Oscar Lopez-Franco
@uv.mx
Traslacional Medicine Laboratory. Instituto de Ciencias de la Salud
Universidad Veracruzana
Dr. Óscar López-Franco is a Senior Research in University of Veracruz-México. Graduate in Biochemistry by Complutense University and Doctorate with Honours by Autonoma University (Madrid-Spain, 1998 and 2004, respectively). More than 20 years of research experience. During this time (from 1999 to 2013) he has worked in three laboratories: Renal and Vascular Research Group (Jimenez Diaz Foundation, Madrid, Spain); Cardiovascular Research Group and Biomedical Research Group, both in University of Glasgow, UK. Since 2014, he has led the group “Translational Medicine” in the Health Science Institute of the University of Veracruz. His research activities focus on the molecular mechanisms of immune renal, diabetes and atherosclerosis diseases, with special interest in Fc receptors, SOCS proteins, gene therapy and microRNAs. Working as part of a multidisciplinary groups composed of both scientist and clinicians has been invaluable in developing research projects.
EDUCATION
Graduate in Biochemistry by Complutense University (Madrid-Spain, 1998)
Doctorate with Honours by Autonoma University (Madrid-Spain, 2004)
RESEARCH, TEACHING, or OTHER INTERESTS
Molecular Medicine, Drug Discovery, Biochemistry, Genetics and Molecular Biology
Scopus Publications
Scopus Publications
Ignacio Prieto, María Kavanagh, Luna Jimenez-Castilla, Marisa Pardines, Iolanda Lazaro, Isabel Herrero del Real, Monica Flores-Muñoz, Jesus Egido, Oscar Lopez-Franco, and Carmen Gomez-Guerrero
Elsevier BV
Abril Ramírez-Higuera, Carolina Peña-Montes, Alejandra Barroso-Hernández, Óscar López-Franco, and Rosa María Oliart-Ros
Elsevier
Paulina E. Viveros-Watty, Oscar López-Franco, Rossana C. Zepeda, Gisela Aguirre, Juan C. Rodríguez-Alba, Manuel A. Gómez-Martínez, Lilia Castillo-Martínez, and Mónica Flores-Muñoz
Elsevier BV
Alejandra Barroso-Hernández, Abril Ramírez-Higuera, Carolina Peña-Montes, Sergio Alberto Cortés-Ramírez, Mauricio Rodríguez-Dorantes, Óscar López-Franco, and Rosa María Oliart-Ros
Informa UK Limited
ABSTRACT Introduction: Parkinson's disease (PD) is a chronic neurological disorder whose pathogenesis involves the loss of dopaminergic neurons and dopamine terminals, formation of Lewy bodies, and microgliosis. Its treatment includes dopamine-based drugs with limited results and adverse effects. Additionally, some neuroleptic drugs used for mental disorders produce side effects referred to as parkinsonism. Dietary interventions with ω-3 polyunsaturated fatty acids (ω-3 PUFA) have attracted attention since they play a key role in most of the processes associated with PD etiology. Objective: The purpose of our work was to investigate the effects of an ω-3 PUFA rich algal oil on locomotive alterations induced by haloperidol and D2 receptor protein and gene expression in Wistar rats. Methodology: Pre- and co-supplementation of algal oil (300 mg of ω-3 FA/kg/day for six weeks) and haloperidol (1.5 mg/kg/day for two weeks) were evaluated. Results: Haloperidol provoked locomotive alterations in the Open Field Test and a 43% diminution in D2 receptor in brain membranes; in pre-supplemented rats a 93% increase in D2 receptor protein expression and a partial maintenance of locomotory performance were observed, while in co-supplemented rats D2 receptor protein expression was maintained as in control rats, although locomotive behavior was found diminished as in haloperidol rats. Conclusions: These results confirm the beneficial effects of ω-3 PUFA over locomotory alterations and as neuroprotective and neurorestorative compounds and demonstrates a stimulatory action on D2 receptor presence, as a mechanism by which these fatty acids participate in brain health.
Óscar López-Franco, Jean-Pascal Morin, Albertina Cortés-Sol, Tania Molina-Jiménez, Diana I. Del Moral, Mónica Flores-Muñoz, Gabriel Roldán-Roldán, Claudia Juárez-Portilla, and Rossana C. Zepeda
Frontiers Media SA
[This corrects the article DOI: 10.3389/fnins.2021.579263.].
