Liposomal Nanocarriers Designed for Sub-Endothelial Matrix Targeting under Vascular Flow Conditions.

Vascular interventions result in the disruption of the tunica intima and the exposure of sub-endothelial matrix proteins. Nanoparticles designed to bind to these exposed matrices could provide targeted drug delivery systems aimed at inhibiting dysfunctional vascular remodeling and improving intervention outcomes. Here, we present the progress in the development of targeted liposomal nanocarriers designed for preferential collagen IV binding under simulated static vascular flow conditions.

Advances in the Formulation and Assembly of Non-Cationic Lipid Nanoparticles for the Medical Application of Gene Therapeutics.

Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake.

Dietary supplementation with Zyflamend poly-herbal extracts and fish oil inhibits intimal hyperplasia development following vascular intervention.

The polyherbal blend Zyflamend™ has been shown to have anti-inflammatory properties and attenuate inflammatory-modulated pathologies. Fish oils have also been shown to have cardioprotective properties. However, the beneficial effects of their combination have not been investigated.

The Efficacy of Systemic Doxycycline Administration as an Inhibitor of Intimal Hyperplasia after Balloon Angioplasty Arterial Injury.

Background: Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. Matrix metalloproteinases (MMPs) play a role in IH development due to their degradation of the extracellular matrix. Doxycycline (Doxy), a member of the tetracycline family of antibiotics, is a potent MMP inhibitor.

Cell mimetic liposomal nanocarriers for tailored delivery of vascular therapeutics.

Liposomal delivery systems (LDSs) have been at the forefront of medicinal nanotechnology for over three decades. Increasing LDS association to target cells and cargo delivery is crucial to bolstering overall nanodrug efficacy. Our laboratory aims to develop LDSs for molecular therapeutics aimed at vascular pathology.

Improving the efficacy of liposome-mediated vascular gene therapy via lipid surface modifications.

Background: We have previously defined mechanisms of intimal hyperplasia that could be targets for molecular therapeutics aimed at vascular pathology. However, biocompatible nanocarriers are needed for effective delivery. Cationic liposomes (CLPs) have been demonstrated as effective nanocarriers in vitro.

Testosterone replacement attenuates intimal hyperplasia development in an androgen deficient model of vascular injury.

Background: Androgen deficiency (AD) is associated with increased risk of vascular disease. Dysfunctional remodeling of the vessel wall and atypical proliferative potential of vascular smooth muscle cells (VSMCs) are fundamental processes in the development of intimal hyperplasia (IH). We have demonstrated an inverse relationship between dihydrotestosterone (DHT) levels, matrix metalloproteinase activity, and VSMC migration and proliferation in vitro.

Diabetic Foot Ulcers: The Importance of Patient Comorbidity Recognition and Total Contact Casting in Successful Wound Care.

Diabetic foot ulcers (DFUs) are a major burden on the health-care system. The purpose of this study is to investigate factors affecting the healing rate of DFU in a university wound care center. Records of DFU patients treated between July 2013 and February 2015 were reviewed.

Comparative analysis of polymers for short interfering RNA delivery in vascular smooth muscle cells.

Unlabelled: The use of short interfering RNA (siRNA) to degrade messenger RNA in the cell cytoplasm and transiently attenuate intracellular proteins shows promise in the inhibition of vascular pathogenesis. However, a critical obstacle for therapeutic application is a safe and effective delivery system. Biodegradable polymers are promising alternative molecular carriers for genetic material.

Low testosterone elevates interleukin family cytokines in a rodent model: a possible mechanism for the potentiation of vascular disease in androgen-deficient males.

Background: Androgen deficiency (AD) is associated with increased risk of atherosclerosis, cardiovascular, and peripheral arterial disease. Although the biochemical and molecular mechanisms underlying this risk remain unclear, higher testosterone (TST) levels correlate to significant immunoprotective molecular and cellular responses. Our group has previously demonstrated that female sex hormones influence vascular pathogenesis via inflammatory-modulated matrix metalloproteinase (MMP) regulation.

Androgens regulate MMPs and the cellular processes of intimal hyperplasia.

Background: Testosterone deficiency has been associated with an increased risk of vascular disease. Matrix metalloproteinases (MMPs) have been implicated in vascular remodeling. Our group has demonstrated an association between female hormones and MMP-modulated intimal hyperplasia.

Contemporary outcomes of vertebral artery injury.

Objective: Vertebral artery injury (VAI) associated with cervical trauma is being increasingly recognized with more aggressive screening. Disparate results from previous literature have led to uncertainty of the significance, natural history, and optimal therapy for VAI.

Methods: To understand the natural history and treatment outcomes from our experience, we performed a retrospective, single-center review from a level I trauma center for the previous 10 years of all VAI.

Effect of hormone replacement therapy in matrix metalloproteinase expression and intimal hyperplasia development after vascular injury.

Background: Postmenopausal women taking hormone replacement therapy (HRT) require secondary intervention after vascular reconstruction more frequently than women not taking HRT, often due to increased development of intimal hyperplasia (IH). Matrix metalloproteinases (MMPs) play a role in IH by degradation and remodeling of components of the vascular basement membrane. The MMP pathway is regulated by a balance between MMPs, membrane-type MMPs (MT-MMPs), and tissue inhibitor of MMPs (TIMPs).

