Person: Moreno GutiƩrrez, Laura
Loading...
First Name
Laura
Last Name
Moreno GutiƩrrez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
FarmacologĆa y ToxicologĆa
Area
FarmacologĆa
Identifiers
22 results
Search Results
Now showing 1 - 10 of 22
Item Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma(Cancers, 2021) Ortiz Ruiz, Alejandra; Ruiz Heredia, Yanira; Morales, MarĆa Luz; Aguilar Garrido, Pedro; GarcĆa Ortiz, Almudena; Valeri Lozano, Antonio; BĆ”rcena Asensio, Carmen; GarcĆa MartĆn, Rosa MarĆa; Garrido, Vanesa; Moreno GutiĆ©rrez, Laura; Gimenez, Alicia; Navarro Aguadero, Miguel Ćngel; Velasco EstĆ©vez, MarĆa; Lospitao, Eva; Cedena, MarĆa Teresa; Barrio, Santiago; MartĆnez LĆ³pez, JoaquĆn; Linares GĆ³mez, MarĆa; Gallardo, MiguelMitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.Item Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension(Journal of Clinical Medicine, 2020) Callejo Arranz, MarĆa; Mondejar ParreƱo, Gema; Esquivel Ruiz, Sergio Antonio; Olivencia Plaza, Miguel Ćngel; Moreno GutiĆ©rrez, Laura; Blanco, Isabel; Escribano SubĆas, MarĆa Pilar; Cogolludo Torralba, Ćngel Luis; Barbera, Joan Albert; PĆ©rez VizcaĆno, FranciscoIntroduction: Epidemiological studies suggest a relationship between vitamin D deficiency and cardiovascular and respiratory diseases. However, whether total, bioavailable, and/or free vitamin D levels have a prognostic role in pulmonary arterial hypertension (PAH) is unknown. We aimed to determine total, bioavailable, and free 25-hydroxy-vitamin D (25(OH)vitD) plasma levels and their prognostic value in PAH patients. Methods: In total, 67 samples of plasma from Spanish patients with idiopathic, heritable, or drug-induced PAH were obtained from the Spanish PH Biobank and compared to a cohort of 100 healthy subjects. Clinical parameters were obtained from the Spanish Registry of PAH (REHAP). Results: Seventy percent of PAH patients had severe vitamin D deficiency (total 25(OH)vitD < 10 ng/mL) and secondary hyperparathyroidism. PAH patients with total 25(OH)vitD plasma above the median of this cohort (7.17 ng/mL) had better functional class and higher 6-min walking distance and TAPSE (tricuspid annular plane systolic excursion). The main outcome measure of survival was significantly increased in these patients (age-adjusted hazard ratio: 5.40 (95% confidence interval: 2.88 to 10.12)). Vitamin D-binding protein (DBP) and albumin plasma levels were downregulated in PAH. Bioavailable 25(OH)vitD was decreased in PAH patients compared to the control cohort. Lower levels of bioavailable 25(OH)vitD (<0.91 ng/mL) were associated with more advanced functional class, lower exercise capacity, and higher risk of mortality. Free 25(OH)vitD did not change in PAH; however, lower free 25(OH)vitD (<1.53 pg/mL) values were also associated with high risk of mortality. Conclusions: Vitamin D deficiency is highly prevalent in PAH, and low levels of total 25(OH)vitD were associated with poor prognosis.Item Kv7 channels critically determine coronary artery reactivity: left-right differences and down-regulation by hyperglycaemia(Cardiovascular Research, 2015) Morales Cano, Daniel; Moreno GutiĆ©rrez, Laura; Barreira, Bianca; Pandolfi, Rachele; Chamorro, Virginia; Jimenez, Rosario; Villamor, Eduardo; Duarte, Juan; PĆ©rez VizcaĆno, Francisco; Cogolludo Torralba, Ćngel LuisAims Voltage-gated potassium channels encoded by KCNQ genes (Kv7 channels) are emerging as important regulators of vascular tone. In this study, we analysed the contribution of Kv7 channels to the vasodilation induced by hypoxia and the cyclic AMP pathway in the coronary circulation. We also assessed their regional distribution and possible impairment by diabetes. Methods and results We examined the effects of Kv7 channel modulators on K+ currents and vascular reactivity in rat left and right coronary arteries (LCAs and RCAs, respectively). Currents from LCA were more sensitive to Kv7 channel inhibitors (XE991, linopirdine) and activators (flupirtine, retigabine) than those from RCA. Accordingly, LCAs were more sensitive than RCAs to the relaxation induced by Kv7 channel enhancers. Likewise, relaxation induced by the adenylyl cyclase activator forskolin and hypoxia, which were mediated through Kv7 channel activation, were greater in LCA than in RCA. KCNQ1 and KCNQ5 expression