Browsing by Author "Carvajal Maldonado, Cristián Andrés"

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    Age-Related Changes in 11 beta-Hydroxysteroid Dehydrogenase Type 2 Activity in Normotensive Subjects
    (2013) Campino Johnson, María del Carmen; Martínez Aguayo, Alejandro Gregorio; Baudrand Biggs, René; Carvajal Maldonado, Cristián Andrés; Aglony Imbarack, Marlene Elizabeth; García Bruce, Hernán; Padilla Pérez, Oslando; Kalergis Parra, Alexis Mikes; Fardella B., Carlos
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    Aldosterona e IL-17 en la génesis de la hipertensión arterial mineralocorticoídea, un estudio ex vivo
    (2016) Vecchiola Cárdenas, Andrea Paola; Cristóbal Fuentes, Z.; Muñoz Durango, Natalia; Tapia Castillo, Alejandra; González Gómez, Luis M.; Baudrand Biggs, René; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Kalergis Parra, Alexis Mikes; Carlos, F.; Lagos, A.; Fardella B., Carlos; Vecchiola Cárdenas, Andrea Paola; Cristóbal Fuentes, Z.; Muñoz Durango, Natalia; Tapia Castillo, Alejandra; González Gómez, Luis M.; Baudrand Biggs, René; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Kalergis Parra, Alexis Mikes; Carlos, F.; Lagos, A.; Fardella B., Carlos
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    Aldosterone Production and Signaling Dysregulation in Obesity
    (2016) Vecchiola Cárdenas, Andrea Paola; Lagos, C.; Carvajal Maldonado, Cristián Andrés; Baudrand Biggs, René; Fardella B., Carlos
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    Clinical, Biochemical, and Genetic Characteristics of "Nonclassic" Apparent Mineralocorticoid Excess Syndrome
    (2019) Tapia Castillo, Alejandra; Baudrand Biggs, René; Vaidya, Anand; Campino Johnson, María del Carmen; Allende, Fidel; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Fardella B., Carlos; Solari, Sandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Valdivia, Carolina; Tapia Castillo, Alejandra; Baudrand Biggs, René; Vaidya, Anand; Campino Johnson, María del Carmen; Allende, Fidel; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Fardella B., Carlos; Solari, Sandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Valdivia, Carolina
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    Detection of a novel severe mutation affecting the CYP21A2 gene in a Chilean male with salt wasting congenital adrenal hyperplasia
    (2020) Arteaga U., Eugenio; Valenzuela Pino, Felipe Patricio; Lagos, C. F.; Lagos, M.; Martínez García, Alejandra Constanza; Baudrand Biggs, René; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos
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    Different effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro
    (2013) Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Allende, Fidel; Campino Johnson, María del Carmen; Valdivia, Carolina.; Tapia Castillo, Alejandra.; Owen, Gareth Ivor; Solari Gajardo, Sandra; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; Ogishima, Tadashi.; Mukai, Kuniaki.
    Abstract Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone action, which could be involved in protecting pregnant women with FH-1 against hypertension. In vitro, both enzymes showed comparable kinetic parameters, but ASWT was more strongly inhibited than ASCE. This study implicates a new role for progesterone in the regulation of aldosterone levels that could contribute, along with other factors, to the maintenance of an adequate aldosterone-progesterone balance in pregnancy.Abstract Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone action, which could be involved in protecting pregnant women with FH-1 against hypertension. In vitro, both enzymes showed comparable kinetic parameters, but ASWT was more strongly inhibited than ASCE. This study implicates a new role for progesterone in the regulation of aldosterone levels that could contribute, along with other factors, to the maintenance of an adequate aldosterone-progesterone balance in pregnancy.
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    Downregulation of exosomal miR-192-5p and miR-204-5p in subjects with nonclassic apparent mineralocorticoid excess.
    (2019) Tapia Castillo, Alejandra.; Barros, Eric.; Allende, Fidel; Vecchiola Cárdenas, Andrea Paola; Fardella B., Carlos; Carvajal Maldonado, Cristián Andrés; Guanzon, Dominic.; Palma, Carlos.; Lai, Andrew.; Salomón Gallo, Carlos Francisco.
