Maria Carmen Duran Ruiz | Universidad de Cadiz (original) (raw)
Papers by Maria Carmen Duran Ruiz
Free Radical Biology and Medicine
Journal of Leukocyte Biology, 2016
Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-lin... more Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins. We have previously found that the adaptor linker for activation of T cells, evolutionarily related to non-T cell activation linker, is cleaved upon proapoptotic stimuli in T lymphocytes and thymocytes, in a tyrosine phosphorylation-dependent fashion. Here, we describe non-T cell activation linker proteolytic cleavage triggered in human B cells and monocytes by Fas cross-linking and sta...
The Journal of cell biology, May 2, 2016
Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new pro... more Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs ba...
Polymers
The addition of natural substances with pharmacoactive properties to polymeric biomedical devices... more The addition of natural substances with pharmacoactive properties to polymeric biomedical devices would provide beneficial regarding the assimilation of these endoprostheses when implanted into a patient’s body. The added drug would facilitate endothelization by regulating the inflammatory processes that such interventions entail, preventing contamination hazards and favoring the angiogenesis or formation of blood vessels in the tissue. The present work used mango leaf extract (MLE) obtained through pressurized ethanol for this purpose. Polylactic acid (PLA) in the form of filaments or 3D-printed disks was impregnated by means of supercritical technology with MLE for the culture essays. The release kinetics has been studied and the polymer matrices have been examined by scanning electron microscopy (SEM). The impregnated devices were subjected to in vitro culture of colony-forming endothelial cells. The influence of the different impregnation conditions used for the production of th...
Molecular Therapy - Nucleic Acids
Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsol... more Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsolved, including the mechanisms of action of SARS-CoV-2 and which factors determine why individuals respond so differently to the viral infection. Herein, we performed an in silico analysis to identify host mi-croRNA targeting ACE2, TMPRSS2, and/or RAB14, all genes known to participate in viral entry and replication. Next, the levels of six microRNA candidates previously linked to viral and respiratory-related pathologies were measured in the serum of COVID-19-negative controls (n = 16), IgG-positive COVID-19 asymptomatic individuals (n = 16), and critical COVID-19 patients (n = 17). Four of the peripheral micro-RNAs analyzed (hsa-miR-32-5p, hsa-miR-98-3p, hsa-miR-423-3p, and hsa-miR-1246) were upregulated in COVID-19 critical patients compared with COVID-19-negative controls. Moreover, hsa-miR-32-5p and hsa-miR-1246 levels were also altered in critical versus asymptomatic individuals. Furthermore, these microRNA target genes were related to viral infection, inflammatory response, and coagulation-related processes. In conclusion, SARS-CoV-2 promotes the alteration of microRNAs targeting the expression of key proteins for viral entry and replication, and these changes are associated with disease severity. The microRNAs identified could be taken as potential biomarkers of COVID-19 progression as well as candidates for future therapeutic approaches against this disease.
Antioxidants
Cardiovascular diseases remain the leading cause of death worldwide, mainly triggered by the form... more Cardiovascular diseases remain the leading cause of death worldwide, mainly triggered by the formation of atherosclerotic plaques that reduce blood flow. Angiogenic cell therapy based on endothelial colony forming cells (ECFCs) constitutes a promising alternative to promote vascular revascularization; however, under the oxidative environment that prevails in ischemic areas, these cells become impaired. Thus, it is necessary to investigate strategies to enhance their regenerative properties. Antioxidant substances, such as polyphenols, have been shown to be useful for this purpose. In the current study we evaluated the potential of mango leaves, olive leaves and red grape pomace extracts, rich in polyphenols, to promote ECFC reparative effects. For this, aqueous and ethanolic extracts of the aforementioned raw materials were obtained by pressurized liquid extraction (PLE). After evaluating the polyphenol content and the antioxidant activity, in vitro assays were carried out, and we f...
