The Experts below are selected from a list of 2004 Experts worldwide ranked by ideXlab platform
Jesús Prieto - One of the best experts on this subject based on the ideXlab platform.
-
Cardiotrophin 1 is an anti inflammatory cytokine and promotes il 4 induced m2 macrophage polarization
The FASEB Journal, 2019Co-Authors: David Carneros, Eduardo Larequi, Eva M Santamaria, Jose Miguel Velezortiz, Mercedes Reboredo, Uxua Mancheno, Maria J Perugorria, Placido Navas, Manuel Romerogomez, Jesús PrietoAbstract:Macrophages play a central role in tissue remodeling, repair, and resolution of inflammation. Macrophage polarization to M1 or M2 activation status may determine the progression or resolution of the inflammatory response. We have previously reported that Cardiotrophin-1 (CT-1) displays both cytoprotective and metabolic activities. The role of CT-1 in inflammation remains poorly understood. Here, we employed recombinant CT-1 (rCT-1) and used CT-1-null mice and myeloid-specific CT-1 transgenic mice to investigate whether CT-1 might play a role in the modulation of the inflammatory response. We observed that CT-1 deficiency was associated with enhanced release of inflammatory mediators and with stronger activation of NF-κB in response to LPS, whereas the inflammatory response was attenuated in CT-1 transgenic mice or by administering rCT-1 to wild-type animals prior to LPS challenge. We found that CT-1 promoted IL-6 expression only by nonhematopoietic cells, whereas LPS up-regulated IL-6 expression in both hematopoietic and nonhematopoietic cells. Notably, rCT-1 inhibited LPS-mediated soluble IL-6R induction. Using IL-6-/- mice, we showed that rCT-1 inhibited LPS-induced TNF-α and IFN-γ response in an IL-6-independent manner. Importantly, we demonstrated that CT-1 primes macrophages for IL-4-dependent M2 polarization by inducing IL-4 receptor expression. Mechanistic analyses showed that the signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 axis mediates this effect. Our findings support the notion that CT-1 is a critical regulator of inflammation and suggest that rCT-1 could be a molecule with potential therapeutic application in inflammatory conditions.-Carneros, D., Santamaria, E. M., Larequi, E., Velez-Ortiz, J. M., Reboredo, M., Mancheno, U., Perugorria, M. J., Navas, P., Romero-Gomez, M., Prieto, J., Hervas-Stubbs, S., Bustos, M. Cardiotrophin-1 is an anti-inflammatory cytokine and promotes IL-4-induced M2 macrophage polarization.
-
Role of Cardiotrophin-1 in obesity and insulin resistance
2016Co-Authors: María J. Moreno-aliaga, David Castaño, Jesús Prieto, Asunción M. Romero-lozano, Matilde BustosAbstract:Abbreviations: CT-1, Cardiotrophin-1; IL, interleukin; LIF, leukemia inhibitory factor; CNTF, ciliary neurotrophic factor; OSM, oncostatin M; CLC, Cardiotrophin like cytokine; NP, neuropoietin; STAT, signal transducer and activator of transcription; EE, energy expenditure; rCT-1, recombinant CT-1; WAT, white adipose tissue; UCP1, uncoupling protein 1; Dio2, deiodinase iodothyronine type II; TNF-a, tumor necrosis factor-a; PAI-1, plasminogen activator inhibitor-1; ROS, reactive oxygen species; SOCS, suppressor of cytokine signaling; IRS, insulin receptor substrate; GLP-1, glucagon-like-peptide-1; ITT, insulin tolerance test; FFA, free fatty acids; cAMP, cyclic adenosine monophosphate; STZ, streptozotoci
-
Cardiotrophin 1 reduces ischemia reperfusion injury during liver transplant
Journal of Surgical Research, 2013Co-Authors: Patricia Aguilarmelero, A. Luque, María Del Mar Granados Machuca, María P. Pérez De Obanos, Rocío Navarrete, Javier Briceño, Maria Iñiguez, Juan Carlos Ruiz, Ines C Rodriguezgarcia, Jesús PrietoAbstract:Abstract Background Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. Materials and methods We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. Results Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. Conclusions The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
-
Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant.
