Grupos de investigación

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/19605

Browse

Now showing 1 - 20 of 1849

Remote ischemic conditioning protects against anthracycline cardiotoxicity without impairing its antitumor activity.
(SPRINGER, 2026-04) Díaz-Guerra, Anabel; Clemente-Moragón, Agustín; Pollán, Ángela; López-Palomar, Lucía; Cádiz, Laura; Ibáñez, Borja
Anthracyclines remain a cornerstone of treatment for many cancer types; however, their cardiotoxic potential leads to cardiac dysfunction in a substantial proportion of patients, ultimately compromising long-term quality of life. Few strategies have proven effective in preventing anthracycline-induced cardiotoxicity (AIC). Among them, remote ischemic conditioning (RIC) has emerged as one of the most promising, having shown robust cardioprotective potential in preclinical studies and currently being evaluated in clinical trials. However, it remains unclear whether this intervention, while protecting the heart, could also inadvertently protect tumors from the cytotoxic effects of anthracyclines, thereby reducing their antitumor efficacy. In this study, we investigated whether RIC protects against AIC in a tumor-bearing mouse model, allowing simultaneous assessment of both cardiac and tumoral responses. Cutaneous tumors were induced in CD1 mice using a DMBA/TPA protocol, followed by five weekly intraperitoneal injections of doxorubicin (5 mg/kg). Mice bearing tumors were randomized to receive doxorubicin alone or in combination with weekly RIC (three cycles of 5 min hindlimb ischemia/reperfusion). Longitudinal echocardiography was used to assess cardiac function, while tumor growth, survival, and body weight were monitored throughout the protocol. Doxorubicin treatment reduced overall survival, inhibited tumor growth, and induced left ventricular systolic dysfunction and cardiac atrophy compared with untreated controls. RIC preserved left ventricular ejection fraction, partially attenuated early left ventricular atrophy, and showed a trend towards improved survival, without attenuating the antitumor efficacy of doxorubicin, as tumor suppression remained comparable between treatment groups. These findings demonstrate that RIC preserves cardiac systolic function during anthracycline chemotherapy in tumor-bearing mice without impairing the antitumor efficacy of the drug. The results support RIC as a simple, safe, and low-cost non-pharmacological strategy to mitigate AIC with potential translational relevance for oncology patients.
Beta-blockers after invasively managed STEMI vs NSTEMI without reduced ejection fraction: a prespecified analysis from the REBOOT trial.
(EDICIONES DOYMA, 2026-04-23) Raposeiras-Roubín, Sergio; Anguita, Manuel; Latini, Roberto; Domínguez-Rodríguez, Alberto; Barrabés, José A; Sánchez, Pedro L; Ottani, Filippo; Pocock, Stuart; Owen, Ruth; Cristobo, Pablo; Gómez-Talavera, Sandra; Staszewsky, Lidia; Escalera, Noemí; Fernández-Vázquez, Felipe; Bianco, Matteo; Prada-Delgado, Óscar; Pérez-García, Carlos Nicolás; Pelizzoni, Valentina; Navarro, Felipe; Pérez-Rivera, José-Ángel; Martín-Gorria, Gonzalo; Vetrano, Alfredo; Fuster, Valentín; Rosselló, Xavier; Ibáñez, Borja
Recent trials have questioned the clinical benefit of beta-blockers in post-myocardial infarction (MI) patients with preserved left ventricular ejection fraction (LVEF). However, differences in pathophysiology and risk profile between MI with and without ST-segment elevation (STEMI and NSTEMI) may influence the effect of beta-blockers. In this prespecified subgroup analysis of the REBOOT trial, which randomized invasively managed MI patients with LVEF > 40% to beta-blockers or control, we evaluated differences in long-term effects of the intervention between STEMI (n = 4296) and NSTEMI (n = 4142). The primary endpoint was a composite of all-cause death, reinfarction, or heart failure hospitalization over a median follow-up of 3.7 years.
Progression of Established Atherosclerotic Lesions Is Not Inhibited by Endothelial Knockout of Caveolin-1-Brief Report.