Cells
The risk of complications following surgical procedures is significantly increased in patients wi... more The risk of complications following surgical procedures is significantly increased in patients with SARS-CoV-2 infection. However, the mechanisms underlying these correlations are not fully known. Spinal cord injury (SCI) patients who underwent reconstructive surgery for pressure ulcers (PUs) before and during the COVID-19 pandemic were included in this study. The patient’s postoperative progression was registered, and the subcutaneous white adipose tissue (s-WAT) surrounding the ulcers was analyzed by proteomic and immunohistochemical assays to identify the molecular/cellular signatures of impaired recovery. Patients with SCI and a COVID-19-positive diagnosis showed worse recovery and severe postoperative complications, requiring reintervention. Several proteins were upregulated in the adipose tissue of these patients. Among them, CKMT2 and CKM stood out, and CKM increased for up to 60 days after the COVID-19 diagnosis. Moreover, CKMT2 and CKM were largely found in MGCs within the ...
Molecular Medicine
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 mill... more Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential. Methods We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR −/IgG −, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG − (n:...
Stem Cell Research & Therapy
Background Endothelial colony forming cells (ECFCs), alone or in combination with mesenchymal ste... more Background Endothelial colony forming cells (ECFCs), alone or in combination with mesenchymal stem cells, have been selected as potential therapeutic candidates for critical limb-threatening ischemia (CLTI), mainly for those patients considered as “no-option,” due to their capability to enhance revascularization and perfusion recovery of ischemic tissues. Nevertheless, prior to translating cell therapy to the clinic, biodistribution assays are required by regulatory guidelines to ensure biosafety as well as to discard undesired systemic translocations. Different approaches, from imaging technologies to qPCR-based methods, are currently applied. Methods In the current study, we have optimized a cell-tracking assay based on DiR fluorescent cell labeling and near-infrared detection for in vivo and ex vivo assays. Briefly, an improved protocol for DiR staining was set up, by incubation of ECFCs with 6.67 µM DiR and intensive washing steps prior cell administration. The minimal signal de...
Frontiers in Cell and Developmental Biology
Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the tre... more Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the treatment of Chronic Limb-Threatening ischemia (CLTI), a disease characterized by extensive blockade of peripheral arteries, clinically presenting as excruciating pain at rest and ischemic ulcers which may lead to gangrene and amputation. BM-MNC implantation has shown to be efficient in promoting angiogenesis and ameliorating ischemic symptoms in CLTI patients. However, the variability seen between clinical trials makes necessary a further understanding of the mechanisms of action of BM-MNC, and moreover, to improve trial characteristics such as endpoints, inclusion/exclusion criteria or drug product compositions, in order to implement their use as stem-cell therapy.Materials: Herein, the effect of REX-001, a human-BM derived cell suspension enriched for mononuclear cells, granulocytes and CD34+ cells, has been assessed in a murine model of CLTI. In addition, a REX-001 placebo solution cont...
Cell Interaction - Molecular and Immunological Basis for Disease Management, 2021
Organoids have arisen as promising model systems in biomedical research and regenerative medicine... more Organoids have arisen as promising model systems in biomedical research and regenerative medicine due to their potential to reproduce the original tissue architecture and function. In the research field of cell–cell interactions, organoids mimic interactions taking place during organogenesis, including the processes that conduct to multi-lineage differentiation and morphogenetic processes, during immunology response and disease development and expansion. This chapter will address the basis of organoids origin, their importance on immune system cell–cell interactions and the benefits of using them in biomedicine, specifically their potential applications in regenerative medicine and personalized therapy. Organoids might represent a personalized tool for patients to receive earlier diagnoses, risk assessments, and more efficient treatments.
Antioxidants, 2021
Atherosclerosis remains the underlying process responsible for cardiovascular diseases and the hi... more Atherosclerosis remains the underlying process responsible for cardiovascular diseases and the high mortality rates associated. This chronic inflammatory disease progresses with the formation of occlusive atherosclerotic plaques over the inner walls of vascular vessels, with oxidative stress being an important element of this pathology. Oxidation of low-density lipoproteins (ox-LDL) induces endothelial dysfunction, foam cell activation, and inflammatory response, resulting in the formation of fatty streaks in the atherosclerotic wall. With this in mind, different approaches aim to reduce oxidative damage as a strategy to tackle the progression of atherosclerosis. Special attention has been paid in recent years to the transcription factor Nrf2 and its downstream-regulated protein heme oxygenase-1 (HO-1), both known to provide protection against atherosclerotic injury. In the current review, we summarize the involvement of oxidative stress in atherosclerosis, focusing on the role that...
