scholarly journals Hyperthermia increases interleukin-6 in mouse skeletal muscle

2012 ◽  
Vol 303 (4) ◽  
pp. C455-C466 ◽  
Author(s):  
Steven S. Welc ◽  
Neil A. Phillips ◽  
Jose Oca-Cossio ◽  
Shannon M. Wallet ◽  
Daniel L. Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Core Temperature ◽  
Ex Vivo ◽  
C2c12 Myotubes ◽  
Tnf Α ◽  
Passive Hyperthermia ◽  
Circulating Levels ◽  
Cell Supernatant

Skeletal muscles produce and contribute to circulating levels of IL-6 during exercise. However, when core temperature is reduced, the response is attenuated. Therefore, we hypothesized that hyperthermia may be an important and independent stimulus for muscle IL-6. In cultured C2C12 myotubes, hyperthermia (42°C) increased IL-6 gene expression 14-fold after 1 h and 35-fold after 5 h of 37°C recovery; whereas exposure to 41°C resulted in a 2.6-fold elevation at 1 h. IL-6 protein was secreted and significantly elevated in the cell supernatant. Similar but reduced responses to heat were seen in C2C12 myoblasts. Isolated soleus muscles from mice, exposed ex vivo to 41°C for 1 h, yielded similar IL-6 gene responses (>3-fold) but without a significant effect on protein release. When whole animals were exposed to passive hyperthermia, such that core temperature increased to 42.4°C, IL-6 mRNA in soleus increased 5.4-fold compared with time matched controls. Interestingly, TNF-α gene expression was routinely suppressed at all levels of hyperthermia (40.5–42°C) in the isolated models, but TNF-α was elevated (4.2-fold) in the soleus taken from intact mice exposed, in vivo, to hyperthermia. Muscle HSP72 mRNA increased as a function of the level of hyperthermia, and IL-6 mRNA responses increased proportionally with HSP72. In cultured C2C12 myotubes, when heat shock factor was pharmacologically blocked with KNK437, both HSP72 and IL-6 mRNA elevations, induced by heat, were suppressed. These findings implicate skeletal muscle as a “heat stress sensor” at physiologically relevant hyperthermia, responding with a programmed cytokine expression pattern characterized by elevated IL-6.

scholarly journals A Fish-Derived Protein Hydrolysate Induces Postprandial Aminoacidaemia and Skeletal Muscle Anabolism in an In Vitro Cell Model Using Ex Vivo Human Serum

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 647
Author(s):  
Matthew J. Lees ◽  
David Nolan ◽  
Miryam Amigo-Benavent ◽  
Conor J. Raleigh ◽  
Neda Khatib ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Human Serum ◽  
Body Mass ◽  
Ex Vivo ◽  
Protein Hydrolysate ◽  
C2c12 Myotubes ◽  
The Impact

Fish-derived proteins, particularly fish protein hydrolysates (FPH), offer potential as high-quality sources of dietary protein, whilst enhancing economic and environmental sustainability. This study investigated the impact of a blue whiting-derived protein hydrolysate (BWPH) on aminoacidaemia in vivo and skeletal muscle anabolism in vitro compared with whey protein isolate (WPI) and an isonitrogenous, non-essential amino acid (NEAA) control (0.33 g·kg−1·body mass−1) in an ex vivo, in vitro experimental design. Blood was obtained from seven healthy older adults (two males, five females; age: 72 ± 5 years, body mass index: 24.9 ± 1.6 kg·m2) in three separate trials in a randomised, counterbalanced, double-blind design. C2C12 myotubes were treated with ex vivo human serum-conditioned media (20%) for 4 h. Anabolic signalling (phosphorylation of mTOR, p70S6K, and 4E-BP1) and puromycin incorporation were determined by immunoblotting. Although BWPH and WPI both induced postprandial essential aminoacidaemia in older adults above the NEAA control, peak and area under the curve (AUC) leucine and essential amino acids were more pronounced following WPI ingestion. Insulin was elevated above baseline in WPI and BWPH only, a finding reinforced by higher peak and AUC values compared with NEAA. Muscle protein synthesis, as measured by puromycin incorporation, was greater after incubation with WPI-fed serum compared with fasted serum (P = 0.042), and delta change was greater in WPI (P = 0.028) and BWPH (P = 0.030) compared with NEAA. Myotube hypertrophy was greater in WPI and BWPH compared with NEAA (both P = 0.045), but was similar between bioactive conditions (P = 0.853). Taken together, these preliminary findings demonstrate the anabolic potential of BWPH in vivo and ex vivo, thus providing justification for larger studies in older adults using gold-standard measures of acute and chronic MPS in vivo.