The Journal of surgical research, 2012Co-Authors: Patricia Aguilar-melero, A. Luque, María Del Mar Granados Machuca, María P. Pérez De Obanos, Rocío Navarrete, Inés C. Rodríguez-garcía, Javier Briceño, Maria Iñiguez, Juan Carlos Ruiz, Jesús PrietoAbstract:Abstract Background Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. Materials and methods We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. Results Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. Conclusions The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
-
Role of Cardiotrophin-1 in obesity and insulin resistance.
Adipocyte, 2012Co-Authors: María J. Moreno-aliaga, M. Asunción Romero-lozano, David Castaño, Jesús Prieto, Matilde BustosAbstract:Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. In a recent study we examined the metabolic features of ct-1 null mice and the effects on body composition, glucose and lipid metabolism of acute and chronic administration of recombinant CT-1. Our data revealed that CT-1 is a key regulator of energy metabolism with potential applications in the treatment of obesity and the metabolic syndrome. This commentary discusses the significance of these findings in the context of other key studies in the field of obesity and insulin resistance.
Javier Diez - One of the best experts on this subject based on the ideXlab platform.
-
association of Cardiotrophin 1 with myocardial fibrosis in hypertensive patients with heart failure
Hypertension, 2014Co-Authors: Begona Lopez, Arantxa Gonzalez, Ramon Querejeta, Mariano Larman, Gregorio Rabago, Javier DiezAbstract:Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether Cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial Cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (P<0.001). Cardiotrophin-1 overexpression in patients was localized in cardiomyocytes. Cardiotrophin-1 protein was correlated with collagen type I and III mRNAs (r=0.653, P<0.001; r=0.541, P<0.01) and proteins (r=0.588, P<0.001; r=0.556, P<0.005) in all subjects and with left ventricular end-diastolic wall stress (r=0.450; P<0.05) in patients. Plasma Cardiotrophin-1 and N-terminal pro-brain natriuretic peptide and serum biomarkers of myocardial fibrosis (carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III) were increased (P<0.001) in patients compared with controls. Plasma Cardiotrophin-1 was correlated with N-terminal pro-brain natriuretic peptide (r=0.386; P<0.005), carboxy-terminal propeptide of procollagen type I (r=0.550; P<0.001), and amino-terminal propeptide of procollagen type III (r=0.267; P<0.05) in all subjects. In vitro, Cardiotrophin-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts (P<0.05) and the expression of procollagen type I (P<0.05) and III (P<0.01) mRNAs. These findings show that an excess of Cardiotrophin-1 is associated with increased collagen in the myocardium of hypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of Cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin.
-
Association of Cardiotrophin-1 With Myocardial Fibrosis in Hypertensive Patients With Heart Failure
Hypertension (Dallas Tex. : 1979), 2013Co-Authors: Begona Lopez, Arantxa Gonzalez, Ramon Querejeta, Mariano Larman, Gregorio Rabago, Javier DiezAbstract:Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether Cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial Cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (P
-
Cardiotrophin-1 in hypertensive heart disease.
Endocrine, 2012Co-Authors: Arantxa Gonzalez, Begona Lopez, Susana Ravassa, Javier Beaumont, Amaia Zudaire, Idoia Gallego, Cristina Brugnolaro, Javier DiezAbstract:Hypertensive heart disease, here defined by the presence of pathologic left ventricular hypertrophy in the absence of a cause other than arterial hypertension, is characterized by complex changes in myocardial structure including enhanced cardiomyocyte growth and non-cardiomyocyte alterations that induce the remodeling of the myocardium, and ultimately, deteriorate left ventricular function and facilitate the development of heart failure. It is now accepted that a number of pathological processes mediated by mechanical, neurohormonal, and cytokine routes acting on the cardiomyocyte and the non-cardiomyocyte compartments are responsible for myocardial remodeling in the context of arterial hypertension. For instance, Cardiotrophin-1 is a cytokine member of the interleukin-6 superfamily, produced by cardiomyocytes and non-cardiomyocytes in situations of biomechanical stress that once secreted interacts with its receptor, the heterodimer formed by gp130 and gp90 (also known as leukemia inhibitory factor receptor beta), activating different signaling pathways leading to cardiomyocyte hypertrophy, as well as myocardial fibrosis. Beyond its potential mechanistic contribution to the development of hypertensive heart disease, Cardiotrophin-1 offers the opportunity for a new translational approach to this condition. In fact, recent evidence suggests that Cardiotrophin-1 may serve as both a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients, and a potential target for therapies aimed to prevent and treat hypertensive heart disease beyond blood pressure control.