(LIPPINCOTT WILLIAMS & WILKINS, 2026-02) Muñiz-Anquela, Rocío; Redondo-Angulo, Ibon; Lewis, Esmeralda A; Lolo, Fidel-Nicolás; González-Cintado, Leticia; Toledano-Donado, Mónica; Pulgarín-Alfaro, Marta; Del Pozo, Miguel A; Bentzon, Jacob Fog
Eradicating endothelial caveolae by deleting the (caveolin-1) gene reduces LDL (low-density lipoprotein) uptake in arteries and efficiently prevents early atherogenesis, but the role in established atherosclerosis is unknown. Here, to examine CAV1 as a potential therapeutic target, we deleted endothelial in mice after lesion development and analyzed the effect on LDL uptake and lesion progression. To allow timed endothelium-specific deletion, we generated male and female mice with floxed alleles and endothelium-specific inducible Cre recombinase. Atherosclerosis was induced by virus-mediated PCSK9 (proprotein convertase subtilisin/kexin type 9) gene transfer and a high-cholesterol diet. After 16 weeks of lesion development, endothelial deletion was induced by a series of tamoxifen injections, repeated after 4 weeks, and the mice were followed for another 4 weeks. Mice were injected with fluorescently labeled LDL at 1 and 18 hours before euthanasia to study uptake and retention in lesions. Sections of the aortic root were analyzed for lesion size, composition, and LDL accumulation. Efficient conditional knockout of endothelial was confirmed by CAV1 immunostaining and by the loss of caveolae by electron microscopy. Loss of endothelial for 8 weeks reduced LDL entry into lesions but did not significantly decrease LDL retention, lesion lipid accumulation, fibrous tissue, or lesion size. In males, a reduction in macrophages was seen. Targeting CAV1 does not efficiently block LDL entry or reduce lesion progression in established atherosclerosis. These findings open several questions for further research, including alternative LDL entry mechanisms that could circumvent caveolar transport in established atherosclerosis.
A comprehensive genetic catalog of human double-strand break repair.
(American Association for the Advancement of Science, 2025-10-02) de Alba, Ernesto López; Salguero, Israel; Giménez-Llorente, Daniel; Montes-Torres, Javier; Fernández-Sanromán, Ángel; Casajús-Pelegay, Ester; Terrón-Bautista, José; Barroso-González, Jonathan; Bernal, Juan A; Macintyre, Geoff; Fernández-Leiro, Rafael; Losada, Ana; Cortés-Ledesma, Felipe
The analysis of DNA sequence outcomes provides molecular insights into double-strand break (DSB) repair mechanisms. Using parallel in-pool profiling of Cas9-induced insertions and deletions (indels) within a genome-wide knockout library, we present a comprehensive catalog that assesses the influence of nearly every human gene on DSB repair outcomes. This REPAIRome resource uncovers uncharacterized mechanisms, pathways, and factors involved in DSB repair, including opposing roles for XLF and PAXX, a molecular explanation for Cas9-induced multinucleotide insertions, HLTF functions in Cas9-induced DSB repair, the involvement of the SAGA complex in microhomology-mediated end joining, and an indel mutational signature linked to VHL loss, renal carcinoma, and hypoxia. These results exemplify the potential of REPAIRome to drive future discoveries in DSB repair, CRISPR-Cas gene editing and the etiology of cancer mutational signatures.
Evolution in the Peri-Implant Oral Microbiome and Their Relationship to Long-Term Marginal Bone Loss: A Randomized Clinical Study.
(WILEY, 2025-07) Galindo-Moreno, Pablo; Gutierrez-Garrido, Lourdes; Duarte, Juan; Robles-Vera, Iñaki; Martin-Morales, Natividad; O'Valle, Francisco; Olaechea, Allinson; Carrillo-Galvez, Ana Belén; Padial-Molina, Miguel
To analyze the clinical, radiographic, and microbiological changes around implants with a multiphosphonate-treated surface, prosthetically loaded with two different protocols after 5 years of functional loading. A randomized clinical trial was designed to initiate prosthetic loading over single dental implants after 8 (control) or 4 weeks (test). Several variables were analyzed, including patients' level variables, intrasulcular biofilm, and marginal bone level at several time points, from 1 to 60 months after loading. A total of 23 patients attended the 5-year follow-up visit. No clinical variable changed over time, except mucosal thickness from dental impressions to prosthesis delivery. No significant radiographic differences were observed either over time or between groups. Microbiologically, there was a change in the microbiome from the constitution of the biological width to the final follow-up. Seven species changed significantly, with a significant increase in Porphyromonas gingivalis and Tannerella forsythia from 12 to 60 months and a decrease in the other species. However, changes in the relative abundance of species over time, whether increasing or decreasing, did not show a correlation with marginal bone loss. Implants with a multiphosphonate-treated surface showed no differences in clinical and radiographic variables after 5 years of function, regardless of the prosthetic loading protocol used. From a microbiological point of view, although there was an evolution of the microbiome in the peri-implant sulcus towards Socransky's red circle pathogenic bacteria, no microorganism showed a significant correlation with the radiographic changes produced in the peri-implant bone over time.