scholarly journals Exercise alters mRNA expression of telomere-repeat binding factor 1 in skeletal muscle via p38 MAPK

2012 ◽  
Vol 113 (11) ◽  
pp. 1737-1746 ◽  
Author(s):  
Andrew T. Ludlow ◽  
Laila C. J. Lima ◽  
Jenny Wang ◽  
Erik D. Hanson ◽  
Lisa M. Guth ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Mrna Expression ◽  
P38 Mapk ◽  
Treadmill Running ◽  
C2c12 Myotubes ◽  
Control Group ◽  
Telomere Repeat ◽  
Binding Factor

Telomeres protect chromosome ends and shorten with age in most tissues. Integral to the maintenance of telomeres is the protein complex shelterin. The gene expression regulation of shelterin proteins to physiological stressors is not understood in vivo. We have recently reported increased telomere-repeat binding factor 1 (TRF1) protein expression and longer telomere length in skeletal muscle of sedentary compared with chronically active mice. These provocative observations led us to examine the effects of acute physiological stress on shelterin expression in vivo in mice and to further define potential mechanisms associated with gene regulation of shelterin. Three groups of female C57Bl/6 mice were studied: one control group and two groups that underwent a 30-min treadmill running bout and were killed either immediately following or 1-h after the exercise. Following the exercise bout, mRNA expression of Trf1 was significantly reduced in the plantaris muscle, and this reduction was paralleled by significant increases in p38 MAPK phosphorylation. To determine if p38 mediated the decreases in Trf1 mRNA expression, C2C12 myotubes were treated with the calcium ionophore, A23187. In response to the A23187, Trf1 gene expression was significantly reduced, coupled with significant increases in p38 phosphorylation, similar to in vivo data. C2C12 myotubes pretreated with a p38 inhibitor (SB-202190) prevented the A23187-induced decrease in Trf1 mRNA expression, indicating a link between Trf1 gene expression and p38 MAPK activation. While it is too early to definitively report the effect of exercise on telomere biology in rodents or humans, these data provide important mechanistic insights into the paradoxical telomere shortening that occurs in skeletal muscle in response to chronic exercise in mice.

LPS-induced bronchial hyperreactivity: interference by mIL-10 differs according to site of delivery

2004 ◽  
Vol 286 (1) ◽  
pp. L98-L105 ◽  
Author(s):  
Virginie Deleuze ◽  
Jean Lefort ◽  
Michel F. Bureau ◽  
Daniel Scherman ◽  
B. Boris Vargaftig
Keyword(s):  
Protective Effect ◽  
Lung Inflammation ◽  
Inflammatory Cytokine ◽  
Ex Vivo ◽  
Blood Levels ◽  
Tnf Α ◽  
Circulating Levels ◽  
Anti Inflammatory Cytokine ◽  
Intranasal Instillation

When administered to mice systemically or via the airways, LPS induces bronchoconstriction (BC) and/or bronchopulmonary hyperreactivity (BHR), associated with inflammation. Accordingly, a relationship between inflammation and allergic and nonallergic BHR can be hypothesized. We therefore studied the interference of the anti-inflammatory cytokine murine IL-10 (mIL-10) with LPS-induced lung inflammation, BC, and BHR. mIL-10 was administered directly into the airways by intranasal instillation or generated in vivo after muscle electrotransfer of mIL-10-encoding plasmid. Electrotransfer led to high mIL-10 circulating levels for a longer time than after the injection of recombinant mIL-10 (rmIL-10). rmIL-10 administered intranasally reduced lung inflammation and BHR after LPS administration into airways. It also reduced the ex vivo production of TNF-α by LPS-stimulated lung tissue explants. Two days after electrotransfer, mIL-10 blood levels were elevated, but lung inflammation, BC, and BHR persisted unaffected. Blood mIL-10 reaches the airways poorly, which probably accounts for the ineffectiveness of mIL-10-encoding plasmid electrotransfer. When LPS was aerosolized 15 days after electrotransfer, lung inflammation persisted but BHR was significantly reduced, an effect that may be related to the longer exposure of the relevant cells to mIL-10. The dissociation between inflammation and BHR indicates that both are not directly correlated. In conclusion, this study shows that mIL-10 is efficient against BHR when present in the airway compartment. Despite this, the muscle electrotransfer with mIL-10-encoding plasmid showed a protective effect against BHR after a delay of 2 wk that should be further investigated.