-
Association of plasma Cardiotrophin-1 with stage C heart failure in hypertensive patients: potential diagnostic implications.
Journal of hypertension, 2009Co-Authors: Begona Lopez, Arantxa Gonzalez, Ramon Querejeta, Joaquín Barba, Javier DiezAbstract:Cardiotrophin-1 is a cytokine that induces hypertrophy and dysfunction in cardiomyocytes and has been shown to be increased in hypertensive patients. The objective of this study was to evaluate the association of Cardiotrophin-1 with heart failure (HF) in hypertensive patients and its usefulness as a biomarker of stage C heart failure. Hypertensive patients without cardiac abnormalities (stage A, n = 64), with left ventricular hypertrophy (LVH) (stage B, n = 58), and with left ventricular hypertrophy and clinical manifestations of chronic heart failure (stage C, n = 39) were studied. Plasma Cardiotrophin-1 was measured by an enzyme-linked inmunosorbent assay. Plasma Cardiotrophin-1 progressively increased (P < 0.001), along with progression of heart failure stages, in hypertensive patients. Plasma Cardiotrophin-1 was directly (r = 0.416, P < 0.001) and inversely (r = 0.263, P < 0.01) correlated with left ventricular (LV) mass index and ejection fraction, respectively, in all hypertensive patients. These associations were independent of a number of potential confounding factors. Receiver operating characteristic curves showed that a cut-off of 48.72 fmol/ml for Cardiotrophin-1 provided higher sensitivity for diagnosing stage C heart failure than a cut-off of 375.54 pg/ml for amino-terminal probrain natriuretic peptide (NT-proBNP) (80% vs. 72%). Sixty-four percent of stage C hypertensive patients with NT-proBNP values below 375.54 pg/ml value exhibited Cardiotrophin-1 values above 49.16 fmol/ml. These findings indicate that plasma Cardiotrophin-1 is associated with progression of heart failure in hypertensive patients. Cardiotrophin-1 measurement may provide additional information to that afforded by NT-proBNP to diagnose stage C heart failure in these patients.
-
Aldosterone induces Cardiotrophin-1 expression in HL-1 adult cardiomyocytes.
Endocrinology, 2008Co-Authors: Natalia López-andrés, Javier Diez, Idoia Gallego, Carmen Iñigo, M.a. FortuñoAbstract:Aldosterone (ALDO) may induce cardiac hypertrophy by nonhemodynamic mechanisms that are not completely defined. Cardiotrophin-1 (CT-1) is a cytokine that exerts hypertrophic actions on isolated cardiomyocytes and promotes cardiac hypertrophy in vivo. We investigated whether ALDO induces CT-1 expression in HL-1 cardiomyocytes aiming at the possibility that the cytokine is involved in ALDO-induced cardiomyocyte hypertrophy. mRNA and protein expression were quantified by RT-PCR and Western blot. Cardiomyocyte area, as an index of hypertrophy, was assayed by image analysis in phalloidin-stained HL-1 cells. ALDO addition to adult HL-1 cardiomyocytes increased (P < 0.01) CT-1 mRNA and protein expression in a concentration-dependent manner. This effect was abrogated by actinomycin D, the mineralocorticoid and glucocorticoid receptor antagonists spironolactone and RU486, respectively, and the p38 MAPK blocker SB203580. CT-1 signaling pathway blockade with specific antibodies against the cytokine and its two recep...
Diane Pennica - One of the best experts on this subject based on the ideXlab platform.
-
Cardiotrophin-1 induces the same neuropeptides in sympathetic neurons as do neuropoietic cytokines.
Journal of neurochemistry, 2002Co-Authors: Gang Cheng, Diane Pennica, Paul H. PattersonAbstract:Cardiotrophin-1 (CT-1) was cloned from mouse embryoid body for its ability to induce growth of heart cells. Predictions of its secondary structure indicate that CT-1 belongs to a family of cytokines with a four-helical bundle structure, and sequence comparisons reveal a weak homology to leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF). Using a reverse transcriptase-polymerase chain reaction assay with rat sympathetic neuron cultures, we find that CT-1 induces and suppresses the expression of the same set of neuropeptide and neurotransmitter synthetic enzyme mRNAs as do LIF and CNTF. In addition, the effects of CT-1 and LIF are not additive, and CT-1 does not require a GPI-linked component to mediate its actions. Our functional data confirm that CT-1 is a member of the neuropoietic cytokine family and suggest that the CT-1 receptor complex contains the gp130 signal transducing component.
