scholarly journals In vivo cytokine profiling in peripheral arterial disease (PAD)

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
H. R . S . Girn ◽  
N.M. Orsi ◽  
S. Homer‐Vanniasinkam
Keyword(s):  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Peripheral Arterial ◽  
Cytokine Profiling

Abstract 5281: Bioluminescence Imaging of X-Ray Visible Microencapsulated Mesenchymal Stem Cells for Cell Based Therapy of Peripheral Arterial Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dorota A Kedziorek ◽  
Piotr Walczak ◽  
Yingli Fu ◽  
Nicole Azene ◽  
Aravind Arepally ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
X Ray ◽  
Encapsulated Cells ◽  
X Ray Imaging ◽  
Peripheral Arterial

Introduction: Therapeutic angiogenesis in Peripheral Arterial Disease (PAD) using stem cell therapy is potentially complicated by immunorejection. To overcome this problem, microen-capsulation using the alginate-poly-L-lysine (PLL)-alginate (APA) method was developed to provide a protective porous bubble to block antibodies but allow exchange of small molecules. Recently, we have developed a method to enable X-ray detection of these capsules. However, cell survival within the capsules could not be determined. Plus PLL can be mildly cytotoxic. In the present study, we combined reporter gene methods to verify cell survival with X-ray detection of the microcapsules in a rabbit PAD model and studied the PLL impact on cell viability. Methods: Rabbit mesenchymal stem cells (MSCs) were transfected with triple fusion (TF) reporter gene for bioluminescence (firefly luciferase), fluorescence (red fluorescent protein) and PET (truncated thymidine kinase). TF-MSCs were encapsulated in the perfluorooctyl bromide (PFOB) capsules to enable computed tomographic detection. Capsule crosslinking was performed with three PLL concentrations, i.e., 0.005%, 0.025% and 0.05%. Bioluminescent imaging (BLI) was used to monitor cells survival for one week in vitro and after intramuscular injection in vivo . Results: Serial in vitro BLI enabled the detection of viable encapsulated MSCs without detrimental signal degradation (~13% decrease of BLI signal intensity after PFOB encapsulation comparing to equal number of naked MSCs). PLL did not result in cell death; higher PLL concentrations were correlated with stronger BLI signal. BLI signal production was only slightly reduced by second layer of alginate (~80% for 0.05% PLL). In vivo BLI demonstrated the detection of naked, APA, and PFOB-encapsulated TF-MSCs. X-ray imaging enabled PFOB microcapsules detection relative to vasculature. Conclusion: BLI allows monitoring of encapsulated cells survival. PLL concentrations ≤ 0.05% appear safe for encapsulated cells with higher concentration being associated with enhanced crosslinking and capsule stability. MSCs expressing TF reporter in PFOB microcapsules enables dual monitoring of cell delivery/capsule tracking by X-ray imaging and cell viability with BLI.

scholarly journals Induced endothelial cells from peripheral arterial disease patients and neonatal fibroblasts have comparable angiogenic properties

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255075
Author(s):  
Jack D. Hywood ◽  
Sara Sadeghipour ◽  
Zoe E. Clayton ◽  
Jun Yuan ◽  
Colleen Stubbs ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Arterial Disease ◽  
Murine Model ◽  
Arterial Disease ◽  
Scid Mice ◽  
Laser Doppler ◽  
Cytokine Secretion ◽  
Endothelial Phenotype ◽  
Peripheral Arterial

Induced endothelial cells (iECs) generated from neonatal fibroblasts via transdifferentiation have been shown to have pro-angiogenic properties and are a potential therapy for peripheral arterial disease (PAD). It is unknown if iECs can be generated from fibroblasts collected from PAD patients and whether these cells are pro-angiogenic. In this study fibroblasts were collected from four PAD patients undergoing carotid endarterectomies. These cells, and neonatal fibroblasts, were transdifferentiated into iECs using modified mRNA. Endothelial phenotype and pro-angiogenic cytokine secretion were investigated. NOD-SCID mice underwent surgery to induce hindlimb ischaemia in a murine model of PAD. Mice received intramuscular injections with either control vehicle, or 1 × 106 neonatal-derived or 1 × 106 patient-derived iECs. Recovery in perfusion to the affected limb was measured using laser Doppler scanning. Perfusion recovery was enhanced in mice treated with neonatal-derived iECs and in two of the three patient-derived iEC lines investigated in vivo. Patient-derived iECs can be successfully generated from PAD patients and for specific patients display comparable pro-angiogenic properties to neonatal-derived iECs.

