Heterogeneous gene expression during early arteriovenous fistula remodeling suggests that downregulation of metabolism predicts adaptive venous remodeling.

Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis.

Midterm outcomes of subclavian artery revascularization in the setting of thoracic endovascular aortic repair.

Objective: The outcomes of subclavian artery revascularization (SAR) have been examined extensively in the setting of atherosclerotic occlusive disease but have been poorly characterized in the setting of thoracic endovascular aortic repair (TEVAR). As trials for branched thoracic endovascular stent grafts materialize, the outcomes of the subclavian artery branched prosthesis will need to be compared with TEVAR with SAR by carotid-subclavian bypass or subclavian transposition.

Methods: A database of 1516 patients undergoing TEVAR from 2000 to 2015 was queried.

Venous Mechanical Properties After Arteriovenous Fistulae in Mice.

Background: An arteriovenous fistula (AVF) exposes the outflow vein to arterial magnitudes and frequencies of blood pressure and flow, triggering molecular pathways that result in venous remodeling and AVF maturation. It is unknown, however, how venous remodeling, that is lumen dilation and wall thickening, affects venous mechanical properties. We hypothesized that a fistula is more compliant compared with a vein because of altered contributions of collagen and elastin to the mechanical properties.

Endovascular interventions decrease length of hospitalization and are cost-effective in acute mesenteric ischemia.

Objective: Acute mesenteric ischemia (AMI) continues to be one of the most devastating diagnoses requiring emergent vascular intervention. There is a national trend toward increased use of endovascular procedures, with improved survival for the treatment of these patients. Our aim was to evaluate whether this trend has changed the treatment of AMI and the subsequent impact on length of hospitalization and hospitalization costs.

Improved mortality in treatment of patients with endovascular interventions for chronic mesenteric ischemia.

Objective: Chronic mesenteric ischemia (CMI) continues to be a devastating diagnosis. There is a national trend toward increased use of endovascular procedures with improved survival for the treatment of these patients. Our aim was to evaluate whether this trend has changed CMI patients' length of hospitalization and health care cost.

Eph-B4 regulates adaptive venous remodeling to improve arteriovenous fistula patency.

Low rates of arteriovenous fistula (AVF) maturation prevent optimal fistula use for hemodialysis; however, the mechanism of venous remodeling in the fistula environment is not well understood. We hypothesized that the embryonic venous determinant Eph-B4 mediates AVF maturation. In human AVF and a mouse aortocaval fistula model, Eph-B4 protein expression increased in the fistula vein; expression of the arterial determinant Ephrin-B2 also increased.

CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation.

Objective: Arteriovenous fistulae (AVF) remain the optimal conduit for hemodialysis access but continue to demonstrate poor patency and poor rates of maturation. We hypothesized that CD44, a widely expressed cellular adhesion molecule that serves as a major receptor for extracellular matrix components, promotes wall thickening and extracellular matrix deposition during AVF maturation.

Approach And Results: AVF were created via needle puncture in wild-type C57BL/6J and CD44 knockout mice.

Increased Oxidative Stress and Hypoxia Inducible Factor-1 Expression during Arteriovenous Fistula Maturation.

Background: The poor clinical results that are frequently reported for arteriovenous fistulae (AVF) for hemodialysis are typically due to failure of AVF maturation. We hypothesized that early AVF maturation is associated with generation of reactive oxygen species and activation of the hypoxia-inducible factor-1 (HIF-1) pathway, potentially promoting neointimal hyperplasia. We tested this hypothesis using a previously reported mouse AVF model that recapitulates human AVF maturation.

Disturbed shear stress reduces Klf2 expression in arterial-venous fistulae in vivo.

Laminar shear stress (SS) induces an antiproliferative and anti-inflammatory endothelial phenotype and increases Klf2 expression. We altered the diameter of an arteriovenous fistula (AVF) in the mouse model to determine whether increased fistula diameter produces disturbed SS in vivo and if acutely increased disturbed SS results in decreased Klf2 expression. The mouse aortocaval fistula model was performed with 22, 25, or 28 gauge needles to puncture the aorta and the inferior vena cava.

Ephrin type-B receptor 4 activation reduces neointimal hyperplasia in human saphenous vein in vitro.

Background: Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase ephrin type-B receptor 4 (Eph-B4) with its ligand ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in adult human veins is capable of phosphorylation and activation of downstream signaling pathways, as well as functional to release nitric oxide (NO) and prevent neointimal hyperplasia in vitro.

Temporal regulation of venous extracellular matrix components during arteriovenous fistula maturation.

Purpose: The venous limb of arteriovenous fistulae (AVF) adapts to the arterial environment by dilation and wall thickening; however, the temporal regulation of the expression of extracellular matrix (ECM) components in the venous limb of the maturing AVF has not been well characterized. We used a murine model of AVF maturation that recapitulates human AVF maturation to determine the temporal pattern of expression of these ECM components.

Methods: Aortocaval fistulae were created in C57BL/6J mice and the venous limb was analyzed on postoperative days 1, 3, 7, 21, and 42.

Metabolic syndrome predicts restenosis after carotid endarterectomy.

Background: Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis for most patients. Restenosis after CEA can lead to additional interventions and adverse outcomes, but the factors that predict restenosis are poorly understood. This study examined which risk factors, such as metabolic syndrome (MetS), are associated with restenosis after CEA.

Chronic kidney disease predicts long-term mortality after major lower extremity amputation.

Background: Despite low peri-operative mortality after major lower extremity amputation, long-term mortality remains substantial. Metabolic syndrome is increasing in incidence and prevalence at an alarming rate in the USA.

Aim: This study was to determine whether metabolic syndrome predicts outcome after major lower extremity amputation.

