95 research outputs found
Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO Mice: Comparison of intramuscular and intravenous administration
No full textRecombinant HDL Milano exerts greater anti-inflammatory and plaque stabilizing properties than HDL wild-type
No full textObjective: To verify the existence of association between plasma levels of pro- or anti-inflammatory mediators and atherosclerotic burden at coronary and carotid arteries in individuals aged of 80 or more years old.
Methods: Healthy individuals aged between 80 and 102 years old (n = 178) underwent evaluation of plasma cytokines and acute phase proteins, intima-media thickness (IMT) and presence of plaques in carotid arteries by ultrasound and coronary artery calcification (CAC) by cardiac computed tomography.
Results: There was no association between CAC and carotid plaques (p = 0.8), maximum (p = 0.06) or mean IMT (p = 0.2). No association was found between the presence of carotid plaques and CRP (p = 0.4), TNF-α (p = 0.8) or IL-10 (p = 0.2). Likewise, individuals in the first three quartiles for CRP, TNF-α or IL-10 had similar values of CAC, mean and maximum IMT. In contrast, individuals above the 75th percentile for CRP or for TNF-α had enhanced maximum IMT (p = 0.017 and p < 0.0001) and CAC (p = 0.026 and p = 0.01) and subjects with IL-10 levels above the 75th percentile had lower maximum IMT (p = 0.027) and CAC (p = 0.006) as compared with those below this percentile. There was no difference in mean IMT for individuals above or below the 75th percentile for CRP, TNF-α or IL-10.
Conclusion: In very old individuals, CAC and maximum IMT were positively associated with systemic inflammatory activity only in those above the 75th percentile. The markers of atherosclerotic burden at coronary and carotid arteries were not related to each other and were distinctly associated with pro- and anti-inflammatory mediators, suggesting that atherosclerosis development is different in these vascular beds
Synergistic effect of liver X receptor activation and simvastatin on plaque regression and stabilization: An magnetic resonance imaging study in a model of advanced atherosclerosis
No full textAging-associated oxidized albumin promotes cellular senescence and endothelial damage
No full textCarlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally to this work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damag
Sulodexida: potencial tratamiento contra el daño endotelial provocado por toxinas urémicas
No full textLas enfermedades cardiovasculares (ECV) son la principal causa de mortalidad en la enfermedad renal crónica (ERC). El desarrollo de ECV es consecuencia del daño endotelial provocado por la acumulación de toxinas urémicas, como el indoxil sulfato (IS) causado por la pérdida de la función renal. Las toxinas urémicas degradan el glicocálix endotelial, barrera fundamental que asegura la permeabilidad selectiva del endotelio. Su daño provoca la activación de una serie de vías oxidativas, proinflamatorias y, finalmente, la senescencia celular. La sulodexida (SDX) es un fármaco compuesto de glucosaminoglucanos que reparan el glicocálix. El objetivo fue evaluar el posible papel preventivo de la SDX sobre la disfunción endotelial inducida por IS. Se planteó un modelo in vitro de ERC con células endoteliales pretratadas con de SDX (0,5 ULP/mL), 48 horas y posteriormente, se indujo daño con IS (250 μM) a diferentes tiempos. Se valoró el espesor del glicocálix con WGA (Wheat Germ Agglutinin) y midiendo los niveles de expresión proteica y génica de sindecan-1. El estrés oxidativo se determinó valorando la presencia de especies reactivas de oxígeno (ROS) mediante la sonda DCFDA/H2DCFDA y la expresión proteica de enzimas antioxidantes como la superóxido dismutasa 1 (SOD1) y catalasa. La inflamación se evaluó valorando la fosforilación de p65 y midiendo la expresión de MCP-1, IL-6 e ICAM-1. La senescencia celular se determinó midiendo la actividad β-galactosidasa y por Western blot de p53. La SDX evitó el daño en el glicocálix producido por IS aunque sin diferencias significativas en sindecan-1. Además, tuvo lugar una reducción de la producción de ROS, sin observar cambios en SOD1 y catalasa. También el IS indujo un fenotipo proinflamatorio, así como senescencia celular, la cual parecía ser frenada por la SDX. Por tanto, se concluye que la SDX tiene potencial como tratamiento preventivo del daño endotelial asociado a la ERC.Máster Universitario en Dianas Terapéuticas en Señalización Celular: Investigación y Desarrollo (M132
Exploring New Kingdoms: The Role of Extracellular Vesicles in Oxi-Inflamm-Aging Related to Cardiorenal Syndrome
No full textThe incidence of age associated chronic diseases has increased in recent years. Although several diverse causes produce these phenomena, abundant evidence shows that oxidative stress plays a central role. In recent years, numerous studies have focused on elucidating the role of oxidative stress in the development and progression of both aging and chronic diseases, opening the door to the discovery of new underlying mechanisms and signaling pathways. Among them, senolytics and senomorphics, and extracellular vesicles offer new therapeutic strategies to slow the development of aging and its associated chronic diseases by decreasing oxidative stress. In this review, we aim to discuss the role of extracellular vesicles in human cardiorenal syndrome development and their possible role as biomarkers, targets, or vehicles of drugs to treat this syndrome.Instituto de Salud Carlos IIISociedad Española de NefrologíaMinisterio de Asuntos Económicos y Transformación DigitalMinisterio de Cultura y DeporteMinisterio de Ciencia e InnovaciónComunidad de Madri