Smooth muscle cell polymeric transfection is an efficient alternative to traditional methods of experimental gene therapy.

Background: Gene therapy shows promise in the treatment of vascular disease. However, traditional transfection methods commonly used in the laboratory are poorly translatable to in vivo conditions, primarily due to the immune response to viral vectors, the cellular toxicity of chemical transfection, and the technical impracticality of electroporation. Biodegradable polymers have shown promise as a safe, predictable, and nontoxic alternative, relying on endocytosis of synthetic polymeric carriers, which are bioconjugated to the targeted genetic material of choice.

Role of MT1-MMP in estrogen-mediated cellular processes of intimal hyperplasia.

Background: Hormone replacement therapy increases intimal hyperplasia (IH) following vascular intervention. Matrix metalloproteinases (MMPs) play a role in IH development. We have shown estrogen up-regulates MT1-MMP expression, a transmembrane protein that activates MMP-2, and increases vascular smooth muscle cell (VSMC) collagen invasion via increased MMP-2 activity.

Serum levels of matrix metalloproteinase-2 as a marker of intimal hyperplasia.

Background: A primary component in the development of intimal hyperplasia (IH) in response to vascular injury is basement membrane remodeling. Matrix metalloproteinases (MMPs) play a major role in this process by degradation of basement membrane proteins, mainly collagen type IV. Vascular injury initiates an inflammatory cascade with the release of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and C-reactive protein (CRP).

Endovascular aortic crossclamp: a novel way to reduce warm ischemia time in DCD donors.

Strategies like donation after cardiac death (DCD) have become more widely accepted to increase potential organ supply and decrease waiting list time. Warm ischemia time (WIT) is a key prognostic factor for organ function. Any process that can decrease WIT could decrease the number of discarded organs as well as improve graft and patient survival.

Development and validation of the Rapid Estimate of Adult Literacy in Vascular Surgery (REAL_VS).

The purposes of this study were to develop and validate the (1) Rapid Estimate of Adult Literacy in Vascular Surgery (REAL_VS) for researchers studying the impact of literacy skills as related to vascular surgery-related knowledge and outcomes and (2) short version of the REAL_VS (REAL_VSs) to allow clinicians to gauge their patients' familiarity with vascular surgery-related terms. A three-phase process was used to identify potential words for inclusion in the REAL_VS, including reviewing Internet-based patient education material content and listening to a random sample of 50 archived audiorecordings of vascular surgeon-patient encounters. The REAL_VS was composed of 75 terms (e.

Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure.

Objective: Postmenopausal women receiving hormone replacement therapy (HRT) have been reported to have more adverse outcomes after vascular reconstructions, including increased intimal hyperplasia development and bypass graft failure. HRT may be affecting the pathway contributing to intimal hyperplasia. An important component of this pathway involves matrix metalloproteinases (MMPs), implicated in vascular remodeling due to their ability to degrade components of the extracellular matrix.

Effect of hormones on matrix metalloproteinases gene regulation in human aortic smooth muscle cells.

Background: Postmenopausal women receiving hormone replacement therapy have more adverse outcomes after vascular reconstructions. Estrogen-binding receptors have been identified on vascular smooth muscle cells (VSMCs), indicating that vascular function may be under direct hormonal control. A key group of enzymes involved in vascular remodeling are matrix metalloproteinases (MMPs).

Can screening items identify surgery patients at risk of limited health literacy?

Background: Health literacy skills (HLS) have been shown to have a major impact on patient outcomes. To identify patients with limited or marginal HLS, the accuracy of three established screening items were examined.

Materials And Methods: We studied English-speaking adults (>or=21 years) attending a university-based vascular surgery clinic.

The importance of thrombophilia in the treatment of Paget-Schroetter syndrome.

Venous thoracic outlet syndrome (V-TOS) and associated subclavian vein thrombosis (SVT) result in significant patient morbidity and can be difficult to manage. Previous studies have suggested that both mechanical compressive factors and pathological alterations in patient coagulation may contribute to the development of SVT; however, no study has specifically evaluated the role of thrombophilia in the treatment of V-TOS and the need for long-term anticoagulation as an adjunct to surgical decompression. This retrospective study describes the clinical courses of 18 patients treated for V-TOS with and without acute SVT.

A case of external carotid artery pseudoaneurysm from hyoid bone fracture.

Carotid artery pseudoaneurysms are detected most commonly after acute traumatic injuries to the head and neck. Pseudoaneurysms of the carotid artery are rare after blunt trauma. The most common site of injury occurs in the internal carotid artery with greater than 70 per cent of those injuries resulting from motor vehicle collisions.

Bilateral renal rupture in a patient on hemodialysis.

This is a case presentation and discussion of a dialysis patient who presented to the surgical service with abdominal pain, hypotension, and tachycardia and in extremis who was found to have a contained retroperitoneal hematoma after rupture of his left kidney. Six months after an uneventful nephrectomy and postoperative recovery he again presented with hypotension and anemia and was found to have a contralateral retroperitoneal hematoma consistent with renal hemorrhage. After unsuccessful angioembolization, the patient underwent a right nephrectomy and recovered without sequelae.