scholarly journals Consequences of SUR2[A478V] Mutation in Skeletal Muscle of Murine Model of Cantu Syndrome

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1791
Author(s):  
Rosa Scala ◽  
Fatima Maqoud ◽  
Nicola Zizzo ◽  
Giuseppe Passantino ◽  
Antonietta Mele ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Katp Channel ◽  
Ex Vivo ◽  
Channel Modulation ◽  
Flexor Digitorum Brevis ◽  
Inflammatory Edema ◽  
Flexor Digitorum ◽  
Channel Currents

(1) Background: Cantu syndrome (CS) arises from gain-of-function (GOF) mutations in the ABCC9 and KCNJ8 genes, which encode ATP-sensitive K+ (KATP) channel subunits SUR2 and Kir6.1, respectively. Most CS patients have mutations in SUR2, the major component of skeletal muscle KATP, but the consequences of SUR2 GOF in skeletal muscle are unknown. (2) Methods: We performed in vivo and ex vivo characterization of skeletal muscle in heterozygous SUR2[A478V] (SUR2wt/AV) and homozygous SUR2[A478V] (SUR2AV/AV) CS mice. (3) Results: In SUR2wt/AV and SUR2AV/AV mice, forelimb strength and diaphragm amplitude movement were reduced; muscle echodensity was enhanced. KATP channel currents recorded in Flexor digitorum brevis fibers showed reduced MgATP-sensitivity in SUR2wt/AV, dramatically so in SUR2AV/AV mice; IC50 for MgATP inhibition of KATP currents were 1.9 ± 0.5 × 10−5 M in SUR2wt/AV and 8.6 ± 0.4 × 10−6 M in WT mice and was not measurable in SUR2AV/AV. A slight rightward shift of sensitivity to inhibition by glibenclamide was detected in SUR2AV/AV mice. Histopathological and qPCR analysis revealed atrophy of soleus and tibialis anterior muscles and up-regulation of atrogin-1 and MuRF1 mRNA in CS mice. (4) Conclusions: SUR2[A478V] “knock-in” mutation in mice impairs KATP channel modulation by MgATP, markedly so in SUR2AV/AV, with atrophy and non-inflammatory edema in different skeletal muscle phenotypes.

scholarly journals Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Natalia K. Kordulewska ◽  
Justyna Topa ◽  
Małgorzata Tańska ◽  
Anna Cieślińska ◽  
Ewa Fiedorowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Reaction ◽  
Wide Spectrum ◽  
Cell Monolayer ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle

2002 ◽  
Vol 283 (3) ◽  
pp. R698-R709 ◽  
Author(s):  
Robert A. Frost ◽  
Gerald J. Nystrom ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Cell Wall ◽  
Mrna Expression ◽  
Nuclear Factor Κb ◽  
Cytokine Expression ◽  
Mrna Accumulation ◽  
C2c12 Myoblasts ◽  
Tnf Α ◽  
Mrna Content

The purpose of the present study was to examine the regulation of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by lipopolysaccharide (LPS) in C2C12 myoblasts and mouse skeletal muscle. LPS produced dose- and time-dependent increases in TNF-α and IL-6 mRNA content in C2C12 myoblasts. The LPS-induced cytokine response could be mimicked by peptidoglycan from the cell wall of Staphylococcus aureus but not by zymosan A, a cell wall component from Saccharomyces cerevisiae. Ongoing protein synthesis was not necessary for the increase in the two cytokine mRNAs. The transcriptional inhibitor 5,6-dichloro-β-d-ribofuranosyl-benzimidazole blocked LPS-stimulated IL-6 mRNA expression without changing its mRNA half-life. The anti-inflammatory glucocorticoid dexamethasone selectively blocked LPS-stimulated IL-6 mRNA accumulation but not TNF-α. In contrast, the proteasomal inhibitor MG-132 blocked TNF-α mRNA expression but not IL-6. Exposure of myoblasts to LPS was associated with a rapid decrease in the inhibitor of nuclear factor-κB (I κB, α, and ε), and this response was also blocked by MG-132. Treatment of myocytes with IL-1 or TNF-α also increased IL-6 mRNA content, but the increase in IL-6 mRNA due to LPS could not be prevented by pretreatment with antagonists to either IL-1 or TNF. Under in vivo conditions, LPS increased the plasma concentration of TNF-α and IL-6 and stimulated the accumulation of their mRNAs in multiple tissues including skeletal muscle from wild-type mice. In contrast, the ability of LPS to stimulate the same cytokines was markedly decreased in mice that harbor a mutation in the Toll-like receptor 4. Our data suggest that LPS stimulates cytokine expression not only in classical immune tissues but also in skeletal muscle.