was markedly higher in LCA than in RCA. After incubation with high glucose (HG, 30 mmol/L), myocytes from LCA, but not from RCA, were more depolarized and showed reduced Kv7 currents. In HG-incubated LCA, the effects of Kv7 channel modulators and forskolin were diminished, and the expression of KCNQ1 and KCNQ5 was reduced. Finally, vascular responses induced by Kv7 channel modulators were impaired in LCA, but not in RCA, from type 1 diabetic rats. Conclusion Our results reveal that the high expression and function of Kv7 channels in the LCA and their down-regulation by diabetes critically determine the sensitivity to key regulators of coronary tone.- Project number: 273
Item ElaboraciĆ³n de casos clĆnicos para el aprendizaje basado en casos prĆ”cticos: una herramienta pedagĆ³gica para la inmersiĆ³n en la materia de profesores noveles y un recurso didĆ”ctico en la metodologĆa de aprendizaje con participaciĆ³n del estudiante(2023) GutiĆ©rrez LĆ³pez, MarĆa Dolores; Caballero Collado, Ricardo; Caso, Javier; DelpĆ³n Mosquera, MarĆa Eva; GarcĆa Bueno, Borja; Leza Cerro, Juan Carlos; Lizasoain, Ignacio; McDowell Mata, Karina; Morales, Daniel; Moreno GutiĆ©rrez, Laura; MuƱoz Madrigal, Jose Luis; OāShea Gaya, MarĆa Esther; PĆ©rez VizcaĆno, Francisco; Tejerina Maria, Teresa; Vidal Casado, Rebeca; Vidal, Alfonso; MartĆn HernĆ”ndez, David; Malan-MĆ¼ller, Stefanie; Olivencia, Miguel Ćngel; Morales, Nuria; NĆŗƱez de la Calle, Carlos; Vicente Crespo, Maria Elena; Cogolludo Torralba, Ćngel LuisEl proyecto propone la elaboraciĆ³n de nuevos casos clĆnicos que asemejen situaciones reales sobre los que los estudiantes puedan desarrollar un aprendizaje autĆ³nomo dirigido por el profesorado en funciĆ³n de los conceptos que sean de interĆ©s para cada grupo farmacolĆ³gico y acercĆ”ndole a la situaciĆ³n mĆ”s cercana a su prĆ”ctica profesional. Los objetivos del proyecto son: 1) Generar una base de nuevos casos clĆnicos dirigidos a que los estudiantes trabajen sobre grupos de fĆ”rmacos en un contexto lo mĆ”s real posible. Los diferentes casos que se elaboren en este proyecto podrĆ”n ser utilizados en la docencia de diversas asignaturas impartidas por miembros del departamento de FarmacologĆa y ToxicologĆa. Las sesiones dirigidas al estudio basado en la resoluciĆ³n de casos se plantean como una herramienta docente que tiene como finalidad el desarrollo de competencias transversales como promover la motivaciĆ³n, el trabajo en equipo, la participaciĆ³n de los estudiantes en los debates, asĆ como, fomentar el pensamiento crĆtico y el conocimiento del mĆ©todo cientĆfico. Este tipo de aprendizaje en contexto facilita la integraciĆ³n de los conocimientos y su mayor retenciĆ³n ademĆ”s de la dotar a los estudiantes con las habilidades para fomentar un aprendizaje continuo. 2) Apoyar la formaciĆ³n del profesorado de reciente incorporaciĆ³n, asĆ como del personal investigador que participan como colabores en tareas docentes del departamento y que podrĆan ser potenciales futuros docentes. Item Ceramide and Regulation of Vascular Tone(International Journal of Molecular Sciences, 2019) Cogolludo Torralba, Ćngel Luis; Villamor, Eduardo; PĆ©rez VizcaĆno, Francisco; Moreno GutiĆ©rrez, LauraIn addition to playing a role as a structural component of cellular membranes, ceramide is now clearly recognized as a bioactive lipid implicated in a variety of physiological functions. This review aims to provide updated information on the role of ceramide in the regulation of vascular tone. Ceramide may induce vasodilator or vasoconstrictor effects by interacting with several signaling pathways in endothelial and smooth muscle cells. There is a clear, albeit complex, interaction between ceramide and redox signaling. In fact, reactive oxygen species (ROS) activate different ceramide generating pathways and, conversely, ceramide is known to increase ROS production. In recent years, ceramide has emerged as a novel key player in oxygen sensing in vascular cells and mediating vascular responses of crucial physiological relevance such as hypoxic pulmonary vasoconstriction (HPV) or normoxic ductus arteriosus constriction. Likewise, a growing body of evidence over the last years suggests that exaggerated production of vascular ceramide may have detrimental effects in a number of pathological processes including cardiovascular