Skeletal muscle VEGF gradients in peripheral arterial disease: simulations of rest and exercise

2007 ◽  
Vol 293 (6) ◽  
pp. H3740-H3749 ◽  
Author(s):  
James W. Ji ◽  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Skeletal Muscle ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Basement Membranes ◽  
Vegf Receptor ◽  
Angiogenic Therapy ◽  
Vegf Signaling ◽  
Neuropilin 1 ◽  
Peripheral Arterial

VEGF is a key promoter of angiogenesis and a major target of proangiogenic therapy for peripheral arterial disease (PAD). Greater understanding of VEGF angiogenic signaling and guidance by gradients for new capillaries will aid in developing new proangiogenic therapies and improving existing treatments. However, in vivo measurements of VEGF concentration gradients at the cell scale are currently impossible. We have developed a computational model to quantify VEGF distribution in extensor digitorum longus skeletal muscle using measurements of VEGF, VEGF receptor (VEGFR), and neuropilin-1 (NRP1) expression in an experimental model of rat PAD. VEGF is secreted by myocytes, diffuses through and interacts with extracellular matrix and basement membranes, and binds VEGFRs and NRP1 on endothelial cell surfaces of blood vessels. We simulate the effects of increased NRP1 expression and of therapeutic exercise training on VEGF gradients, receptor signaling, and angiogenesis. Our study predicts that angiogenic therapy for PAD may be achieved not only through VEGF upregulation but also through modulation of VEGFRs and NRP1. We predict that expression of 104 NRP1/cell can increase VEGF binding to receptors by 1.7-fold (vs. no NRP1); in nonexercise-trained muscle with PAD, angiogenesis is hindered due to limited VEGF upregulation, signaling, and gradients; in exercise-trained muscle, VEGF signaling is enhanced by upregulation of VEGFRs and NRP1, and VEGF signaling is strongest within the first week of exercise therapy; and hypoxia-induced VEGF release is important to direct angiogenesis towards unperfused tissue.

scholarly journals ADAM12: a genetic modifier of preclinical peripheral arterial disease

2015 ◽  
Vol 309 (5) ◽  
pp. H790-H803 ◽  
Author(s):  
Ayotunde O. Dokun ◽  
Lingdan Chen ◽  
Mitsuharu Okutsu ◽  
Charles R. Farber ◽  
Surovi Hazarika ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Inbred Mouse ◽  
Genetic Modifier ◽  
Arterial Disease ◽  
Endothelial Cell Proliferation ◽  
Mouse Strains ◽  
Trait Locus ◽  
Peripheral Arterial

In prior studies from multiple groups, outcomes following experimental peripheral arterial disease (PAD) differed considerably across inbred mouse strains. Similarly, in humans with PAD, disease outcomes differ, even when there are similarities in risk factors, disease anatomy, arteriosclerotic burden, and hemodynamic measures. Previously, we identified a locus on mouse chromosome 7, limb salvage-associated quantitative trait locus 1 (LSq-1), which was sufficient to modify outcomes following experimental PAD. We compared expression of genes within LSq-1 in Balb/c mice, which normally show poor outcomes following experimental PAD, with that in C57Bl/6 mice, which normally show favorable outcomes, and found that a disintegrin and metalloproteinase gene 12 ( ADAM12) had the most differential expression. Augmentation of ADAM12 expression in vivo improved outcomes following experimental PAD in Balb/c mice, whereas knockdown of ADAM12 made outcomes worse in C57Bl/6 mice. In vitro, ADAM12 expression modulates endothelial cell proliferation, survival, and angiogenesis in ischemia, and this appeared to be dependent on tyrosine kinase with Ig-like and EGF-like domain 2 (Tie2) activation. ADAM12 is sufficient to modify PAD severity in mice, and this likely occurs through regulation of Tie2.