-
Effects of Cardiotrophin-1 (CT-1) in a mouse motor neuron disease
Muscle & nerve, 2001Co-Authors: Hiroshi Mitsumoto, Rhona M. O'leary, Bogdan Klinkosz, Erik P. Pioro, Kazufumi Tsuzaka, Takeo Ishiyama, Diane PennicaAbstract:Cardiotrophin-1 (CT-1) has potent survival-promoting effects on motor neurons in vitro and in vivo and may be effective in treating motor neuron diseases (MND). We investigated the effects of CT-1 treatment in wobbler mouse MND. Wobbler mice were randomly assigned to receive subcutaneously injected CT-1 (1 mg/kg, n = 18, in two experiments) or vehicle (n = 18, in two experiments) daily, 6 times/week for 4 weeks after clinical diagnosis at age 3 to 4 weeks. Cardiotrophin-1 treatment prevented deterioration in paw position and walking pattern abnormalities. Grip strength declined steadily in the vehicle group, whereas in the CT-1 group it declined at week 1 but increased thereafter to exceed baseline strength by 5% (P = 0.0002) at week 4. Running speed was faster with CT-1 (P = 0.007). Biceps muscle twitch tension, muscle weight, mean muscle fiber diameter, and intramuscular axonal sprouting were significantly greater with CT-1 treatment than with vehicle treatment. Histometry revealed a trend that indicated CT-1 modestly increased the number of immunoreactive motor neurons, as determined by both choline acetyltransferase and c-Ret antibodies, and reduced the number of phosphorylated neurofilament immunoreactive perikarya (P = 0.05). The number of large myelinated motor axons significantly increased with treatment (206 versus 113, P = 0.01). We conclude that CT-1 exerts myotrophic effects as well as neurotrophic effects in a mouse model of spontaneous MND, a finding that has potential therapeutic implications for human MND.
-
Cardiotrophin-1 reduces stress-induced heat shock protein production in cardiac myocytes.
Cytokine, 2000Co-Authors: Julia E. Railson, Diane Pennica, Kevin M. Lawrence, Anastasou Stephanou, Bhawanjit K. Brar, David S. LatchmanAbstract:Cardiotrophin-1 (CT-1) can induce expression of the protective heat shock proteins (hsps) in cardiac cells. We show here that, unlike the stress induced accumulation of hsps, the effect of CT-1 is not accompanied by increased hsp mRNA levels and is insensitive to the RNA synthesis inhibitor actinomycin D, suggesting that it occurs at the post-transcriptional level. Pre-treatment with CT-1 reduces the ability of heat shock to induce hsp expression and this effect occurs at the transcriptional level. Hence, CT-1 and stress induce the hsps via different pathways which can antagonise one another. The mechanisms of these effects and their potential impact on the use of CT-1 as a cardioprotective agent are discussed.
-
Cardiotrophin-1 attenuates endotoxin-induced acute lung injury.