and lung diseases.Item Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion(Molecules, 2016) Chamorro, Virginia; Pandolfi, Rachele; Moreno GutiĆ©rrez, Laura; Barreira, Bianca; MartĆnez-Ramas, Andrea; Morales Cano, Daniel; Ruiz-Cabello, JesĆŗs; Lorente, JosĆ©; Duarte, Juan; Cogolludo Torralba, Ćngel Luis; Ćlvarez-Sala Walther, Jose Luis; PĆ©rez VizcaĆno, FranciscoBackground: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. Results: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 KaplanāMeier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. Conclusions: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion.Item Restoration of Vitamin D Levels Improves Endothelial Function and Increases TASK-Like K+ Currents in Pulmonary Arterial Hypertension Associated with Vitamin D Deficiency(Biomolecules, 2021) Callejo Arranz, MarĆa; Morales Cano, Daniel; Mondejar ParreƱo, Gema; Barreira, Bianca; Esquivel Ruiz, Sergio Antonio; Olivencia Plaza, Miguel Ćngel; Moreno GutiĆ©rrez, Laura; Cogolludo Torralba, Ćngel Luis; PĆ©rez VizcaĆno, FranciscoVitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We hypothesize that recovering optimal levels of vitD in an animal model of PAH previously depleted of vitD improves the hemodynamics, the endothelial dysfunction and the ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and randomly divided into two groups: (a) continued on vitD-free diet or (b) received an oral dose of 100,000 IU/Kg of vitD plus standard diet for three weeks. Hemodynamics, pulmonary vascular remodeling, pulmonary arterial contractility, and K+ currents were analyzed. Results: Recovering optimal levels of vitD improved endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the activity of TASK-1 potassium channels. However, vitD supplementation did not reduce pulmonary pressure and did not ameliorate pulmonary vascular remodeling and right ventricle hypertrophy. Conclusions: Altogether, these data suggest that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH.Item HIV transgene expression impairs K+ channel function in the pulmonary vasculature(American Journal of Physiology - Lung Cellular and Molecular Physiology, 2018) Mondejar ParreƱo, Gema; Morales Cano, Daniel; Barreira, Bianca; Callejo, Maria; Ruiz-Cabello Osuna, JesĆŗs; Moreno GutiĆ©rrez, Laura; Esquivel Ruiz, Sergio Antonio; Mathie, Alistair; Butrous, Ghazwan; PĆ©rez VizcaĆno, Francisco; Cogolludo Torralba, Ćngel LuisHuman immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH); however, the pathogenesis of HIV-related PAH remains unclear. Since K+ channel dysfunction is a common marker in most forms of PAH, our aim was to analyze whether the expression of HIV proteins is associated with impairment of K+ channel function in the pulmonary vascular bed. HIV transgenic mice (Tg26) expressing seven of the nine HIV viral proteins and wild-type (WT) mice were used. Hemodynamic assessment was performed by echocardiography and catheterization. Vascular reactivity was studied in endothelium-intact pulmonary arteries. K+ currents were recorded in freshly isolated pulmonary artery smooth muscle cells (PASMC) using the patch-clamp technique. Gene expression was assessed using quantitative RT-PCR. PASMC from Tg26 mice had reduced K+ currents and were more depolarized than those from WT. Whereas voltage-gated K+ channel 1.5 (Kv1.5) currents were preserved, pH-sensitive noninactivating background currents (IKN) were nearly abolished in PASMC from Tg26 mice. Tg26 mice had reduced lung expression of Kv7.1 and Kv7.4 channels and decreased responses to the Kv7.1 channel activator L-364,373 assessed by vascular reactivity and patch-clamp experimental approaches. Although we found pulmonary vascular remodeling and endothelial dysfunction in Tg26 mice, this was not accompanied by changes in hemodynamic parameters. In conclusion, the expression of HIV proteins in vivo impairs pH-sensitive IKN and Kv7 currents. This negative impact of HIV proteins in K+ channels was not sufficient to induce PAH, at least in mice, but may play a permissive or accessory role in the pathophysiology of HIV-associated PAH.- Project number: 131
