Person: Olivencia Plaza, Miguel Ángel
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First Name
Miguel Ángel
Last Name
Olivencia Plaza
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Farmacología y Toxicología
Area
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6 results
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Item Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension(Journal of Clinical Medicine, 2020) Callejo Arranz, María; Mondejar Parreño, Gema; Esquivel Ruiz, Sergio Antonio; Olivencia Plaza, Miguel Ángel; Moreno Gutiérrez, Laura; Blanco, Isabel; Escribano Subías, María Pilar; Cogolludo Torralba, Ángel Luis; Barbera, Joan Albert; Pérez Vizcaíno, 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 Oxidized soluble guanylyl cyclase causes erectile dysfunction in alcoholic mice(British Journal of Pharmacology, 2023) Olivencia Plaza, Miguel Ángel; Gil De Biedma Elduayen, Leticia; Giménez Gómez, Pablo; Bianca Barreira; Argentina Fernández; Javier Angulo; Colado Megías, María Isabel; O'Shea Gaya, María Esther; Pérez Vizcaíno, FranciscoBackground and purposeAlcohol abuse has been associated with erectile dysfunction (ED), but the implicated molecular mechanisms are unresolved. This study analyses the role of alterations in soluble guanylyl cyclase (sGC) in ED.Experimental approachED was analysed in adult male C57BL/6J mice subjected to the Chronic Intermittent Ethanol (CIE) paradigm. Erectile function was assessed in anaesthetised mice in vivo by evaluating intracavernosal pressure (ICP) and in vitro in isolated mice corpora cavernosa (CC) mounted in a myograph. Protein expression and reactive oxygen species were analysed by western blot and dihydroethidium staining, respectively.Key resultsIn CIE mice, we observed a significant decrease in the relaxant response of the CC to stimulation of NO release from nitrergic nerves by electrical field stimulation, to NO release from endothelial cells by acetylcholine, to the PDE5 inhibitor sildenafil, and to the sGC stimulator riociguat. Conversely, the response to the sGC activator cinaciguat, whose action is independent of the oxidation state of sGC, was significantly enhanced in these CC. The responses to adenylyl cyclase stimulation with forskolin were unchanged. We found an increase in reactive oxygen species in the CC from CIE mice as well as an increase in CYP2E1 and NOX2 protein expression. In vivo pre‐treatment with tempol prevented alcohol‐induced erectile dysfunction.Conclusions and implicationsOur results demonstrate that alcoholic mice show ED in vitro and in vivo due to an alteration in the redox state of sGC and suggest that sGC activators may be effective in ED associated with alcoholism.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, María; Morales Cano, Daniel; Mondejar Parreño, Gema; Barreira, Bianca; Esquivel Ruiz, Sergio Antonio; Olivencia Plaza, Miguel Ángel; Moreno Gutiérrez, Laura; Cogolludo Torralba, Ángel Luis; Pérez Vizcaíno, 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 Vitamin D Receptor Deficiency Upregulates Pulmonary Artery Kv7 Channel Activity(International Journal of Molecular Sciences, 2023) Olivencia Plaza, Miguel Ángel; Villegas Esguevillas, Marta; Sancho González, María; Barreira, Bianca; Paternoster, Elena; Adão, Rui; Larriba, María Jesús; Cogolludo Torralba, Ángel Luis; Pérez Vizcaíno, FranciscoRecent evidence suggests that vitamin D is involved in the development of pulmonary arterial hypertension (PAH). The aim of this study was to analyze the electrophysiological and contractile properties of pulmonary arteries (PAs) in vitamin D receptor knockout mice (Vdr−/−). PAs were dissected and mounted in a wire myograph. Potassium membrane currents were recorded in freshly isolated PA smooth muscle cells (PASMCs) using the conventional whole-cell configuration of the patch-clamp technique. Potential vitamin D response elements (VDREs) in Kv7 channels coding genes were studied, and their protein expression was analyzed. Vdr−/− mice did not show a pulmonary hypertensive phenotype, as neither right ventricular hypertrophy nor endothelial dysfunction was apparent. However, resistance PA from these mice exhibited increased response to retigabine, a Kv7 activator, compared to controls and heterozygous mice. Furthermore, the current sensitive to XE991, a Kv7 inhibitor, was also higher in PASMCs from knockout mice. A possible VDRE was found in the gene coding for KCNE4, the regulatory subunit of Kv7.4. Accordingly, Vdr−/− mice showed an increased expression of KCNE4 in the lungs, with no changes in Kv7.1 and Kv7.4. These results indicate that the absence of Vdr in mice, as occurred with vitamin D deficient rats, is not sufficient to induce PAH. However, the contribution of Kv7 channel currents to the regulation of PA tone is increased in Vdr−/− mice, resembling animals and humans suffering from PAH.- Project number: 266
Item Gestión de exámenes online. Base de datos de preguntas y desarrollo de software(2021) Pérez Vizcaíno, Francisco; Esquivel Ruiz, Sergio Antonio; Gil De Biedma Elduayen, Leticia; Macías Montero, Miguel; Morales Puerto, Nuria; Núñez De La Calle, Carlos; Olivencia Plaza, Miguel Ángel; Bas Caro, Manuel; Caso Fernandez, Javier Rubén; Cogolludo Torralba, Ángel Luis; García Bueno, Borja; Gutiérrez Lopez, María Dolores; Hurtado Moreno, Olivia; Leza Cerro, Juan Carlos; Moreno Gutiérrez, Laura; O'Shea Gaya, María Esther; Pradillo Justo, Jesús Miguel; Vidal Casado, Rebeca - Project number: 238
Item Base de datos de preguntas y actualización del software. Herramientas para la generación de exámenes presenciales u online(2022) O'Shea Gaya, María Esther; Pérez Vizcaíno, Francisco; Caso Fernández, Javier Rubén; Cogolludo Torralba, Ángel Luis; García Bueno, Borja; Gutiérrez López, María Dolores; Hurtado Moreno, Olivia; Leza Cerro, Juan Carlos; Moreno Gutiérrez, Laura; Pradillo Justo, Jesús Miguel; Vidal Casado, Rebeca; Esquivel Ruiz, Sergio Antonio; Gil De Biedma Elduayen, Leticia; Macías Montero, Miguel; Morales Puerto, Nuria; Núñez De La Calle, Carlos; Olivencia Plaza, Miguel Ángel; Bas Caro, Manuel; Morales Cano, Daniel