The Journal of surgical research, 1999Co-Authors: Edward J. Pulido, Diane Pennica, Brian D. Shames, Rhona M. O'leary, Denis D. Bensard, Brian S. Cain, Robert C. McintyreAbstract:Cardiotrophin-1 (CT-1) is a recently discovered member of the gp130 cytokine family, which includes IL-6, IL-11, leukemia inhibitory factor, ciliary neurotrophic factor, and oncostatin M. Recent evidence suggests that, like other members of this family, CT-1 may possess anti-inflammatory properties. We hypothesized that in vivo CT-1 administration would attenuate endotoxin (ETX)-induced acute lung injury. We studied the effects of CT-1 (100 μg/kg ip, 10 min prior to ETX) in a rat model of ETX-induced acute lung injury (Salmonella typhimurium lipopolysaccharide, 20 mg/kg ip). Six hours after ETX, lungs were harvested for determination of neutrophil accumulation (myeloperoxidase, MPO, assay) and lung edema (wet-to-dry weight ratio). Mechanisms of pulmonary vasorelaxation were examined in isolated pulmonary artery rings at 6 h by interrogating endothelium-dependent (response to acetylcholine) and endothelium-independent (response to sodium nitroprusside) relaxation following α-adrenergic (phenylephrine)-stimulated preconstriction. CT-1 abrogated the endotoxin-induced lung neutrophil accumulation: 2.3 ± 0.2 units MPO/g wet lung (gwl) vs 6.3 ± 0.3 units MPO/gwl in the ETX group (P 0.05 vs control). Similarly, CT-1 prevented ETX-induced lung edema: wet-to-dry-weight ratio, 4.473 ± 0.039 vs 4.747 ± 0.039 in the ETX group (P 0.05 vs control). Endotoxin caused significant impairment of both endothelium-dependent and -independent pulmonary vasorelaxation, and CT-1 attenuated this injury. Thus, Cardiotrophin-1 possesses significant anti-inflammatory properties in a model of endotoxin-induced acute lung injury.
-
Overexpression of Cardiotrophin-1 and gp130 during experimental acute Chagasic cardiomyopathy
Immunology Letters, 1998Co-Authors: Bysani Chandrasekar, Diane Pennica, Peter C. Melby, Gregory L. FreemanAbstract:Abstract Cardiotrophin-1 (CT-1), a cytokine with structural similarities to interleukin-6, has been shown to signal through gp130-dependent pathways. In vitro, CT-1 promotes the survival and induces hypertrophy of neonatal cardiomyocytes. Since acute Chagas' disease involves an inflammatory response followed by chamber dilation, with subsequent compensatory hypertrophy, we hypothesized CT-1 and gp130 may participate in this disease process. Thus, we investigated expression and localization of these moieties during acute Chagasic cardiomyopathy. Lewis rats ( n =6/group) were either inoculated with cell culture-derived T. cruzi trypomastigotes or saline, and sacrificed 15 days later. Hearts were collected for histology, immunohistochemistry (IHC), mRNA, and protein analyses. Histology showed dense myocardial infection with amastigotes and diffuse mononuclear cell infiltrate. Northern blot analysis showed low level expression of CT-1 mRNA in controls, which was markedly elevated in infected animals (2.5-fold; P P
A. Luque - One of the best experts on this subject based on the ideXlab platform.
-
Cardiotrophin 1 reduces ischemia reperfusion injury during liver transplant
Journal of Surgical Research, 2013Co-Authors: Patricia Aguilarmelero, A. Luque, María Del Mar Granados Machuca, María P. Pérez De Obanos, Rocío Navarrete, Javier Briceño, Maria Iñiguez, Juan Carlos Ruiz, Ines C Rodriguezgarcia, Jesús PrietoAbstract:Abstract Background Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. Materials and methods We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. Results Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. Conclusions The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
-
Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant.
The Journal of surgical research, 2012Co-Authors: Patricia Aguilar-melero, A. Luque, María Del Mar Granados Machuca, María P. Pérez De Obanos, Rocío Navarrete, Inés C. Rodríguez-garcía, Javier Briceño, Maria Iñiguez, Juan Carlos Ruiz, Jesús PrietoAbstract:Abstract Background Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. Materials and methods We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. Results Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. Conclusions The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
Maria Iñiguez - One of the best experts on this subject based on the ideXlab platform.
-
Cardiotrophin 1 reduces ischemia reperfusion injury during liver transplant
Journal of Surgical Research, 2013Co-Authors: Patricia Aguilarmelero, A. Luque, María Del Mar Granados Machuca, María P. Pérez De Obanos, Rocío Navarrete, Javier Briceño, Maria Iñiguez, Juan Carlos Ruiz, Ines C Rodriguezgarcia, Jesús PrietoAbstract:Abstract Background Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. Materials and methods We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. Results Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. Conclusions The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
-
Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant.
The Journal of surgical research, 2012Co-Authors: Patricia Aguilar-melero, A. Luque, María Del Mar Granados Machuca, María P. Pérez De Obanos, Rocío Navarrete, Inés C. Rodríguez-garcía, Javier Briceño, Maria Iñiguez, Juan Carlos Ruiz, Jesús PrietoAbstract:Abstract Background Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. Materials and methods We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. Results Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. Conclusions The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.