Óscar López-Franco, Jean-Pascal Morin, Albertina Cortés-Sol, Tania Molina-Jiménez, Diana I. Del Moral, Mónica Flores-Muñoz, Gabriel Roldán-Roldán, Claudia Juárez-Portilla, and Rossana C. Zepeda
Frontiers Media SA
Hepatic encephalopathy (HE) is one of the most disabling metabolic diseases. It consists of a complication of liver disease through the action of neurotoxins, such as excessive production of ammonia from liver, resulting in impaired brain function. Its prevalence and incidence are not well known, although it has been established that up to 40% of cirrhotic patients may develop HE. Patients with HE episodes display a wide range of neurological disturbances, from subclinical alterations to coma. Recent evidence suggests that the resolution of hepatic encephalopathy does not fully restore cognitive functioning in cirrhotic patients. Therefore, the aim of this review was to evaluate the evidence supporting the presence of lingering cognitive deficits in patients with a history of HE compared to patients without HE history and how liver transplant affects such outcome in these patients. We performed two distinct meta-analysis of continuous outcomes. In both cases the results were pooled using random-effects models. Our results indicate that cirrhotic patients with a history of HE show clear cognitive deficits compared to control cirrhotic patients (Std. Mean Difference (in SDs) = −0.72 [CI 95%: −0.94, −0.50]) and that these differences are not fully restored after liver transplant (Std. Mean Difference (in SDs) = −0.48 [CI 95%: −0.77, −0.19]).
Claudia Juárez-Portilla, Tatiana Olivares-Bañuelos, Tania Molina-Jiménez, José Armando Sánchez-Salcedo, Diana I. Del Moral, Thuluz Meza-Menchaca, Mónica Flores-Muñoz, Óscar López-Franco, Gabriel Roldán-Roldán, Arturo Ortega,et al.
Elsevier BV
K G Hernández-Flores, A L Calderón-Garcidueñas, G Mellado-Sánchez, R Ruiz-Ramos, L A Sánchez-Vargas, P Thomas-Dupont, I Y Izaguirre-Hernández, J Téllez-Sosa, J Martínez-Barnetche, L Wood,et al.
Oxford University Press (OUP)
SummaryListeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6–8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.
Mariano López-Franco, O. López-Franco, M. A. Murciano-Antón, M. Cañamero-Vaquero, M. J. Fernández-Aceñero, G. Herrero-Beaumont, and E. Gómez-Barrena
Springer Science and Business Media LLC
Carlota Recio, Ainhoa Oguiza, Beñat Mallavia, Iolanda Lazaro, Guadalupe Ortiz-Muñoz, Oscar Lopez-Franco, Jesus Egido, and Carmen Gomez-Guerrero
Springer Science and Business Media LLC
Beñat Mallavia, Ainhoa Oguiza, Oscar Lopez-Franco, Carlota Recio, Guadalupe Ortiz-Muñoz, Iolanda Lazaro, Virginia Lopez-Parra, Jesus Egido, and Carmen Gomez-Guerrero
Public Library of Science (PLoS)
Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fcγ receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in γ-chain (the common signaling subunit of activating Fcγ receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fcγ receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fcγ receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fcγ receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-κB activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fcγ receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fcγ receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fcγ receptor-mediated inflammatory responses could effectively suppress atherosclerosis.
Clive S. McKimmie, Mark D. Singh, Kay Hewit, Oscar Lopez-Franco, Michelle Le Brocq, Stefan Rose-John, Kit Ming Lee, Andrew H. Baker, Rachel Wheat, David J. Blackbourn,et al.
American Society of Hematology
Key PointsD6 regulates the ability of lymphatic endothelial cells to discriminate between mature and immature dendritic cells. D6 expression is regulated by inflammatory cytokines indicative of a preferential role in inflamed conditions.
Beñat Mallavia, Carlota Recio, Ainhoa Oguiza, Guadalupe Ortiz-Muñoz, Iolanda Lazaro, Virginia Lopez-Parra, Oscar Lopez-Franco, Susann Schindler, Reinhard Depping, Jesus Egido,et al.