Stem Cell Research & Therapy, 2020
Background Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arteri... more Background Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities. Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization. Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiog...
International Journal of Molecular Sciences, 2020
In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenito... more In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulin...
Journal of Proteomics, 2020
Journal of molecular and cellular cardiology, Apr 18, 2017
Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenera... more Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenerative medicine due to their assigned role in angiogenesis and vascular repair. In response to injury, EPCs promote vascular remodeling by replacement of damaged endothelial cells and/or by secreting angiogenic factors over the damaged tissue. Nevertheless, such mechanisms need to be further characterized. In the current approach we have evaluated the initial response of early EPCs (eEPCs) from healthy individuals after direct contact with the factors released by carotid arteries complicated with atherosclerotic plaques (AP), in order to understand the mechanisms underlying the neovascularization and remodeling properties assigned to these cells. Herein, we found that the AP secretome stimulated eEPCs proliferation and mobilization ex vivo, and such increase was accompanied by augmented permeability, cell contraction and also an increase of cell-cell adhesion in association with raised vin...
![Research paper thumbnail of [Performance of entero-insular axis in an athletic population: diet and exercise influence]](https://attachments.academia-assets.com/86535587/thumbnails/1.jpg)
](Nutrición hospitalaria, 2015
The relationship between physical exercise and appetite regulation can lead to improved competiti... more The relationship between physical exercise and appetite regulation can lead to improved competitive performance of athletes. Mediators of the entero-insular axis generate neurohumoral signals that influence on the appetite regulation and energy homeostasis. Determine the influence of diet and prolonged exercise on intestinal peptide, ghrelin, resistin, leptin, and incretins (GLP-1 and GIP) in an athlete population. It is a prospective intervention study, conducted from October 2012 to March 2013. 32 healthy semiprofessional rugby players, aged 13-39 years were included. Anthropometric measurements and blood samples were taken at time 0 and after six months of study. Athletes were randomized to a protein diet (PD) or Mediterranean diet (MD) and plasma levels of intestinal peptide, ghrelin, resistin, leptin, and incretins were calculated. In the PD group, GLP-1 and GIP plasmatic levels showed a significant decrease (p.
Free Radical Biology and Medicine
Journal of Leukocyte Biology, 2016
Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-lin... more Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins. We have previously found that the adaptor linker for activation of T cells, evolutionarily related to non-T cell activation linker, is cleaved upon proapoptotic stimuli in T lymphocytes and thymocytes, in a tyrosine phosphorylation-dependent fashion. Here, we describe non-T cell activation linker proteolytic cleavage triggered in human B cells and monocytes by Fas cross-linking and sta...
The Journal of cell biology, May 2, 2016
Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new pro... more Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs ba...
Polymers
The addition of natural substances with pharmacoactive properties to polymeric biomedical devices... more The addition of natural substances with pharmacoactive properties to polymeric biomedical devices would provide beneficial regarding the assimilation of these endoprostheses when implanted into a patient’s body. The added drug would facilitate endothelization by regulating the inflammatory processes that such interventions entail, preventing contamination hazards and favoring the angiogenesis or formation of blood vessels in the tissue. The present work used mango leaf extract (MLE) obtained through pressurized ethanol for this purpose. Polylactic acid (PLA) in the form of filaments or 3D-printed disks was impregnated by means of supercritical technology with MLE for the culture essays. The release kinetics has been studied and the polymer matrices have been examined by scanning electron microscopy (SEM). The impregnated devices were subjected to in vitro culture of colony-forming endothelial cells. The influence of the different impregnation conditions used for the production of th...