scholarly journals Delivery of hepatocyte growth factor mRNA from nanofibrillar scaffolds in a pig model of peripheral arterial disease

2020 ◽  
Vol 15 (6) ◽  
pp. 1761-1773
Author(s):  
Tatiana S Zaitseva ◽  
Guang Yang ◽  
Dimitris Dionyssiou ◽  
Maedeh Zamani ◽  
Steve Sawamura ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Therapeutic Potential ◽  
Arterial Disease ◽  
Translational Efficiency ◽  
Collagen Scaffolds ◽  
Vascular Regeneration ◽  
Peripheral Arterial ◽  
Hepatocyte Growth Factor Mrna

Background: Chemical modification of mRNA (mmRNA) substantially improves their stability and translational efficiency within cells. Nanofibrillar collagen scaffolds were previously shown to enable the spatially localized delivery and temporally controlled release of mmRNA encoding HGF both in vitro and in vivo. Materials & methods: Herein we developed an improved slow-releasing HGF mmRNA scaffold and tested its therapeutic efficacy in a porcine model of peripheral arterial disease. Results & conclusion: The HGF mmRNA was released from scaffolds in a temporally controlled fashion in vitro with preserved transfection activity. The mmRNA scaffolds improved vascular regeneration when sutured to the ligated porcine femoral artery. These studies validate the therapeutic potential of HGF mmRNA delivery from nanofibrillar scaffolds for treatment of peripheral arterial disease.

Ridogrel, a Combined Thromboxane Synthase Inhibitor and Receptor Blocker, Decreases Elevated Plasma β-Thromboglobulin Levels in Patients with Documented Peripheral Arterial Disease

1990 ◽  
Vol 64 (01) ◽  
pp. 087-090 ◽  
Author(s):  
B Hoet ◽  
J Arnout ◽  
C Van Geet ◽  
H Deckmyn ◽  
R Verhaeghe ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Single Molecule ◽  
Arterial Disease ◽  
Treated Group ◽  
Elevated Plasma ◽  
Double Blind ◽  
Thromboxane Synthase ◽  
Peripheral Arterial ◽  
Synthase Inhibitor

SummaryThe combination of thromboxane synthase inhibition with thromboxane receptor antagonism has been shown to result in a strong inhibition of platelet aggregation and a prolongation of the bleeding time (Gresele et al., J. Clin Invest 1987;80: 1435–45).Ridogrel is a single molecule that efficiently achieves both inhibitions in human volunteers. The present study was performed in patients with obstructive peripheral arterial disease and elevated plasma β-thromboglobulin levels. Patients were treated with either 2 × 300 mg ridogrel or 2 × 300 mg placebo per day for 2½ days, according to a double blind randomised parallel design. Plasma β-thromboglobulin decreased significantly throughout active treatment starting within 2 h after administration; serum and urinary immunoreactive TxB2 levels and urinary 11-dehydro- TxB2 excretion were significantly lower and serum PGE2 and 6-keto-PcF1α levels significantly higher with ridogrel; no changes were observed in the placebo-treated group.In conclusion this study demonstrates a reduction of platelet activation in vivo by ridogrel.