Elsevier BV
Virginia Lopez-Parra, Beñat Mallavia, Oscar Lopez-Franco, Guadalupe Ortiz-Muñoz, Ainhoa Oguiza, Carlota Recio, Julia Blanco, Falk Nimmerjahn, Jesus Egido, and Carmen Gomez-Guerrero
Ovid Technologies (Wolters Kluwer Health)
Among patients with diabetes, increased production of immunoglobulins against proteins modified by diabetes is associated with proteinuria and cardiovascular risk, suggesting that immune mechanisms may contribute to the development of diabetes complications, such as nephropathy. We investigated the contribution of IgG Fcγ receptors to diabetic renal injury in hyperglycemic, hypercholesterolemic mice. We used streptozotocin to induce diabetes in apolipoprotein E-deficient mice and in mice deficient in both apolipoprotein E and γ-chain, the common subunit of activating Fcγ receptors. After 15 weeks, the mice lacking Fcγ receptors had significantly less albuminuria and renal hypertrophy, despite similar degrees of hyperglycemia and hypercholesterolemia, immunoglobulin production, and glomerular immune deposits. Moreover, diabetic Fcγ receptor-deficient mice had less mesangial matrix expansion, inflammatory cell infiltration, and collagen and α-smooth muscle actin content in their kidneys. Accordingly, expression of genes involved in leukocyte infiltration, fibrosis, and oxidative stress was significantly reduced in diabetic kidneys and in mesangial cells cultured from Fcγ receptor-deficient mice. In summary, preventing the activation of Fcγ receptors alleviates renal hypertrophy, inflammation, and fibrosis in hypercholesterolemic mice with diabetes, suggesting that modulating Fcγ receptor signaling may be renoprotective in diabetic nephropathy.
Julio Madrigal-Matute, Carlos Ernesto Fernandez-Garcia, Carmen Gomez-Guerrero, Oscar Lopez-Franco, Begoña Muñoz-Garcia, Jesus Egido, Luis Miguel Blanco-Colio, and Jose Luis Martin-Ventura
Oxford University Press (OUP)
AIMS
Reactive oxygen species (ROS) participate in atherogenesis through different mechanisms including oxidative stress and inflammation. Proteins implicated in both processes, such as mitogen-activated protein kinase kinase (MEK) and some NADPH oxidase (NOX) subunits, are heat shock protein-90 (HSP90) client proteins. In this work, we investigated the antioxidant properties of the HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in experimental atherosclerosis.
METHODS AND RESULTS
Treatment of ApoE(-/-) mice with 17-DMAG (2 mg/kg every 2 days for 10 weeks) decreased ROS levels and extracellular signal-regulated kinase (ERK) activation in aortic plaques compared with control animals. Accordingly, treatment of rat vascular smooth muscle cells (VSMCs) with 17-DMAG increased HSP27 and HSP70 and inhibited ERK activation. Interestingly, 17-DMAG diminished NADPH oxidase dependent ROS production in VSMCs and monocytes. In addition, a marked reduction in NADPH oxidase dependent ROS production was observed with HSP90siRNA and the opposite pattern with HSP70siRNA. 17-DMAG also diminished the expression of Nox1 and Nox organizer-1 (Noxo1) in VSMCs and monocytes. Interestingly, 17-DMAG was able to modulate ROS-induced monocyte to macrophage differentiation. Finally, higher expression of Nox1 and Noxo1 was found in the inflammatory region of human atherosclerotic plaques, colocalizing with VSMCs, macrophages, and ROS-producing cells.
CONCLUSION
Our results suggest that HSP90 inhibitors interfere with oxidative stress and modulate experimental atherosclerosis development through reduction in pro-oxidative factors.