Molecular Therapy - Nucleic Acids
Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsol... more Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsolved, including the mechanisms of action of SARS-CoV-2 and which factors determine why individuals respond so differently to the viral infection. Herein, we performed an in silico analysis to identify host mi-croRNA targeting ACE2, TMPRSS2, and/or RAB14, all genes known to participate in viral entry and replication. Next, the levels of six microRNA candidates previously linked to viral and respiratory-related pathologies were measured in the serum of COVID-19-negative controls (n = 16), IgG-positive COVID-19 asymptomatic individuals (n = 16), and critical COVID-19 patients (n = 17). Four of the peripheral micro-RNAs analyzed (hsa-miR-32-5p, hsa-miR-98-3p, hsa-miR-423-3p, and hsa-miR-1246) were upregulated in COVID-19 critical patients compared with COVID-19-negative controls. Moreover, hsa-miR-32-5p and hsa-miR-1246 levels were also altered in critical versus asymptomatic individuals. Furthermore, these microRNA target genes were related to viral infection, inflammatory response, and coagulation-related processes. In conclusion, SARS-CoV-2 promotes the alteration of microRNAs targeting the expression of key proteins for viral entry and replication, and these changes are associated with disease severity. The microRNAs identified could be taken as potential biomarkers of COVID-19 progression as well as candidates for future therapeutic approaches against this disease.
Antioxidants
Cardiovascular diseases remain the leading cause of death worldwide, mainly triggered by the form... more Cardiovascular diseases remain the leading cause of death worldwide, mainly triggered by the formation of atherosclerotic plaques that reduce blood flow. Angiogenic cell therapy based on endothelial colony forming cells (ECFCs) constitutes a promising alternative to promote vascular revascularization; however, under the oxidative environment that prevails in ischemic areas, these cells become impaired. Thus, it is necessary to investigate strategies to enhance their regenerative properties. Antioxidant substances, such as polyphenols, have been shown to be useful for this purpose. In the current study we evaluated the potential of mango leaves, olive leaves and red grape pomace extracts, rich in polyphenols, to promote ECFC reparative effects. For this, aqueous and ethanolic extracts of the aforementioned raw materials were obtained by pressurized liquid extraction (PLE). After evaluating the polyphenol content and the antioxidant activity, in vitro assays were carried out, and we f...
Cells
The risk of complications following surgical procedures is significantly increased in patients wi... more The risk of complications following surgical procedures is significantly increased in patients with SARS-CoV-2 infection. However, the mechanisms underlying these correlations are not fully known. Spinal cord injury (SCI) patients who underwent reconstructive surgery for pressure ulcers (PUs) before and during the COVID-19 pandemic were included in this study. The patient’s postoperative progression was registered, and the subcutaneous white adipose tissue (s-WAT) surrounding the ulcers was analyzed by proteomic and immunohistochemical assays to identify the molecular/cellular signatures of impaired recovery. Patients with SCI and a COVID-19-positive diagnosis showed worse recovery and severe postoperative complications, requiring reintervention. Several proteins were upregulated in the adipose tissue of these patients. Among them, CKMT2 and CKM stood out, and CKM increased for up to 60 days after the COVID-19 diagnosis. Moreover, CKMT2 and CKM were largely found in MGCs within the ...
Molecular Medicine
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 mill... more Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential. Methods We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR −/IgG −, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG − (n:...
Stem Cell Research & Therapy
Background Endothelial colony forming cells (ECFCs), alone or in combination with mesenchymal ste... more Background Endothelial colony forming cells (ECFCs), alone or in combination with mesenchymal stem cells, have been selected as potential therapeutic candidates for critical limb-threatening ischemia (CLTI), mainly for those patients considered as “no-option,” due to their capability to enhance revascularization and perfusion recovery of ischemic tissues. Nevertheless, prior to translating cell therapy to the clinic, biodistribution assays are required by regulatory guidelines to ensure biosafety as well as to discard undesired systemic translocations. Different approaches, from imaging technologies to qPCR-based methods, are currently applied. Methods In the current study, we have optimized a cell-tracking assay based on DiR fluorescent cell labeling and near-infrared detection for in vivo and ex vivo assays. Briefly, an improved protocol for DiR staining was set up, by incubation of ECFCs with 6.67 µM DiR and intensive washing steps prior cell administration. The minimal signal de...