Enhancement of Peripheral Stents Reliability: Developing Interactive Procedure Planning by Means of Numerical Simulations and Clinical Software Development

2013 ◽  
Vol 7 (4) ◽  
Author(s):  
Claudio Silvestro ◽  
Massimo Morero ◽  
Roberto Ghidini ◽  
Carlo Guala ◽  
Gabriele Dubini ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Fracture Risk ◽  
Numerical Simulations ◽  
Real Time ◽  
Fatigue Fracture ◽  
Arterial Disease ◽  
Stent Fracture ◽  
Clinical Images ◽  
Peripheral Arterial

Around 20% of the population over 60-years-old have peripheral arterial disease. Symptoms can cause major lifestyle limitation through pain on walking (intermittent claudication). Progressive disease can also lead to critical limb ischemia, which is the major cause of amputation for adults. The implant of a stent is the endovascular therapy of election for the treatment of peripheral arterial disease. This, however, can increase the risk of fatigue fracture of the implanted device, under in vivo loading conditions. RT3S (real time simulations for safer vascular stenting) is a scientific project involving both universities and private companies, for a funded budget of more than $4.5 million (www.rt3s.eu). The project aims at providing physicians with interactive clinical software for an enhanced pre-operative planning of femoral artery stenting including a prediction of in vivo stent fracture risk, computed by means of numerical simulations. Software-developing companies developed an interactive application allowing physicians to upload the patient's clinical images and plan the stenting procedure, estimating the device fatigue fracture risk, for a specific case of stent and anatomical geometry/boundary conditions. Thanks to the application of innovative response surface techniques, results obtained with the numerical model (requiring 8-day running time) can be exploited quasi real time by the software user. Outcomes of the project will be also exploited for designing activities of next-generation stent devices.

scholarly journals In Vivo Confirmation of the Role of Statins in Reducing Nitric Oxide and C-Reactive Protein Levels in Peripheral Arterial Disease

2009 ◽  
Vol 37 (4) ◽  
pp. 443-447 ◽  
Author(s):  
E. Martínez Aguilar ◽  
J. De Haro Miralles ◽  
A. Flórez González ◽  
C. Varela Casariego ◽  
S. Bleda Moreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Peripheral Arterial

Platelet Activation During Treadmill Exercise In Patients With Chronic Peripheral Arterial Disease

1981 ◽  
Author(s):  
G Baele ◽  
H Bogaerts ◽  
D L Clement ◽  
R Pannier ◽  
F Barbier
Keyword(s):  
Peripheral Arterial Disease ◽  
Platelet Activation ◽  
Plasma Levels ◽  
Treadmill Exercise ◽  
Arterial Disease ◽  
Mean Value ◽  
Platelet Factor ◽  
Normal Individuals ◽  
Peripheral Arterial

β-Thromboglobulin (β-TG) and platelet factor 4 (PF-4) are specific platelet proteins released during in vivo platelet activation. An increase in PF-4 after exercise- induced myocardial ischemia was reported by Green, L.H. et al.. This observation prompted us to measure β-TG and PF-4 in patients with chronic occlusive arterial disease of the lower limbs and to look for increments during treadmill exercise. β-TG was measured using the Amersham test kit and PF-4 using the radioimmunoassay kit of Abbott Diagnostics Division. Plasma levels in 28 normal individuals ranged for β-TG from 7 to 39 ng/ml with a mean value of 21.0 ng/ml, for PF-4 from 1 to 19 ng/ml with a mean value of 6.0 ng/ml. β-TG and PF-4 were measured in 59 patients with chronic peripheral arterial disease before and 5 min. after treadmill exercising till occurrence of claudication. Plasma levels of β-TG before treadmill exercising ranged from 24 to 260 ng/ml with a mean of 77.9 ng/ml, PF-4 levels ranged from 2 to 240 ng/ml with a mean of 30.4 ng/ml. These levels were significantly higher than those measured in normal individuals.After treadmill exercise β-TG levels showed a statistically significant increase to a mean value of 87.3 ng/ml but PF-4 did not rise significantly (mean value : 32.4 ng/ml). The supplementary increase of already elevated β-TG levels may be explained by enhanced in vivo platelet activation during treadmill exercising till occurrence of claudication. As the clearance of PF-4 from human plasma has been shown to be much faster than the clearance of β-TG increases in PF-4 levels may be more difficult to detect during dynamic explorations of the vascular system.

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