Chemical pollutant mixtures associated with metabolic health: Results from the European Health Examination Survey in Luxembourg.
(ELSEVIER, 2025-11-10) Martínez-Gómez, Jesús; Ciprián, Giovana M; Le Coroller, Gwenaëlle; Pexaras, Achilleas; Fernández-Jiménez, Rodrigo; Appenzeller, Brice M R; Ruiz-Castell, Maria
Metabolic syndrome (MetS) and its components -central obesity, hypertriglyceridemia, reduced levels of serum high-density cholesterol (HDL-c), high blood pressure (BP), and hyperglycemia- are highly prevalent worldwide. Classical modifiable risk factors and environmental ones, such as exposure to pollutants can contribute to these high prevalence rates. We assessed whether exposure to pollutant mixtures was associated with MetS and its components, identifying key contributing pollutants. We analyzed data from 606 adults aged 25-64 from the European Health Examination Survey (2013-2015). Among 152 analyzed chemicals, 40 were present in over 50 % of the samples and classified as flame retardants, industrial wastes, and plastics (4), insecticides (17), herbicides (12), and fungicides (7). Using weighted quantile sum regressions, we estimated associations of groups of pollutants and the total mixture with metabolic outcomes. Exposure to insecticides was associated with high BP, hyperglycemia, and hypertriglyceridemia; herbicides with abdominal obesity; and fungicides with MetS, hyperglycemia, and hypertriglyceridemia. The total mixture increased the odds of all outcomes, except low HDL-c [average OR = 2.06 (5th PCT = 1.23); average OR = 1.83 (5th PCT = 1.03); average OR = 2.42 (5th PCT = 1.42); average OR = 1.19 (5th PCT = 0.77); average OR = 2.15 (5th PCT = 1.37); average OR = 1.89 (5th PCT = 1.10)]. Prosulfocarb was a probable contributor to the mixture effect on MetS and abdominal obesity, ClCFCA on hypertriglyceridemia, and PNP on high BP. In conclusion, chemical pollutants are more present in individuals with metabolic derangements, with potentially stronger effects when combined. Reducing pesticide use, promoting safer alternatives, and creating protocols/regulatory standards for multiple-exposure scenarios are crucial for public health.
Insights into histone deacetylase inhibitors-induced cell death in cancer cell lines.
(Elsevier, 2025-10) Fuentes-Baile, María; García-Morales, Pilar; Pérez-Valenciano, Elizabeth; Mata-Balaguer, Trinidad; Menéndez-Gutiérrez, María P; de Juan Romero, Camino; Rodríguez-Lescure, Álvaro; Martín-Orozco, Elena; Mallavia, Ricardo; Barberá, Víctor M; Saceda, Miguel
Histone deacetylase inhibitors (HDACis) induce cell death in many chemoresistant cancer models, suggesting their potential as alternative treatments for these malignancies. However, their efficacy in solid tumors remains limited. Therefore, understanding the molecular mechanisms underlying HDACi-induced cell death is essential for developing targeted activators of these pathways, enabling the selective elimination of chemoresistant cancer cells while minimizing the widespread transcriptional effects of HDACis. In this study, we investigated HDACi-induced cell death across models of different cellular origins to determine whether a universal molecular mechanism triggers this process. Our findings demonstrate that HDACi-induced cell death is TP53-independent, resistant to caspase inhibitors, and sensitive to serine protease inhibitors. This form of cell death requires intracellular calcium mobilization to induce mitochondrial depolarization. Using DNA arrays, apoptosis protein arrays, and ELISA assays, combined with siRNA-mediated gene silencing, we identified genes with a causal relationship to TSA-induced cell death. These include dual-specificity phosphatases such as DUSP3 and DUSP10; endoplasmic reticulum stress-related genes such as XBP1, MBTPS1, MBTPS2, and RPS6KA5; and other genes like BAX, AIF, EAF2, NANOS1, and CCNYL1. Our findings reveal novel potential targets for developing antineoplastic agents designed to exploit HDACi-induced cell death pathways, providing a strategy to overcome chemoresistance in cancer therapy.