Guadalupe Ortiz-Muñoz, Beñat Mallavia, Oscar Lopez-Franco, Purificacion Hernandez-Vargas, Jesus Egido, and Carmen Gomez-Guerrero
Humana Press
P. Fernandez-Vizarra, O. Lopez-Franco, B. Mallavia, A. Higuera-Matas, V. Lopez-Parra, G. Ortiz-Munoz, E. Ambrosio, J. Egido, O. F. X. Almeida, and C. Gomez-Guerrero
Oxford University Press (OUP)
Alzheimer's disease is a severely debilitating disease of high and growing proportions. Hypercholesterolaemia is a key risk factor in sporadic Alzheimer's disease that links metabolic disorders (diabetes, obesity and atherosclerosis) with this pathology. Hypercholesterolaemia is associated with increased levels of immunoglobulin G against oxidized lipoproteins. Patients with Alzheimer's disease produce autoantibodies against non-brain antigens and specific receptors for the constant Fc region of immunoglobulin G have been found in vulnerable neuronal subpopulations. Here, we focused on the potential role of Fc receptors as pathological players driving hypercholesterolaemia to Alzheimer's disease. In a well-established model of hypercholesterolaemia, the apolipoprotein E knockout mouse, we report increased brain levels of immunoglobulin G and upregulation of activating Fc receptors, predominantly of type IV, in neurons susceptible to amyloid β accumulation. In these mice, gene deletion of γ-chain, the common subunit of activating Fc receptors, prevents learning and memory impairments without influencing cholesterolaemia and brain and serum immunoglobulin G levels. These cognition-protective effects were associated with a reduction in synapse loss, tau hyperphosphorylation and intracellular amyloid β accumulation both in cortical and hippocampal pyramidal neurons. In vitro, activating Fc receptor engagement caused synapse loss, tau hyperphosphorylation and amyloid β deposition in primary neurons by a mechanism involving mitogen-activated protein kinases and β-site amyloid precursor protein cleaving enzyme 1. Our results represent the first demonstration that immunoglobulin G Fc receptors contribute to the development of hypercholesterolaemia-associated features of Alzheimer's disease and suggest a new potential target for slowing or preventing Alzheimer's disease in hypercholesterolaemic patients.
Mariano López-Franco, O. López-Franco, M. A. Murciano-Antón, M. Cañamero-Vaquero, G. Herrero-Beaumont, M. J. Fernández-Aceñero, and E. Gómez-Barrena
Springer Science and Business Media LLC
B. Munoz-Garcia, J. Madrigal-Matute, J. A. Moreno, J. L. Martin-Ventura, O. Lopez-Franco, C. Sastre, L. Ortega, L. C. Burkly, J. Egido, and L. M. Blanco-Colio
Oxford University Press (OUP)
AIMS
atherosclerotic plaque development can conclude with a thrombotic acute event triggered by plaque rupture/erosion. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumour necrosis factor superfamily that, through its receptor, fibroblast growth factor-inducible 14 (Fn14), participates in vascular remodelling, increasing vascular inflammatory responses and atherosclerotic lesion size in ApoE knockout mice. However, the role of the TWEAK-Fn14 axis in thrombosis has not been previously investigated.
METHODS AND RESULTS
we have examined whether TWEAK regulates expression of prothrombotic factors such as tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) in atherosclerotic plaques as well as in human aortic vascular smooth muscle cells (hASMCs) in culture. Expression of TF and PAI-1 was colocalized and positively correlated with Fn14 in human carotid atherosclerotic plaques. In vitro, TWEAK increased TF and PAI-1 mRNA, protein expression and activity in hASMCs. All these effects were reversed using blocking anti-TWEAK monoclonal antibody, anti-Fn14 antibody or Fn14 small interfering RNA, indicating that TWEAK increased the prothrombotic state through its receptor, Fn14. Finally, ApoE(-/-) mice were fed a hyperlipidaemic diet for 10 weeks, then randomized and treated with saline (controls), TWEAK (10 microg/kg/day), anti-TWEAK neutralizing monoclonal antibody (1000 µg/kg/day), or non-specific immunoglobulin G (1000 microg/kg/day) daily for 9 days. Systemic TWEAK injection increased TF and PAI-1 protein expression in the aortic root of ApoE(-/-) mice. Conversely, TWEAK blocking antibodies diminished both TF and PAI-1 protein expression compared with non-specific immunoglobulin G-treated mice.
CONCLUSIONS
our results indicate that the TWEAK-Fn14 axis can regulate activation of TF and PAI-1 expression in vascular cells. TWEAK-Fn14 may be a therapeutic target in the prothrombotic complications associated with atherosclerosis.