Item Plan de formaciĆ³n docente de jĆ³venes investigadores pre- y postdoctorales del Departamento de FarmacologĆa y ToxicologĆa.(2019) O'Shea Gaya, MarĆa Esther; PĆ©rez Vizcaino, Francisco; Aleixandre De ArtiƱano, MarĆa Amaya; Caballero Collado, Ricardo; Cogolludo Torralba, Ćngel Luis; Delpon Mosquera, MarĆa Eva; GutiĆ©rrez LĆ³pez, MarĆa Dolores; Lizasoain HernĆ”ndez, Ignacio; Moro SĆ”nchez, MarĆa Ćngeles; Tejerina SĆ”nchez, MarĆa Teresa; Tamargo MenĆ©ndez, JuĆ”n; Moreno GutiĆ©rrez, Laura; Vicente Crespo, MarĆa Elena; GimĆ©nez GĆ³mez, Pablo; Ulecia MorĆ³n, Cristina; Callejo Arranz, MarĆa; Medina Alonso, Violeta; GarcĆa Utrilla, RaquelLos objetivos que se han alcanzado son los siguientes: 1. Teniendo en cuenta los resultados obtenidos durante el curso 2018-19 (ademĆ”s de los resultados obtenidos en el curso 2017-18) los participantes han alcanzado una formaciĆ³n por encima de lo esperado en FarmacologĆa habiendo asistido a una media de 57% del curso en su primer aƱo de participaciĆ³n (cuando lo estipulado en el Plan de Formacion Docente es del 30%). AdemĆ”s, han superado un 42,3% de la materia entre su primer y segundo aƱo con una calificaciĆ³n media de 8,3. 2. Los jĆ³venes investigadores han realizado una media de 10 horas de prĆ”cticas docentes contabilizando aquellas dedicadas a la asistencia a prĆ”cticas como oyentes, el ensayo de las prĆ”cticas con tutores y la imparticiĆ³n misma de las sesiones de prĆ”cticas. El nĆŗmero de horas estĆ” muy limitado por el bajo nĆŗmero de horas prĆ”cticas en las asignaturas de FarmacologĆa del Dpto. y el elevado nĆŗmero de jĆ³venes investigadores incorporados al Dpto. 3. Con todo lo anterior, los jĆ³venes investigadores han alcanzado la formaciĆ³n en competencias docentes y las horas realizadas han sido acreditadas a las respectivas autoridades de sus becas/contratos. Su participaciĆ³n en la docencia prĆ”ctica les permitirĆ” en el futuro solicitar un certificado de actividades docentes emitido por las autoridades acadĆ©micas de la Facultad de Medicina que avalaran su experiencia docente en solicitudes de acreditaciĆ³n a las diferentes figuras de profesor ante la ANECA. AdemĆ”s, el Dpto. de FarmacologĆa y ToxicologĆa ha emitido informes detallados de Aptitud Docente en FarmacologĆa reflejando su participaciĆ³n en el Plan de FormaciĆ³n Docente del Dpto. que podrĆ”n ser consideradas en solicitudes a puestos docentes en el futuro. Item Ceramide Mediates Acute Oxygen Sensing in Vascular Tissues(Antioxidants and Redox Signaling, 2014) Moreno GutiĆ©rrez, Laura; Moral Sanz, Javier; Morales Cano, Daniel; Barreira, Bianca; Moreno, Enrique; Ferrarini, Alessia; Pandolfi, Rachele; Ruperez, Francisco J.; Cortijo, Julio; SĆ”nchez Luna, Manuel RamĆ³n; Villamor, Eduardo; PĆ©rez VizcaĆno, Francisco; Cogolludo Torralba, Ćngel LuisAims: A variety of vessels, such as resistance pulmonary arteries (PA) and fetoplacental arteries and the ductus arteriosus (DA) are specialized in sensing and responding to changes in oxygen tension. Despite opposite stimuli, normoxic DA contraction and hypoxic fetoplacental and PA vasoconstriction share some mechanistic features. Activation of neutral sphingomyelinase (nSMase) and subsequent ceramide production has been involved in hypoxic pulmonary vasoconstriction (HPV). Herein we aimed to study the possible role of nSMase-derived ceramide as a common factor in the acute oxygen-sensing function of specialized vascular tissues. Results: The nSMase inhibitor GW4869 and an anticeramide antibody reduced the hypoxic vasoconstriction in chicken PA and chorioallantoic arteries (CA) and the normoxic contraction of chicken DA. Incubation with interference RNA targeted to SMPD3 also inhibited HPV. Moreover, ceramide and reactive oxygen species production were increased by hypoxia in PA and by normoxia in DA. Either bacterial sphingomyelinase or ceramide mimicked the contractile responses of hypoxia in PA and CA and those of normoxia in the DA. Furthermore, ceramide inhibited voltage-gated potassium currents present in smooth muscle cells from PA and DA. Finally, the role of nSMase in acute oxygen sensing was also observed in human PA and DA. Innovation: These data provide evidence for the proposal that nSMase-derived ceramide is a critical player in acute oxygen-sensing in specialized vascular tissues. Conclusion: Our results indicate that an increase in ceramide generation is involved in the vasoconstrictor responses induced by two opposite stimuli, such as hypoxia (in PA and CA) and normoxia (in DA).