Frontiers in Cell and Developmental Biology
Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the tre... more Background: Bone Marrow Mononuclear Cells (BM-MNC) constitute a promising alternative for the treatment of Chronic Limb-Threatening ischemia (CLTI), a disease characterized by extensive blockade of peripheral arteries, clinically presenting as excruciating pain at rest and ischemic ulcers which may lead to gangrene and amputation. BM-MNC implantation has shown to be efficient in promoting angiogenesis and ameliorating ischemic symptoms in CLTI patients. However, the variability seen between clinical trials makes necessary a further understanding of the mechanisms of action of BM-MNC, and moreover, to improve trial characteristics such as endpoints, inclusion/exclusion criteria or drug product compositions, in order to implement their use as stem-cell therapy.Materials: Herein, the effect of REX-001, a human-BM derived cell suspension enriched for mononuclear cells, granulocytes and CD34+ cells, has been assessed in a murine model of CLTI. In addition, a REX-001 placebo solution cont...
Cell Interaction - Molecular and Immunological Basis for Disease Management, 2021
Organoids have arisen as promising model systems in biomedical research and regenerative medicine... more Organoids have arisen as promising model systems in biomedical research and regenerative medicine due to their potential to reproduce the original tissue architecture and function. In the research field of cell–cell interactions, organoids mimic interactions taking place during organogenesis, including the processes that conduct to multi-lineage differentiation and morphogenetic processes, during immunology response and disease development and expansion. This chapter will address the basis of organoids origin, their importance on immune system cell–cell interactions and the benefits of using them in biomedicine, specifically their potential applications in regenerative medicine and personalized therapy. Organoids might represent a personalized tool for patients to receive earlier diagnoses, risk assessments, and more efficient treatments.
Antioxidants, 2021
Atherosclerosis remains the underlying process responsible for cardiovascular diseases and the hi... more Atherosclerosis remains the underlying process responsible for cardiovascular diseases and the high mortality rates associated. This chronic inflammatory disease progresses with the formation of occlusive atherosclerotic plaques over the inner walls of vascular vessels, with oxidative stress being an important element of this pathology. Oxidation of low-density lipoproteins (ox-LDL) induces endothelial dysfunction, foam cell activation, and inflammatory response, resulting in the formation of fatty streaks in the atherosclerotic wall. With this in mind, different approaches aim to reduce oxidative damage as a strategy to tackle the progression of atherosclerosis. Special attention has been paid in recent years to the transcription factor Nrf2 and its downstream-regulated protein heme oxygenase-1 (HO-1), both known to provide protection against atherosclerotic injury. In the current review, we summarize the involvement of oxidative stress in atherosclerosis, focusing on the role that...
Stem Cell Research & Therapy, 2020
Background Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arteri... more Background Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities. Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization. Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiog...
International Journal of Molecular Sciences, 2020
In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenito... more In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulin...
Journal of Proteomics, 2020
Journal of molecular and cellular cardiology, Apr 18, 2017
Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenera... more Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenerative medicine due to their assigned role in angiogenesis and vascular repair. In response to injury, EPCs promote vascular remodeling by replacement of damaged endothelial cells and/or by secreting angiogenic factors over the damaged tissue. Nevertheless, such mechanisms need to be further characterized. In the current approach we have evaluated the initial response of early EPCs (eEPCs) from healthy individuals after direct contact with the factors released by carotid arteries complicated with atherosclerotic plaques (AP), in order to understand the mechanisms underlying the neovascularization and remodeling properties assigned to these cells. Herein, we found that the AP secretome stimulated eEPCs proliferation and mobilization ex vivo, and such increase was accompanied by augmented permeability, cell contraction and also an increase of cell-cell adhesion in association with raised vin...
Nutrición hospitalaria, 2015
The relationship between physical exercise and appetite regulation can lead to improved competiti... more The relationship between physical exercise and appetite regulation can lead to improved competitive performance of athletes. Mediators of the entero-insular axis generate neurohumoral signals that influence on the appetite regulation and energy homeostasis. Determine the influence of diet and prolonged exercise on intestinal peptide, ghrelin, resistin, leptin, and incretins (GLP-1 and GIP) in an athlete population. It is a prospective intervention study, conducted from October 2012 to March 2013. 32 healthy semiprofessional rugby players, aged 13-39 years were included. Anthropometric measurements and blood samples were taken at time 0 and after six months of study. Athletes were randomized to a protein diet (PD) or Mediterranean diet (MD) and plasma levels of intestinal peptide, ghrelin, resistin, leptin, and incretins were calculated. In the PD group, GLP-1 and GIP plasmatic levels showed a significant decrease (p.