Guadalupe Ortiz-Muñoz, Virginia Lopez-Parra, Oscar Lopez-Franco, Paula Fernandez-Vizarra, Beñat Mallavia, Claudio Flores, Ana Sanz, Julia Blanco, Sergio Mezzano, Alberto Ortiz,et al.
Ovid Technologies (Wolters Kluwer Health)
Activation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) is an important mechanism by which hyperglycemia contributes to renal damage, suggesting that modulation of this pathway may prevent renal and vascular complications of diabetes. Here, we investigated the involvement of suppressors of cytokine signaling (SOCS) as intracellular negative regulators of JAK/STAT activation in diabetic nephropathy. In a rat model, inducing diabetes resulted in JAK/STAT activation and increased expression of SOCS1 and SOCS3. In humans, we observed increased expression of glomerular and tubulointerstitial SOCS proteins in biopsies of patients with diabetic nephropathy. In vitro, high concentrations of glucose activated JAK/STAT/SOCS in human mesangial and tubular cells. Overexpression of SOCS reversed the glucose-induced activation of the JAK/STAT pathway, expression of STAT-dependent genes (chemokines, growth factors, and extracellular matrix proteins), and cell proliferation. In vivo, intrarenal delivery of adenovirus expressing SOCS1 and SOCS3 to diabetic rats significantly improved renal function and reduced renal lesions associated with diabetes, such as mesangial expansion, fibrosis, and influx of macrophages. SOCS gene delivery also decreased the activation of STAT1 and STAT3 and the expression of proinflammatory and profibrotic proteins in the diabetic kidney. In summary, these results provide direct evidence for a link between the JAK/STAT/SOCS axis and hyperglycemia-induced cell responses in the kidney. Suppression of the JAK/STAT pathway by increasing intracellular SOCS proteins may have therapeutic potential in diabetic nephropathy.
Julio Madrigal-Matute, Oscar López-Franco, Luis Miguel Blanco-Colio, Begoña Muñoz-García, Priscila Ramos-Mozo, Luis Ortega, Jesus Egido, and Jose Luis Martín-Ventura
Oxford University Press (OUP)
AIMS
Heat shock protein 90 (HSP90) is a ubiquitous chaperone involved in the folding, activation, and assembly of many proteins. HSP90 inhibitors [17-allylamino-17-demethoxygeldamycin (17-AAG)/17-dimethyl aminothylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG)] bind to and inactivate HSP90, increasing the heat shock response and suppressing different signalling pathways. We aim to investigate the effect of HSP90 inhibitors in the modulation of inflammatory responses during atherogenesis.
METHODS AND RESULTS
In human atherosclerotic plaques, HSP90 immunostaining was increased in inflammatory regions and in plaques characterized by lower cap thickness. In cultured human macrophages and vascular smooth muscle cells, treatment with either 17-AAG or 17-DMAG increased HSP70 expression and reduced transcription factor [signal transducers and activators of transcription (STAT) and nuclear factor-kappaB (NF-kappaB)] activation and chemokine expression induced by proinflammatory cytokines. In vivo, hyperlipidaemic ApoE(-/-) mice were randomized to 17-DMAG (2 mg/kg every 2 days, n = 11) or vehicle injected (n = 9) during 10 weeks. Atherosclerotic plaques of mice treated with 17-DMAG displayed increased HSP70 expression and diminished NF-kappaB and STAT activation, along with decreased lesion, lipid, and macrophage content, compared with vehicle-injected mice. In addition, treatment with 17-DMAG significantly reduced monocyte chemoattractant protein-1 levels, both in plaques and in plasma.
CONCLUSION
HSP90 expression is associated with features of plaque instability in advanced human lesions. HSP90 inhibitors reduce inflammatory responses in atherosclerosis, suggesting that HSP90 could be a novel therapeutic target in atherosclerosis.
Begoña Muñoz-García, Juan Antonio Moreno, Oscar López-Franco, Ana Belén Sanz, José Luis Martín-Ventura, Julia Blanco, Aniela Jakubowski, Linda C. Burkly, Alberto Ortiz, Jesús Egido,et al.