Fundamental Anatomy and Its Impact on Clinical Practice: Myocardial Bridging.
(Elsevier, 2025-10-15) Ortega-Pérez, Rodrigo; Ibañez, Borja; Sánchez-Quintana, Damián; Cabrera, José-Ángel
Understanding how long people with transthyretin amyloid cardiomyopathy (ATTR-CM) live when they take tafamidis as part of their regular healthcare: a plain language summary.
(TAYLOR & FRANCIS LTD, 2025-06) Garcia-Pavia, Pablo; Kristen, Arnt V; Drachman, Brian; Carlsson, Martin; Amass, Leslie; Maurer, Mathew S
This summary describes results from a called the ( for short). In this study from THAOS, researchers looked at people with a heart condition called ( for short). Some people from this study took an approved treatment for ATTR-CM called and some did not. Researchers looked at how many people with ATTR-CM were alive after two and a half years and three and a half years. They also looked at the people had when they took tafamidis.In people who took tafamidis, an estimated 8 in 10 people (84%) were alive after two and a half years, and an estimated 8 in 10 people (77%) were alive after three and a half years. In people who did not take tafamidis, an estimated 7 in 10 people (70%) were alive after two and a half years, and an estimated 6 in 10 people (59%) were alive after three and a half years. The side effects people had while taking tafamidis in the THAOS study were similar to what has been reported in clinical studies.This real-world study supports the use of tafamidis for improving survival in people with ATTR-CM[Box: see text].
Unraveling Comorbidities Contribution to Cardiac Diastolic Dysfunction and Heart Failure.
(LIPPINCOTT WILLIAMS & WILKINS, 2025-01) Villalba-Orero, María; López-Olañeta, Marina; Campos-Olmo, Belén; Jimenez-Carretero, Daniel; Sánchez, Lucía; Sánchez-Cabo, Fátima; Ausiello, Antonella; Cañas-Álvaro, Rodrigo; Camafeita, Emilio; Vázquez, Jesús; García-Pavía, Pablo; Pascual-Figal, Domingo; Lara-Pezzi, Enrique
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem characterized by multiple simultaneous comorbidities whose specific contribution is challenging to disentangle in humans, leading to a generalized therapeutic approach that may not account for the underlying pathology. We followed distinct mouse models of major HFpEF comorbidities for 2.5 years to unveil their specific contribution to the syndrome. All comorbidities contributed to HFpEF through partially distinct routes. Aging alone resulted in HFpEF in old age, with delayed left ventricular relaxation and kidney fibrosis. Obesity induced a faster deterioration of relaxation associated with enlarged left ventricle and liver fibrosis. Hypertension caused delayed ventricular relaxation independent from structural changes that preceded left atrial dilatation linked to aortic stiffness and increased fibrosis in myocardium and kidney. Chronic intermittent hypoxia led to HFpEF and relaxation impairment associated with pulmonary hypertension. Hyperglycemia accelerated diastolic dysfunction and HFpEF onset associated with reduced arterial flow and left ventricular remodeling. Therefore, the pathological substrates contributing to HFpEF included cardiac and noncardiac alterations with differential features for each comorbidity. Critically, the characteristics linked to diastolic dysfunction and HFpEF across the various comorbidities agreed with phenogroups observed in human patients. The identification of time-dependent pathological features provides a comprehensive picture of HFpEF progression associated with each comorbidity.