Mitochondria: A new member involved in stem cell senescence. An extended commentary on 'Mitochondria pleiotropism in stem cell senescence: Mechanisms and therapeutic approaches by Mas-Bargues C. [Free Radic. Biol. Med. (2023) Nov 1;208:657-671. doi:10.1016/j.freeradbiomed.2023.09.019]'
No full textMitochondria: A new member involved in stem cell senescence. An extended commentary on 'Mitochondria pleiotropism in stem cell senescence: Mechanisms and therapeutic approaches by Mas-Bargues C. [Free Radic. Biol. Med. (2023) Nov 1;208:657-671. doi:10.1016/j.freeradbiomed.2023.09.019
Acute ApoA-I Milano administration induces plaque regression and stabilisation in the long term
No full textProteomic analysis of endothelial cells and extracellular vesicles in response to indoxyl sulfate: Mechanisms of endothelial dysfunction in chronic kidney disease
No full textCardiovascular pathology is the main cause of death in chronic kidney disease (CKD) patients. CKD is associated with the accumulation of uremic toxins in the bloodstream, and indoxyl sulfate (IS) is one of the most abundant uremic toxins found in the blood of CKD patients. We conducted an in vitro study to assess the mechanisms underlying the IS-induced endothelial dysfunction that could lead to cardiovascular diseases. We also studied their extracellular vesicles (EVs) owing to their capacity to act as messengers that transmit signals through their cargo.This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and cofounded by Fondo Europeo de Desarrollo Regional (FEDER): “PI19/00240”, “PI20/01321”, and “PI23/01109”. A.F. enjoyed the PFIS contract “FI20/00018” and F.M.S. a Sara Borrel “CD23/00049.” Also, G.V. received a contract from the Instituto de Investigación Sanitario del Hospital Universitario 12 de Octubre (i +12)“I +12-AY2OO414-1”. In addition, grants from Universidad de Alcalá (“Ayuda de la Línea de Actuación Excelencia para el Profesorado Universitario de la UAH”; EPU-INV-UAH/2022/001), RICORS2040; RD21/ 0005/0002 funded by European Union—NextGenerationEU and Comunidad de Madrid (CAM; P2022/BMD-7223 CIFRA_COR-CM),
supported this work.Peer reviewe
All-<it>trans </it>retinoic acid induces COX-2 and prostaglandin E<sub>2 </sub>synthesis in SH-SY5Y human neuroblastoma cells: involvement of retinoic acid receptors and extracellular-regulated kinase 1/2
No full textAbstract Background Our recent results show that all-trans retinoic acid (ATRA), an active metabolite of vitamin A, induces COX-dependent hyperalgesia and allodynia in rats. This effect was mediated by retinoic acid receptors (RARs) and was associated with increased COX-2 expression in the spinal cord. Since ATRA also up-regulated COX-2 expression in SH-SY5Y human neuroblastoma cells, the current study was undertaken to analyze in these cells the mechanism through which ATRA increases COX activity. Methods Cultured SH-SY5Y neuroblastoma cells were treated with ATRA. COX expression and kinase activity were analyzed by western blot. Transcriptional mechanisms were analyzed by RT-PCR and promoter assays. Pharmacological inhibitors of kinase activity and pan-antagonists of RAR or RXR were used to assess the relevance of these signaling pathways. Production of prostaglandin E2 (PGE2) was quantified by enzyme immunoabsorbent assay. Statistical significance between individual groups was tested using the non-parametric unpaired Mann-Whitney U test. Results ATRA induced a significant increase of COX-2 expression in a dose- and time-dependent manner in SH-SY5Y human neuroblastoma cells, while COX-1 expression remained unchanged. Morphological features of differentiation were not observed in ATRA-treated cells. Up-regulation of COX-2 protein expression was followed by increased production of PGE2. ATRA also up-regulated COX-2 mRNA expression and increased the activity of a human COX-2 promoter construct. We next explored the participation of RARs and mitogen-activated peptide kinases (MAPK). Pre-incubation of SH-SY5Y human neuroblastoma cells with either RAR-pan-antagonist LE540 or MAP kinase kinase 1 (MEK-1) inhibitor PD98059 resulted in the abolition of ATRA-induced COX-2 promoter activity, COX-2 protein expression and PGE2 production whereas the retinoid X receptor pan-antagonist HX531, the p38 MAPK inhibitor SB203580 or the c-Jun kinase inhibitor SP600125 did not have any effect. The increase in RAR-β expression and extracellular-regulated kinase 1/2(ERK1/2) phosphorylation in ATRA-incubated cells suggested that RARs and ERK1/2 were in fact activated by ATRA in SH-SY5Y human neuroblastoma cells. Conclusion These results highlight the importance of RAR-dependent and kinase-dependent mechanisms for ATRA-induced COX-2 expression and activity.</p
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