Elevated serum bone morphogenetic protein 4 in patients with chronic kidney disease and coronary artery disease.

Chronic kidney disease (CKD) is associated with increased coronary artery disease (CAD) and coronary artery calcification. We hypothesized that the osteogenic factor, bone morphogenetic protein-4 (sBMP-4), is elevated in subjects with both CKD and CAD. Serum was collected from 79 subjects undergoing diagnostic angiography and stratified according to CAD and CKD status.

Use of a constitutively active hypoxia-inducible factor-1alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients: phase I dose-escalation experience.

Background: Critical limb ischemia, a manifestation of severe peripheral atherosclerosis and compromised lower-extremity blood flow, results in a high rate of limb loss. We hypothesized that adenoviral delivery of a constitutively active form of the transcription factor hypoxia-inducible factor-1alpha (ie, Ad2/HIF-1alpha/VP16 or HIF-1alpha) into the lower extremity of patients with critical limb ischemia would be safe and might result in a durable clinical response.

Methods And Results: This phase I dose-escalation program included 2 studies: a randomized, double-blind, placebo-controlled study and an open-label extension study.

Ultrasound velocity criteria for carotid in-stent restenosis.

Objective: To examine duplex ultrasound (US) criteria for carotid in-stent restenosis (ISR).

Background: Carotid artery stent (CAS) placement is an alternative to surgery for the treatment of carotid stenosis in high surgical risk patients. US is the primary method used to follow carotid stent patency.

Intra-arterial adenoviral mediated tumor transfection in a novel model of cancer gene therapy.

Background: The aim of the present study was to develop and characterize a novel in vivo cancer gene therapy model in which intra-arterial adenoviral gene delivery can be characterized. In this model, the rat cremaster muscle serves as the site for tumor growth and provides convenient and isolated access to the tumor parenchyma with discrete control of arterial and venous access for delivery of agents.

Results: Utilizing adenovirus encoding the green fluorescent protein we demonstrated broad tumor transfection.

Surveillance imaging for carotid in-stent restenosis.

Carotid artery stent placement is the procedure of choice in suitable candidates who require carotid revascularization and are at increased risk for surgical therapy. To ensure late patency of the stent, continued surveillance is required. We present three cases to illustrate the strengths and weaknesses of noninvasive imaging techniques for surveillance of carotid stents, ultimately validated with invasive contrast angiography.

Cellular, but not direct, adenoviral delivery of vascular endothelial growth factor results in improved left ventricular function and neovascularization in dilated ischemic cardiomyopathy.

Objectives: We sought to compare the effects on angiogenesis and left ventricular (LV) function of adenoviral vascular endothelial growth factor-165 (AdVEGF-165) gene delivery by direct injection of AdVEGF-165 to the transplantation of skeletal myoblasts (SKMB) transfected with AdVEGF-165 in a rat model of ischemic cardiomyopathy.

Background: Angiogenesis offers the potential for treating ischemic cardiomyopathy. However, the optimal method of delivering angiogenic factors for neovascularization remains undetermined.

Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication.

Background: "Therapeutic angiogenesis" seeks to improve perfusion by the growth of new blood vessels. The Regional Angiogenesis with Vascular Endothelial growth factor (RAVE) trial is the first major randomized study of adenoviral vascular endothelial growth factor (VEGF) gene transfer for the treatment of peripheral artery disease (PAD).

Methods And Results: This phase 2, double-blind, placebo-controlled study was designed to test the efficacy and safety of intramuscular delivery of AdVEGF121, a replication-deficient adenovirus encoding the 121-amino-acid isoform of vascular endothelial growth factor, to the lower extremities of subjects with unilateral PAD.

Protein kinase C mediates induced secretion of vascular endothelial growth factor by human glioma cells.

To understand how vascular endothelial growth factor (VEGF) production is activated in malignant glioma cells, we employed protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors to evaluate the extent to which these protein kinases were involved in signal transduction leading to VEGF production. PTK inhibitors blocked glioma proliferation and epidermal growth factor (EGF)-induced VEGF secretion, while H-7, a PKC inhibitor, inhibited both EGF-induced and baseline VEGF secretion. Phorbol 12-myristate 13-acetate (PMA), a non-specific activator of PKC, induced VEGF secretion by glioma cells, which was enhanced by calcium ionophore A23187, but completely blocked after prolonged treatment of cells with 1 microM PMA, by presumably depleting PKC.

Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy.

Background: Myocardial regeneration via stem-cell mobilisation at the time of myocardial infarction is known to occur, although the mechanism for stem-cell homing to infarcted tissue subsequently and whether this approach can be used for treatment of ischaemic cardiomyopathy are unknown. We investigated these issues in a Lewis rat model (ligation of the left anterior descending artery) of ischaemic cardiomyopathy.

Methods: We studied the effects of stem-cell mobilisation by use of granulocyte colony-stimulating factor (filgrastim) with or without transplantation of syngeneic cells.

Gene therapy by adenovirus-mediated vascular endothelial growth factor and angiopoietin-1 promotes perfusion of muscle flaps.

An experimental study was conducted to investigate the potential use of intravascular gene therapy with adenovirus-mediated (Ad) vascular endothelial growth factor (VEGF) or angiopoietin-1 (Ang-1) for the enhancement of muscle flap perfusion and to evaluate the effect of therapy on microcirculatory hemodynamics and microvascular permeability in vivo by using a cremaster muscle flap model in the rat. The cremaster tube flap was left intact after isolation of the pudo-epigastric pedicle. A total of 90 male Sprague-Dawley rats were divided into five groups of 18 each, according to the type of intraarterial treatment.

Enhancement of muscle flap hemodynamics by angiopoietin-1.

Angiopoietin-1 (Ang-1) constitutes a novel family of endothelial cell-specific angiogenic factors. Ang-1 functions mainly in remodeling, maturation, and stabilization of blood vessels. Its direct role in the process of angiogenesis remains unknown.

Adenovirus encoding vascular endothelial growth factor-D induces tissue-specific vascular patterns in vivo.

The capacity of an adenovirus encoding the mature form of vascular endothelial growth factor (VEGF)-D, VEGF-D Delta N Delta C, to induce angiogenesis, lymphangiogenesis, or both was analyzed in 2 distinct in vivo models. We first demonstrated in vitro that VEGF-D Delta N Delta C encoded by the adenovirus (Ad-VEGF-D Delta N Delta C) is capable of inducing endothelial cell proliferation and migration and that the latter response is primarily mediated by VEGF receptor-2 (VEGFR-2). Second, we characterized a new in vivo model for assessing experimental angiogenesis, the rat cremaster muscle, which permits live videomicroscopy and quantitation of functional blood vessels.

Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy.

A novel approach to treat ischemic tissues by using gene therapy has recently been introduced on the basis of the angiogenic potential of certain growth factors. The authors investigated the effect of adenovirus-mediated gene therapy with vascular endothelial growth factor (VEGF) delivered into the subdermal space to treat compromised skin flaps. For this purpose, the epigastric skin flap model in rats, based solely on the right inferior epigastric vessels, was used.

Tumor-infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a specific type of breast tumor that generally has a poor prognosis, in spite of recent advances in treatment. In the present study, semiquantitative reverse transcriptase polymerase chain reaction examination of resected specimens showed that angiogenic factors, not lymphangiogenic factors, are overexpressed in IBC tumors, compared with non-IBC tumors. Immunohistochemical analysis of the specimens revealed a significantly higher population of tumor-infiltrating (TI) endothelial cells (ECs) or endothelial precursor cells (EPCs) in tumor-associated stroma of IBC specimens than in non-IBC specimens.