Identificación de ARN largos no codificantes aberrantemente expresados en células del músculo liso vascular en el síndrome de progeria de Hutchinson– Gilford
(2025-09-03) Peguero Jerez, Armando Gabriel; Andrés García, Vicente; Laura Francés, Javier; Lavin Plaza, Begoña
El síndrome de progeria de Hutchinson-Gilford (HGPS) es una enfermedad ultra rara causada por la expresión de progerina, una forma mutada de Lamin A, caracterizada por envejecimiento prematuro. Una de las principales características de la enfermedad es la disfunción de las células de muscula liso vascular (CMLV), las cuales sufren cambios fenotípicos que comprometen la estabilidad vascular. Evidencias recientes sugieren que los ARN largos no codificantes (lncRNAs) desempeñan funciones regulatorias en estos procesos; sin embargo, su papel en HGPS aún es desconocido. En este trabajo, reanalizamos dos bases de datos de secuenciación de RNA: 1) el análisis de ratones Apoe−/−LmnaG609G/G609G reveló 355 lncRNA con expresión aberrante, incluidos 49 no caracterizados anteriormente; y 2) el análisis de células de músculo liso de aorta humana (hAoSMCs) con expresión ectópica de progerina, donde se identificaron 633 lncRNA con expresión aberrante, incluidos 119 nuevos. Priorizamos el lncRNA Gm9991 (murino) y el lncGREM (humano), eleccionados por no haber sido descritos previamente y por su posible asociación con la disfunción de CMLVs en HGPS. Ambos lncRNAs fueron caracterizados parcialmente mediante chromosome walking, una estrategia de PCR que permite mapear regiones específicas de un transcrito. Estos análisis se realizaron en CMLVs con expresión inducible de progerina, las cuales mostraron cambios fenotípicos característicos de HGPS. Además, utilizamos VSMCs derivadas de iPSC de pacientes para cuantificar la expresión endógena de progerina. Este trabajo aporta bases sólidas para futuros estudios funcionales y establece modelos celulares para investigar el papel de los lncRNA en la disfunción de las CMLVs asociada al HGPS.
Obesity determines right ventricular subclinical dysfunction in middle-aged individuals
(OXFORD UNIV PRESS, 2025-11) Perez Garcia, C; Fuster, V; Garcia-Marti, G; Moreno-Arciniegas, A; Gomez-Talavera, S; Pizarro, G; Devesa, A; Oliva, B; Vazirani, R; Navarro-Guzman, A; Sanchez-Gonzalez, J; Bueno, H; Ibanez, B; Garcia-Lunar, I; Garcia-Alvarez, A
Abstract 4367883: Uptake of primary and secondary prevention against atherosclerotic disease in the Danish background population
(LIPPINCOTT WILLIAMS & WILKINS, 2025-11-04) Kragh, Maja Valentin; Hasselbalch, Rasmus; Perez-Garcia, Carlos Nicolás; Kunkel, Joakim; Garcia-Lunar, Ines; Eldrup, Nikolaj; Fuster, Jose; Bottcher, Morten; Iversen, Kasper; Kofoed, Klaus; Ibanez, Borja; Bundgaard, Henning
Effect of beta blockers in acute and chronic coronary syndromes without reduced ejection fraction: a landmark analysis from the REBOOT trial.
(Oxford University Press, 2026-02-27) Rossello, Xavier; Barrabés, José A; Piepoli, Massimo; Dominguez-Rodriguez, Alberto; Sánchez, Pedro L; Anguita, Manuel; Raposeiras-Roubín, Sergio; Grigis, Giulietta; Agüero, Jaume; Owen, Ruth; Pocock, Stuart; Pérez-García, Carlos Nicolás; Escalera, Noemí; Kallmeyer, Andrea; Sionis, Alessandro; Staszewsky, Lidia; Torres, Alfonso; Barquero, Rocio; Fernández-Vazquez, Felipe; Marín, Francisco; Vetrano, Alfredo; Pastor, Pablo; Fuster, Valentín; Latini, Roberto; Ibanez, Borja
Current guidelines recommend beta-blocker therapy after myocardial infarction (MI) regardless of left ventricular ejection fraction (LVEF). However, recent trials question their benefit in patients with preserved LVEF. No study has yet compared beta-blocker effects during the acute coronary syndrome (ACS) phase (≤1 year post-MI) vs. the chronic coronary syndrome (CCS) phase (>1 year). In this pre-specified landmark analysis of the REBOOT trial, we evaluated the effect of beta-blocker therapy on outcomes in two post-MI phases: the ACS period (first year; cohort 1, n = 8438) and the CCS period (>1 year, event-free patients with follow-up; cohort 2, n = 7783). The primary endpoint was all-cause death, nonfatal reinfarction, or heart failure hospitalization; secondary endpoints included individual and additional cardiovascular events. Among 623 primary outcome events, 238 occurred in the first year (28.9/1000 patient-years) and 385 thereafter (19.3/1000 patient-years). Secondary prevention use was generally high, but patients with early events had lower prescription rates than those with late events or no events. Beta-blockers were not associated with lower risk of the primary or component outcomes in either phase. A nonsignificant trend towards benefit of beta-blockers appeared during the first year in patients with mildly reduced LVEF (41-49%), whereas in the CCS phase, higher beta-blocker doses were associated with worse outcomes. In invasively treated MI patients with LVEF >40%, beta-blockers did not reduce adverse outcomes in either the ACS or CCS phases. These findings challenge their routine use in this population and support reconsidering current guidelines. Long-term beta-blocker users after MI may be candidates for deprescription.