Ovid Technologies (Wolters Kluwer Health)
Objective— Tumor necrosis factor–like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily of cytokines. TWEAK binds and activates the Fn14 receptor, and may regulate apoptosis, inflammation, and angiogenesis, in different pathological conditions. We have evaluated the effect of exogenous TWEAK administration as well as the role of endogenous TWEAK on proinflammatory cytokine expression and vascular and renal injury severity in hyperlipidemic ApoE-knockout mice. Methods and Results— ApoE −/− mice were fed with hyperlipidemic diet for 4 to 10 weeks, then randomized and treated with saline (controls), TWEAK (10 μg/kg/d), anti-TWEAK neutralizing mAb (1000 μg/kg/d), TWEAK plus anti-TWEAK antibody (10 μg TWEAK +1000 μg anti-TWEAK/kg/d), or nonspecific IgG (1000 μg/kg/d) daily for 9 days. In ApoE −/− mice, exogenous TWEAK administration in ApoE −/− mice induced activation of NF-κB, a key transcription factor implicated in the regulation of the inflammatory response, in vascular and renal lesions. Furthermore, TWEAK treatment increased chemokine expression (RANTES and MCP-1), as well as macrophage infiltration in atherosclerotic plaques and renal lesions. These effects were associated with exacerbation of vascular and renal damage. Conversely, treatment of ApoE −/− mice with an anti-TWEAK blocking mAb decreased NF-κB activation, proinflammatory cytokine expression, macrophage infiltration, and vascular and renal injury severity, indicating a pathological role for endogenous TWEAK. Finally, in murine vascular smooth muscle cells or tubular cells, either ox-LDL or TWEAK treatment increased expression and secretion of both RANTES and MCP-1. Furthermore, ox-LDL and TWEAK synergized for induction of MCP-1 and RANTES expression and secretion. Conclusion— Our results suggest that TWEAK exacerbates the inflammatory response associated with a high lipid–rich diet. TWEAK may be a novel therapeutic target to prevent vascular and renal damage associated with hyperlipidemia.
Julio Madrigal-Matute, Óscar López-Franco, Luis M. Blanco-Colio, Begoña Muñoz-García, Priscila Ramos-Mozo, Melany Van Oostrom, Olivier Meilhac, Jean-Baptiste Michel, Jesús Egido, and José L. Martín Ventura
Elsevier BV
Campbell G. Nicol, Laura Denby, Oscar Lopez-Franco, Rachel Masson, Crawford A. Halliday, Stuart A. Nicklin, Angelika Kritz, Lorraine M. Work, and Andrew H. Baker
Wiley
We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain‐selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies.
Guadalupe Ortiz-Muñoz, Jose Luis Martin-Ventura, Purificacion Hernandez-Vargas, Beñat Mallavia, Virginia Lopez-Parra, Oscar Lopez-Franco, Begoña Muñoz-Garcia, Paula Fernandez-Vizarra, Luis Ortega, Jesus Egido,et al.
Ovid Technologies (Wolters Kluwer Health)
Objective— Suppressors of cytokine signaling (SOCS) proteins are intracellular regulators of receptor signal transduction, mainly Janus kinase/signal transducers and activators of transcription (JAK/STAT). We investigated the effects of SOCS modulation on the JAK/STAT-dependent responses in vascular cells, and their implication in atherosclerotic plaque development. Methods and Results— Immunohistochemistry in human plaques revealed a high expression of SOCS1 and SOCS3 by vascular smooth muscle cells (VSMCs) and macrophages in the inflammatory region of the shoulders, when compared to the fibrous area. SOCS were also increased in aortic lesions from apoE −/− mice. In cultured VSMCs, endothelial cells, and monocytes, SOCS1 and SOCS3 were transiently induced by proinflammatory cytokines, proatherogenic lipoproteins, and immune molecules. Furthermore, overexpression of SOCS suppressed STAT activation and reduced inflammatory gene expression and cell growth, whereas SOCS knockdown increased these cell responses. In vivo, antisense oligodeoxynucleotides targeting SOCS3 exacerbated the atherosclerotic process in apoE −/− mice by increasing the size, leukocyte content, and chemokine expression in the lesions. Conclusions— SOCS expressed in atherosclerotic lesions are key regulators of vascular cell responses. Activation of this endogenous antiinflammatory pathway might be of interest in the treatment of atherosclerosis.