Vein graft adaptation and fistula maturation in the arterial environment.

Veins are exposed to the arterial environment during two common surgical procedures, creation of vein grafts and arteriovenous fistulae (AVF). In both cases, veins adapt to the arterial environment that is characterized by different hemodynamic conditions and increased oxygen tension compared with the venous environment. Successful venous adaptation to the arterial environment is critical for long-term success of the vein graft or AVF and, in both cases, is generally characterized by venous dilation and wall thickening.

Metabolic syndrome is associated with type II endoleak after endovascular abdominal aortic aneurysm repair.

Objective: Type II endoleak is usually a benign finding after endovascular abdominal aortic aneurysm repair (EVAR). In some patients, however, type II endoleak leads to aneurysm sac expansion and the need for further intervention. We examined which factors, in particular the components of metabolic syndrome (MetS), would lead to an increase risk of endoleak after EVAR.

The mouse aortocaval fistula recapitulates human arteriovenous fistula maturation.

Several models of arteriovenous fistula (AVF) have excellent patency and help in understanding the mechanisms of venous adaptation to the arterial environment. However, these models fail to exhibit either maturation failure or fail to develop stenoses, both of which are critical modes of AVF failure in human patients. We used high-resolution Doppler ultrasound to serially follow mice with AVFs created by direct 25-gauge needle puncture.

Stem cell therapy for critical limb ischemia: what can we learn from cell therapy for chronic wounds?

Although much progress has been made regarding our knowledge of stem cells and their potential applications for therapeutic angiogenesis, there has been less success with the clinical application of this knowledge to patients with critical limb ischemia (CLI). Patients with CLI often have chronic wounds and newer cell-based therapies for chronic wounds show interesting parallels to stem cell therapy for CLI. Several human-derived wound care products and therapies, including human neonatal fibroblast-derived dermis (Dermagraft®), bilayered bioengineered skin substitute (Apligraf®), recombinant human platelet-derived growth factor and autologous platelet-rich plasma may provide insight into the mechanisms through which differentiated cells can be used as therapy for chronic wounds, and, analogously, by which stem cells might function therapeutically in CLI.

Cell-based interventions for therapeutic angiogenesis: review of potential cell sources.

Alternative therapies are currently being developed to treat patients with chronic limb ischemia who are unable to be revascularized in order to avoid amputation. Cell-based therapy using mononuclear cells is gaining attention as many clinical trials are currently underway. We review cell differentiation along with the different potential cell sources for use in therapeutic angiogenesis.

The influence of metabolic syndrome on hemodialysis access patency.

Objective: The natural history of patients with metabolic syndrome (MetS) undergoing hemodialysis access placement is unknown. MetS has previously been found as a risk factor for poor outcomes for vascular surgery patients undergoing other interventions. The aim of this is study is to describe the outcomes of MetS patients undergoing primary hemodialysis access placement.

Toward a mouse model of hind limb ischemia to test therapeutic angiogenesis.

Introduction: Several clinical trials are currently evaluating stem cell therapy for patients with critical limb ischemia that have no other surgical or endovascular options for revascularization. However, these trials are conducted with different protocols, including use of different stem cell populations and different injection protocols, providing little means to compare trials and guide therapy. Accordingly, we developed a murine model of severe ischemia to allow methodic testing of relevant clinical parameters.

Pericardial patch angioplasty heals via an Ephrin-B2 and CD34 positive cell mediated mechanism.

Objective: Pericardial patches are commonly used in vascular surgery to close arteriotomies. The mechanism of early healing after patch implantation is still not well defined. We used a rat aortic patch model to assess pericardial patch healing and examined Ephrin-B2, a marker of arterial identity, expression within the post-implantation patch.

Therapeutic strategies to combat neointimal hyperplasia in vascular grafts.

Neointimal hyperplasia (NIH) in bypass conduits such as veins and prosthetic grafts is an important clinical entity that limits the long-term success of vascular interventions. Although the development of NIH in the conduits shares many of the same features of NIH that develops in native arteries after injury, vascular grafts are exposed to unique circumstances that predispose them to NIH, including surgical trauma related to vein handling, hemodynamic changes creating areas of low flow, and differences in biocompatibility between the conduit and the host environment. Multiple different approaches, including novel surgical techniques and targeted gene therapies, have been developed to target and prevent the causes of NIH.

Influence of chronic renal insufficiency on outcomes following carotid revascularization.

Objectives: To examine the perioperative and long-term outcomes of patients undergoing carotid revascularization and to determine the influence moderate or severe renal insufficiency may have on these outcomes.

Design: Retrospective database review.

Setting: Academic tertiary hospital.

Renal artery interventions during infrarenal endovascular aortic repair: a greater potential of subsequent failure?

Purpose: To determine the anatomic and functional outcomes of renal artery interventions during endovascular aortic aneurysm repair (EVAR) and compare them with renal artery interventions without EVAR.

Materials And Methods: A renal artery revascularization database (1987-2007) was reviewed to identify patients who underwent renal intervention during EVAR and those who had an intervention in the absence of EVAR. Outcomes were analyzed with respect to patient comorbidities, renal anatomy and function, procedural events, and postoperative complications.

Cell migration in response to the amino-terminal fragment of urokinase requires epidermal growth factor receptor activation through an ADAM-mediated mechanism.

Background: Cell migration is an integral component of intimal hyperplasia development and proteases are pivotal in the process. Understanding the role of urokinase signaling within the cells of vasculature remains poorly defined. The study examines the role of amino-terminal fragment (ATF) of urokinase on a pivotal cross-talk receptor, epidermal growth factor receptor (EGFR).