3 EXCLUDER at Tokyo Medical University Hospital were registered on a prospectively maintained database. The data thus obtained were retrospectively analyzed. Results A total of 109 AAA patients underwent EVAR using the C3 EXCLUDER. The median follow-up duration was 729 days (interquartile range, 542–1,069 days). Technical success was achieved in 98.2% of cases. Adjunctive, unplanned proximal cuff-extender implantation was required in 8 patients (9.2%). Of the total number, 29 (24.8%) were categorized as being treated outside the IFU. No significant difference was observed in freedom from overall mortality or aneurysm-related mortality between patients treated within and outside the IFU. Freedom from reintervention tended to be lower in patients treated outside the IFU. There was aneurysm sac shrinkage (≥5 mm) in 30.3% and 39.1%; stable aneurysm sac in 69.7% and 56.3%; and aneurysm sac expansion (≥5 mm) in 0% and 4.7% of cases at 1 and 2 years, respectively. No significant difference was observed in aneurysm sac shrinkage between patients treated within and outside the IFU. Conclusions The C3 EXCLUDER showed good clinical performance and aneurysm sac shrinkage, regardless of whether the patient was treated within or outside the IFU. The results suggest, however, that in those treated outside the IFU, precise planning, careful operative procedure, and subsequent follow-up are required to obtain short-term and mid- to long-term success in EVAR for AAA using the C3 EXCLUDER.

Femoral endarterectomy with iliac stenting is a safe and effective minimally invasive alternative to aortobifemoral bypass. However, TransAtlantic Inter-Society Consensus D lesions with contiguous iliofemoral occlusion are challenging cases for hybrid repair. Herein, we present a unique approach for iliofemoral revascularization by on-table modification of self-expanding covered stents. Keywords: Aortoiliac occlusive disease, Endarterectomy, Covered stent, Hybrid vascular surgery

Objectives Despite reports of increasing use of hybrid surgery for lower extremity revascularization in Europe, little is known about the performance of hybrid procedures in the U.S. This study aims to investigate contemporary national trends in frequency and operator distribution of hybrid lower extremity revascularization and compare the perioperative outcomes of independent vascular surgeons and other surgical specialists. We hypothesized that hybrid procedures are increasingly performed, and independent vascular surgeons have superior outcomes compared to other surgical specialists. Methods The 2005–2015 American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database was used to identify patients undergoing open or hybrid lower extremity revascularization based on Current Procedural Terminology codes. Only patients treated for peripheral artery disease, based on International Classification of Diseases codes-9, were included. A trend of yearly hybrid lower extremity revascularization compared to open lower extremity revascularization was obtained. The most commonly performed hybrid procedure was identified as well as the specialties of the primary operators. Operators were categorized as “independent vascular surgeons” and “other surgeons” if the primary operator was a non-vascular surgeon or a vascular surgeon assisted by a second specialist as part of a team. Patients undergoing this hybrid lower extremity revascularization by independent vascular surgeons were selected and matched (2:1) to the patients who underwent the same procedure by other surgical specialists. Matching was based on age, gender, functional status, American Society of Anesthesiologists classification, transfer status, emergent surgery, and indication. The characteristics and perioperative outcomes of those two groups were compared. Results The overall rate of hybrid procedures increased from 4% in 2005 to 14% in 2015 ( p Conclusion Hybrid lower extremity revascularization for peripheral artery disease has been increasingly used and is performed primarily by independent vascular surgeons. Simple hybrid procedures may be performed safely by vascular surgeons as well as other trained surgical specialists.

Background Prosthetic arteriovenous grafts (AVG) continue to have a high rate of failure in clinical use, yet there is continued clinical demand for them. However, there is no small animal model of AVG to test novel tissue-engineered vascular grafts. We established a new rat arteriovenous graft model to compare the healing of decellularized carotid artery (CA) to autologous CA. Materials and methods The infrarenal vena cava and aorta of Wistar rats were exposed and dissected free below renal artery. A longitudinal 1 mm venotomy and arteriotomy were made on the anterior walls. The conduit was either autologous CA or heterologous decellularized CA; a conduit was sewn to the inferior vena cava and aorta in end-to-side fashion. Rats were sacrificed on postoperative day 21 for examination. Results All rats survived without heart failure. Conduits had 100% patency rate (day 21) in both the control and decellularized CA groups (n = 6). Both control and decellularized CA showed similar rates of reendothelialization, inflammatory cell infiltration, and cell turnover. The outflow vein beyond the autologous or decellularized conduits showed similar neointimal thickness and cell turnover. Conclusions Decellularized CA may be a viable tissue engineering graft for use as an arteriovenous graft for dialysis access. The rat aorta-vena cava graft is a useful model to test new materials including tissue-engineered grafts for use as AVG.

Background Arteries, veins, and lymphatic vessels are distinguished by structural differences that correspond to their different functions. Each of these vessels is also defined by specific molecular markers that persist throughout adult life; these markers are some of the molecular determinants that control the differentiation of embryonic undifferentiated cells into arteries, veins, or lymphatics. Methods This is a review of experimental literature. Results The Eph-B4 receptor and its ligand, ephrin-B2, are critical molecular determinants of vessel identity, arising on endothelial cells early in embryonic development. Eph-B4 and ephrin-B2 continue to be expressed on adult vessels and mark vessel identity. However, after vascular surgery, vessel identity can change and is marked by altered Eph-B4 and ephrin-B2 expression. Vein grafts show loss of venous identity, with less Eph-B4 expression. Arteriovenous fistulas show gain of dual arterial-venous identity, with both Eph-B4 and ephrin-B2 expression, and manipulation of Eph-B4 improves arteriovenous fistula patency. Patches used to close arteries and veins exhibit context-dependent gain of identity, that is, patches in the arterial environment gain arterial identity, whereas patches in the venous environment gain venous identity; these results show the importance of the host infiltrating cells in determining vascular identity after vascular surgery. Conclusions Changes in the vessel's molecular identity after vascular surgery correspond to structural changes that depend on the host's postsurgical environment. Regulation of vascular identity and the underlying molecular mechanisms may allow new therapeutic approaches to improve vascular surgical procedures.

Despite scientific advances, vascular diseases are responsible for one third of deaths. Understanding the biology of stem cells and cell therapy can mean an important advance in reducing this mortality. Apesar dos avanços científicos, as doenças vasculares são responsáveis por um terço dos óbitos. Entender a biologia das células tronco e a terapia celular pode significar importante avanço na redução desta mortalidade.