    Abstract Background The “nonclassic” apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. Methods We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n = 10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500. Results We found that NC-AME subjects had lower cortisone (p < 0.0001), higher F/E ratio (p < 0.0001), lower serum potassium (p = 0.009) and higher FEK 24 h (p = 0.03) than controls. We found miR-204-5p (fold-change = 0.115; p 0.001) and miR-192-5p (fold-change = 0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r = 0.45; p 0.028) and miR-204-5p expression with SBP (r = − 0.48, p 0.027) and F/E ratio (r = − 0.48; p 0.026). Conclusions These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.
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    Epigenetics and arterial hypertension : the challenge of emerging evidence
    (2015) Friso, Simonetta; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; Olivieri, Oliviero
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    Esteatosis Hepática: ¿Preludio de diabetes tipo 2 en población pediátrica?
    (2014) Piazzarollo Loureiro, Carolina; Martínez Aguayo, Alejandro Gregorio; Campino Johnson, María del Carmen; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; García Bruce, Hernán
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    High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome
    (2014) Baudrand Biggs, René; Campino Johnson, María del Carmen; Carvajal Maldonado, Cristián Andrés; Olivieri, O.; Guidi, G.; Faccini, G.; Vöhringer, P.A.; Cerda, Jaime; Owen, Gareth Ivor; Kalergis Parra, Alexis Mikes; Fardella B., Carlos
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    Hiperaldoteronismo primario y otras formas de hipertension arterial endocrina
    (2016) Carvajal Maldonado, Cristián Andrés; Baudrand Biggs, René; Fardella B., Carlos
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    Hipertension arterial mineralocorticoidea
    (2013) Fardella B., Carlos; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Tapia Castillo, A.; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán
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    Hypertensive Patients That Respond to Aldosterone Antagonists May Have a Nonclassical 11β-HSD2 Deficiency.
    (2017) Tapia Castillo, Alejandra; Carvajal Maldonado, Cristián Andrés; Allende, Fidel; Campino Johnson, María del Carmen; Fardella B., Carlos
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    Increased levels of oxidative stress, subclinical inflammation, and myocardial fibrosis markers in primary aldosteronism patients
    (2010) Stehr, Carlos B.; Mellado Suazo, Rosemarie; Ocaranza, María Paz; Carvajal Maldonado, Cristián Andrés; Mosso Gómez, Lorena; Becerra, Elia; Solis, Margarita; Garcia, Lorena; Lavandero, Sergio; Jalil Milad, Jorge; Fardella B., Carlos
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    LC-MS/MS Method for the Simultaneous Determination of Free Urinary Steroids
    (2014) Allende, Fidel; Solari Gajardo, Sandra; Campino Johnson, María del Carmen; Carvajal Maldonado, Cristián Andrés; Lagos Arévalo, Carlos Fernando; Vecchiola Cárdenas, Andrea Paola; Baudrand Biggs, René; Owen, Gareth Ivor; Fardella B., Carlos
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    Progressive 11β-hydroxysteroid dehydrogenase type 2 insufficiency as kidney function declines
    (2024) Uslar N., Thomas; Newman, Andrew J.; Tapia Castillo, Alejandra; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; Allende, Fidel; Solari, Sandra; Tsai, Laura C.; Milks, Julia; Cherney, Michael; Stouffer, David G.; Auchus, Richard; Brown, Jenifer M.; Baudrand Biggs, René; Vaidya, Anand
    Background It has been postulated that chronic kidney disease (CKD) is a state of relative 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11 beta HSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range. Methods Adult participants were recruited at 2 academic centers. A discovery cohort (n = 500) enrolled individuals with estimated glomerular filtration rate (eGFR) ranging from normal to CKD stage 5, in whom serum cortisol-to-cortisone (F/E) was measured as a biomarker of 11 beta HSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR >= 60 mL/min/1.73 m(2)) in whom 11 beta HSD2 activity was assessed via serum F/E and 11-hydroxy-to-11-keto androgen (11OH/K) ratios following multiple maneuvers: oral sodium suppression test, dexamethasone suppression test (DST), and ACTH-stimulation test (ACTHstim). Results In the discovery cohort, lower eGFR was associated with higher F/E (P-trend < .001). Similarly, in the validation cohort, with normal eGFR, an inverse association between eGFR and both F/E and 11OH/K ratios was observed (P-trend < .01), which persisted following DST (P-trend < .001) and ACTHstim (P-trend < .05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F/E (P-trend < .01) and with lower eGFR (P-trend < .0001). Conclusion A continuum of declining 11 beta HSD2 activity was observed with progressively lower eGFR in individuals spanning a wide spectrum of kidney function, including those with apparently normal kidney function. These findings implicate cortisol-mediated MR activation in the pathophysiology of hypertension and cardiovascular disease in CKD.