Matrix metalloproteinases: new routes to the use of MT1-MMP as a therapeutic target in angiogenesis-related disease.
(BENTHAM SCIENCE PUBL LTD, 2007) Arroyo, A G; Genís, L; Gonzalo, P; Matías-Román, S; Pollán, A; Gálvez, B G
Angiogenesis, the formation of new vessels from pre-existing capillaries, is a fundamental physiological process which is also critical for the development of several pathological conditions; thus a diminished angiogenic response is related to ischemic disorders, whereas increased angiogenesis is associated with tumorigenesis and chronic inflammatory diseases. New ways of modulating angiogenesis therefore have potential in the treatment of these diseases. During angiogenesis, normally quiescent endothelial cells (ECs) become migratory and invade the surrounding tissue. To do this, they require a specific enzyme machinery to degrade the tissue barriers presented by the basement membranes and the interstitial matrix. This function is supplied by matrix metalloproteinase (MMP) proteins, a large family of enzymes responsible for degrading a variety of extracellular matrix (ECM) components and for modulating the bioactivity of transmembrane receptors and soluble factors. In this review we examine the participation of MMPs--in particular membrane type 1-matrix metalloproteinase (MT1-MMP)--in the different steps of angiogenesis, and discuss the mechanisms of regulation of MT1-MMP in ECs. Finally, we explore the potential use of MMP inhibitors (MMPI) in the treatment of angiogenesis-related disease, with especial emphasis on novel approaches to the inhibition of MT1-MMP activity in ECs.
KLRG1 identifies regulatory T cells with mitochondrial alterations that accumulate with aging.
(Nature Publishing Group, 2025-05) Soto-Heredero, Gonzalo; Gabandé-Rodríguez, Enrique; Carrasco, Elisa; Escrig-Larena, José Ignacio; Gómez de Las Heras, Manuel M; Delgado-Pulido, Sandra; Francos-Quijorna, Isaac; Blanco, Eva M; Fernández-Almeida, Álvaro; Abia, David; Rodríguez, María Josefa; Fernández-Díaz, Cristina M; Álvarez-Flores, María Beatriz; Ramírez de Molina, Ana; Jung, Sascha; Del Sol, Antonio; Zorita, Virginia; Sánchez-Cabo, Fátima; Torroja, Carlos; Mittelbrunn, María
Recent studies using single-cell RNA sequencing technology have uncovered several subpopulations of CD4 T cells that accumulate with aging. These age-associated T cells are emerging as relevant players in the onset of inflammaging and tissue senescence. Here, based on information provided by single-cell RNA sequencing data, we present a flow cytometry panel that allows the identification of age-associated T cell subsets in systematic larger analysis in mice. We use this panel to evaluate at the single-cell level mitochondrial and senescence marks in the different age-associated CD4 T cell subpopulations. Our analysis identifies a subpopulation of regulatory T (T) cells that is characterized by the extracellular expression of the co-inhibitory molecule killer cell lectin-like receptor subfamily G member 1 (KLRG1) and accumulates with aging in humans and mice. KLRG1-expressing T cells display senescence features such as mitochondrial alterations, increased expression of cell-cycle regulators and genomic DNA damage. Functionally, KLRG1 T cells show a reduced suppressive activity in vivo accompanied by a pro-inflammatory phenotype.
T-Cell Senescence in Human Metabolic Diseases.