scholarly journals Healthy versus inflamed lung environments differentially effect MSCs

2021 ◽  
pp. 2004149
Author(s):  
Sara Rolandsson Enes ◽  
Thomas H. Hampton ◽  
Jayita Barua ◽  
David H. McKenna ◽  
Claudia C. dos Santos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy Volunteers ◽  
Cell Injury ◽  
Ex Vivo ◽  
Lavage Fluid ◽  
Cell Therapies ◽  
Inflammatory Microenvironment ◽  
Self Recognition ◽  
Clinical Investigations

BackgroundDespite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential in vivo mechanisms of MSC actions in ARDS remain limited. ARDS is driven by an acute severe innate immune dysregulation, often characterised by inflammation, coagulation, and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined.AimTo comparatively assess how the inflammatory environment present in ARDS lungs versus the lung environment present in healthy volunteers alters MSC behaviors.MethodsClinical grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties including viability, levels of expression of inflammatory cytokines, gene expression, cell surface HLA expression, and activation of coagulation and complement pathways.ResultsPro-inflammatory, pro-coagulant, and major histocompatibility complex (self recognition) related gene expression was markedly up-regulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. In contrast, these changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples.ConclusionThese data provide new insights into how hMSCs behave in healthy versus inflamed lung environments strongly suggesting that the inflamed environment in ARDS induces hMSC responses potentially benefical for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.

scholarly journals Combining Immunocytokine and Ex Vivo Activated NK Cells as a Platform for Enhancing Graft-Versus-Tumor Effects Against GD2+ Murine Neuroblastoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Paul D. Bates ◽  
Alexander L. Rakhmilevich ◽  
Monica M. Cho ◽  
Myriam N. Bouchlaka ◽  
Seema L. Rao ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Nk Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Tnf Α

Management for high-risk neuroblastoma (NBL) has included autologous hematopoietic stem cell transplant (HSCT) and anti-GD2 immunotherapy, but survival remains around 50%. The aim of this study was to determine if allogeneic HSCT could serve as a platform for inducing a graft-versus-tumor (GVT) effect against NBL with combination immunocytokine and NK cells in a murine model. Lethally irradiated C57BL/6 (B6) x A/J recipients were transplanted with B6 bone marrow on Day +0. On day +10, allogeneic HSCT recipients were challenged with NXS2, a GD2+ NBL. On days +14-16, mice were treated with the anti-GD2 immunocytokine hu14.18-IL2. In select groups, hu14.18-IL2 was combined with infusions of B6 NK cells activated with IL-15/IL-15Rα and CD137L ex vivo. Allogeneic HSCT alone was insufficient to control NXS2 tumor growth, but the addition of hu14.18-IL2 controlled tumor growth and improved survival. Adoptive transfer of ex vivo CD137L/IL-15/IL-15Rα activated NK cells with or without hu14.18-IL2 exacerbated lethality. CD137L/IL-15/IL-15Rα activated NK cells showed enhanced cytotoxicity and produced high levels of TNF-α in vitro, but induced cytokine release syndrome (CRS) in vivo. Infusing Perforin-/- CD137L/IL-15/IL-15Rα activated NK cells had no impact on GVT, whereas TNF-α-/- CD137L/IL-15/IL-15Rα activated NK cells improved GVT by decreasing peripheral effector cell subsets while preserving tumor-infiltrating lymphocytes. Depletion of Ly49H+ NK cells also improved GVT. Using allogeneic HSCT for NBL is a viable platform for immunocytokines and ex vivo activated NK cell infusions, but must be balanced with induction of CRS. Regulation of TNFα or activating NK subsets may be needed to improve GVT effects.

scholarly journals Effect of the proinflammatory cytokine TNF-α on intestinal riboflavin uptake: inhibition mediated via transcriptional mechanism(s)

2018 ◽  
Vol 315 (5) ◽  
pp. C653-C663 ◽  
Author(s):  
Kasin Yadunandam Anandam ◽  
Omar A. Alwan ◽  
Veedamali S. Subramanian ◽  
Padmanabhan Srinivasan ◽  
Rubina Kapadia ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Significant Inhibition ◽  
Mrna Levels ◽  
In Vivo Models ◽  
Uptake Inhibition ◽  
Tnf Α ◽  
Vitro Model ◽  
Factor Α