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    Refractory depression in a patient with peripheral resistance to thyroid hormone (RTH) and the effect of triiodothyronine treatment
    (2007) Fardella B., Carlos; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Mosso Gómez, Lorena
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    Renal exosomes and their role in primary aldosteronism: an in vitro and in vivo approach
    (2020) Barros Lamus, Eric Raúl; Carvajal Maldonado, Cristián Andrés; Pontificia Universidad Católica de Chile. Escuela de Medicina
    Los exosomas renales son liberados por las células epiteliales que delimitan la nefrona, transportan información biológica. Aunque es conocido que los exosomas modulan la señalización purinérgica en tejidos extra-renales, se desconoce si exosomas renales realizan este tipo de regulación. La señalización purinérgica es crucial para la fisiología y el transporte renal de sodio, principalmente debido a sus efectos sobre el canal epitelial de sodio (ENaC). El aldosteronismo primario (HAP) es una patología caracterizada por elevados niveles de aldosterona y aumento en la actividad del ENaC, que podría modificar los exosomas renales. Hipótesis: exosomas renales regulan procesos celulares relacionados con el transporte de sodio mediante la modulación de la señalización purinérgica y la expresión de ENaC en el epitelio renal, y su concentración, bioactividad y cargo se modifica en el HAP. Objetivo: estudiar exosomas renales como nuevos reguladores de la señalización purinérgica y el transporte de sodio en células epiteliales renales, y los efectos de altos niveles de aldosterona en la concentración, bioactividad y cargo proteico de exosomas en pacientes con HAP y en un modelo celular de aldosteronismo. Métodos: se aislaron exosomas de células del túbulo proximal (HK-2), colector (HCD), muestras de orina humana (n=32) mediante ultracentrifugación. Se determinó el efecto de exosomas HK-2 y HCD sobre el ATP extracelular y sobre la expresión del canal epitelial de sodio (ENaC) y otros genes purinérgicos mediante luminiscencia y qPCR respectivamente. El efecto de aldosterona sobre la concentración de exosomas de células HK-2 y HCD se evaluó mediante Nanotracking Analysis (NTA). El proteoma, concentración y bioactividad de exo-u de pacientes HAP se evaluó utilizando espectrometría, NTA y luminiscencia, respectivamente. Resultados: Exosomas de HK-2 aumentan (40%) y exosomas de HCD disminuyen (50%) el ATP extracelular en células HCD, los últimos mediante hidrólisis del ATP. Exosomas HK-2 disminuyen (30%) y exosomas de HCD aumentan (30%) la expresión de ENaC en HCD. Aldosterona aumenta la concentración de exosomas en HK-2 (63%) y HCD (87%). Solo exosomas HCD apicales hidrolizan. U-exo de pacientes HAP son mas pequeños (8%) y abundantes (70%) comparados con controles. ORM1 en u-exo de pacientes HAP destaca como potencial biomarcadores de HAP, los cuales además aumentan la expresión de ENaC en células HCD. Conclusión: exosomas luminales regulan procesos asociados al transporte de sodio modulando la señalización purinérgica y la expresión de ENaC en una forma dependiente del segmento que origina los exosomas. Aldosterona esta involucrada en la liberación de exosomas. En el HAP se modifican los efectos de u-exo sobre ENaC. La abundancia de ORM1 en u-exo destaca como potencial biomarcador de HAP.
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    Serum cortisol and cortisone as potential biomarkers of partial 11β-hydroxysteroid dehydrogenase type 2 deficiency
    (2018) Carvajal Maldonado, Cristián Andrés; Tapia Castillo, Alejandra; Valdivia, Carolina P.; Allende, Fidel; Solari Gajardo, Sandra; Lagos Arévalo, Carlos Fernando; Campino Johnson, María del Carmen; Martínez Aguayo, Alejandro Gregorio; Vecchiola Cárdenas, Andrea Paola; Pinochet, Constanza
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    Sodium intake is associated with endothelial damage biomarkers and metabolic dysregulation
    (2018) Campino Johnson, María del Carmen; Baudrand Biggs, René; Valdivia, Carolina A.; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Tapia Castillo, Alejandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; García, Lorena; Allende, Fidel