(Korean Diabetes Association, 2024-09) Nga, Ha Thi; Nguyen, Thi Linh; Yi, Hyon-Seung
Immunosenescence denotes a state of dysregulated immune cell function characterized by a confluence of factors, including arrested cell cycle, telomere shortening, markers of cellular stress, mitochondrial dysfunction, loss of proteostasis, epigenetic reprogramming, and secretion of proinflammatory mediators. This state primarily manifests during the aging process but can also be induced in various pathological conditions, encompassing chronic viral infections, autoimmune diseases, and metabolic disorders. Age-associated immune system alterations extend to innate and adaptive immune cells, with T-cells exhibiting heightened susceptibility to immunosenescence. In particular, senescent T-cells have been identified in the context of metabolic disorders such as obesity, diabetes, and cardiovascular diseases. Recent investigations suggest a direct link between T-cell senescence, inflammation, and insulin resistance. The perturbation of biological homeostasis by senescent T-cells appears intricately linked to the initiation and progression of metabolic diseases, particularly through inflammation-mediated insulin resistance. Consequently, senescent T-cells are emerging as a noteworthy therapeutic target. This review aims to elucidate the intricate relationship between metabolic diseases and T-cell senescence, providing insights into the potential roles of senescent T-cells in the pathogenesis of metabolic disorders. Through a comprehensive examination of current research findings, this review seeks to contribute to a deeper understanding of the complex interplay between immunosenescence and metabolic health.
Immune profiling of cancer patients in the Spanish Immunotherapy Registry of Cardiovascular Toxicity (SIR-CVT)
(Oxford University Press, 2025-08-01) Martin, P; Ortega-Sollero, E; Ruiz-Fernandez, I; Zatarain Nicolas, E; Marquez-Roda, I; De Castro Carpeno, J; Martin Garcia, A; Lozano Palencia, T; Mitroi, C; Moliner Borja, P; Pernas, S; Alva Blanchi, M; Jimenez Lopez-Guarch, C; Toccheti, C G; Lopez-Fernandez, T
ERC-funded proof of concept grant: targeting imidazoline 1-receptor in atherosclerosis.
(OXFORD UNIV PRESS, 2026-03-09) Mastrangelo, Annalaura; Robles-Vera, Iñaki; Sancho, David
Interferon stimulated gene 15 (ISG15) modulates phenotype of vascular smooth muscle cells and pathological vascular remodeling.
(DOYMA, 2025) Soudant, Julius; González-Blázquez, Raquel; Merino, Abraham; Ballesteros-Martínez, Constanza; Rodrigues-Diez, Raquel; Moreno-Carriles, Rosa; Nistal, J Francisco; Guerra, Susana; Redondo, Juan Miguel; Salaices, Mercedes; Briones, Ana M; García-Redondo, Ana B
Inflammation is a major determinant of abdominal aortic aneurysms (AAA). Interferon stimulated gene 15 (ISG15) has a role in vascular remodelling in AAA. This study investigates the mechanisms whereby ISG15 might affect vascular remodeling and function. We used vascular smooth muscle cells (VSMC) from wild type (ISG15) o ISG15 knockout (ISG15) mice, aorta from ISG15 and ISG15 mice infused with angiotensin II (1.44mg/kg/day, sc, 14 days), and human AAA. We also performed a model of recombinant ISG15 infusion (rISG15, sc, 100 and 500ng/day, 14 days) in mice. In VSMC, ISG15 deficiency increased the expression of contractile (Acta2, Tagln) and synthetic (Fn1, Col1a2, Col3, Col4) markers and decreased the expression of the calcification marker Spp1. Ang II infusion changed the expression of phenotype markers differently in aorta from ISG15 or ISG15 mice. ISG15 expression showed a negative correlation with expression of contractile markers (ACTA2, CNN1), and with COL3a1, in human samples from patients with AAA or with stenotic aorto-iliac pathology. rISG15 infusion induced hypotrophic vascular remodelling in mesenteric arteries without affecting vascular mechanics. Aorta of ISG15 mice contracted more to thromboxane A analogue U46619, compared to ISG15mice. Both aorta and mesenteric arteries from rISG15-treated mice showed less contractility than control mice. ISG15 participates in pathological vascular remodeling probably by modulating VSMC phenotype. These changes could also impact in the vascular function.

Browse

Recent Submissions