Riboflavin (RF), is essential for normal cellular metabolism/function. Intestinal RF absorption occurs via a specific carrier-mediated process that involves the apical transporter RFVT-3 ( SLC52A3) and the basolateral RFVT-1 (SLC52A1). Previously, we characterized different cellular/molecular aspects of the intestinal RF uptake process, but nothing is known about the effect of proinflammatory cytokines on the uptake event. We addressed this issue using in vitro, ex vivo, and in vivo models. First, we determined the level of mRNA expression of the human (h)RFVT-3 and hRFVT-1 in intestinal tissue of patients with inflammatory bowel disease (IBD) and observed a markedly lower level compared with controls. In the in vitro model, exposing Caco-2 cells to tumor necrosis factor-α (TNF-α) led to a significant inhibition in RF uptake, an effect that was abrogated upon knocking down TNF receptor 1 (TNFR1). The inhibition in RF uptake was associated with a significant reduction in the expression of hRFVT-3 and -1 protein and mRNA levels, as well as in the activity of the SLC52A3 and SLC52A1 promoters. The latter effects appear to involve Sp1 and NF-κB sites in these promoters. Similarly, exposure of mouse small intestinal enteroids and wild-type mice to TNF-α led to a significant inhibition in physiological and molecular parameters of intestinal RF uptake. Collectively, these findings demonstrate that exposure of intestinal epithelial cells to TNF-α leads to inhibition in RF uptake and that this effect is mediated, at least in part, via transcriptional mechanism(s). These findings may explain the significantly low RF levels observed in patients with IBD.

Abstract 249: Delayed Gene Transfer Increases Transgene Expression in Vein Grafts

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Liang Du ◽  
Jingwan Zhang ◽  
Alexander Clowes ◽  
David Dichek
Keyword(s):  
Gene Expression ◽  
Blood Flow ◽  
Gene Transfer ◽  
Transgene Expression ◽  
Ex Vivo ◽  
Arterial Blood Flow ◽  
Vein Grafts ◽  
Arterial Blood ◽  
En Face

Background Autogenous vein grafts are effective therapies for obstructive arterial disease. However, their long-term utility is limited by stenosis and occlusion. Genetic engineering of veins that prevents intimal hyperplasia and atherosclerosis could significantly improve the clinical utility of vein grafts. We recently reported that a helper-dependent adenoviral vector (HDAd) reduces atherosclerosis 4 wks after gene transfer in fat-fed rabbits and can express a therapeutic transgene (apo AI) in normal rabbit carotids for at least 48 wks. Use of HDAd for vein graft gene therapy will depend on achievement of similarly high and persistent transgene expression in grafted veins. Hypothesis We tested the hypothesis that Ad-mediated transgene expression in grafted veins (at an early time point) can be increased by varying the timing of gene transfer. Methods Rabbit external jugular veins were transduced by exposure to a beta galactosidase (b-gal)-expressing Ad: in situ either without (a) or with (b) immediate arterial grafting; c) ex vivo with grafting after overnight incubation with Ad; d) in vivo immediately after grafting and e) in vivo 4 wks after grafting (n = 6 - 19 veins/group). Transgene expression was measured in veins removed 3 d after Ad exposure by PCR quantitation of b-gal mRNA and by en-face planimetry of blue-stained area. Results B-gal transgene expression was higher in ungrafted veins than in veins grafted immediately after gene transfer (84 ± 17 vs 9.4 ± 2.0 arbitrary units (AU); P < 0.0001). Overnight incubation of veins with Ad increased gene expression ex vivo by 10-fold but neither this nor performing vector infusion immediately after grafting improved gene expression (11 ± 4.7 and 9.1 ± 1.8 AU; P > 0.9 for both vs immediately grafted veins). Delaying gene transfer until 4 wks after grafting significantly increased gene expression, to a level equivalent to transgene expression in ungrafted veins (61 ± 11 AU; P = 0.3 vs ungrafted veins). En face planimetry yielded similar results. Conclusions Exposure of a transduced vein to arterial blood flow is associated with significant loss of transgene expression. Transgene expression in grafted veins is significantly higher when gene transfer is performed 4 wks after exposure of the vein to arterial blood flow.

Sign in / Sign up

Export Citation Format

Share Document