Browsing by Author "Vecchiola, Andrea"
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- ItemA Deletion Encompassing Exon 2 of the ALS Gene: Analysis of a Patient with ALS Deficiency and His Family(KARGER, 2018) Poggi, Helena; Arancibia, Monica; Benavides, Felipe; Lagos, Carlos; Vecchiola, Andrea; Dominguez Menendez, Gonzalo; Martinez Aguayo, Alejandro
- ItemCitosine-Adenine-Repeat Microsatellite of 11 beta-hydroxysteroid dehydrogenase 2 Gene in Hypertensive Children(OXFORD UNIV PRESS, 2016) Valdivia, Carolina; Carvajal, Cristian A.; Campino, Carmen; Allende, Fidel; Martinez Aguayo, Alejandro; Baudrand, Rene; Vecchiola, Andrea; Lagos, Carlos F.; Tapia Castillo, Alejandra; Fuentes, Cristobal A.; Aglony, Marlene; Solari, Sandra; Kalergis, Alexis M.; Garcia, Hernan; Owen, Gareth I.; Fardella, Carlos E.BACKGROUND
- ItemClassic and nonclassic apparent mineralocorticoid excess syndrome(Endocrine Society, 2020) Carvajal, Cristián A.; Tapia-Castillo, Alejandra; Vecchiola, Andrea; Baudrand, Rene; Fardella, Carlos© 2020 Endocrine Society. All rights reserved.Context: Arterial hypertension (AHT) is one of the most frequent pathologies in the general population. Subtypes of essential hypertension characterized by low renin levels allowed the identification of 2 different clinical entities: aldosterone-mediated mineralocorticoid receptor (MR) activation and cortisol-mediated MR activation. Evidence Acquisition: This review is based upon a search of Pubmed and Google Scholar databases, up to August 2019, for all publications relating to endocrine hypertension, apparent mineralocorticoid excess (AME) and cortisol (F) to cortisone (E) metabolism. Evidence Synthesis: The spectrum of cortisol-mediated MR activation includes the classic AME syndrome to milder (nonclassic) forms of AME, the latter with a much higher prevalence (7.1%) than classic AME but different phenotype and genotype. Nonclassic AME (NC-AME) is mainly related to partial 11βHSD2 deficiency associated with genetic variations and epigenetic modifications (first hit) and potential additive actions of endogenous or exogenous inhibitors (ie, glycyrrhetinic acid-like factors [GALFS]) and other factors (ie, age, high sodium intake) (second hit). Subjects with NC-AME are characterized by a high F/E ratio, low E levels, normal to elevated blood pressure, low plasma renin and increased urinary potassium excretion. NCAME condition should benefit from low-sodium and potassium diet recommendations and monotherapy with MR antagonists. Conclusion: NC-AME has a higher prevalence and a milder phenotypical spectrum than AME. NC-AME etiology is associated to a first hit (gene and epigene level) and an additive second hit. NC-AME subjects are candidates to be treated with MR antagonists aimed to improve blood pressure, end-organ damage, and modulate the renin levels.
- ItemD-Glucose stimulation of L-arginine transport and nitric oxicle synthesis results from activation of mitogen-activated protein kinases p42/44 and smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium(WILEY, 2007) Vasquez, Rodrigo; Farias, Marcelo; Vega, Jost Luis; Martin, Rody San; Vecchiola, Andrea; Casanello, Paola; Sobrevia, LuisElevated extracellular D-glucose increases transforming growth factor P I (TGF-P 1) release from human umbilical vein endothelium (HUVEC). TGF-P 1, via TGF-P receptors I (T beta RI) and T beta RII, activates Smad2 and mitogen -activated protein kinases p44 and p42 (p42/44 (mapk)). We studied whether D-glucose-stimulation Of L-arginine transport and nitric oxide synthesis involves TGF-beta 1 in primary cultures of HUVEC. TGF-P I release was higher (similar to 1.6-fold) in 25 mM (high) compared with 5 mM (normal) D-glucose. TGF-P I increases L-arginine transport (half maximal effect similar to 1.6 ng/ml) in normal D-glucose, but did not alter high D-glucose-increased L-arginine transport. TGF-P I and high D-glucose increased hCAT- I mRNA expression (similar to 8-fold) and maximal transport velocity (V-max), L- [(3) H]citrulline formation from L- [3 H]arginine (index of NO synthesis) and endothelial NO synthase (eNOS) protein abundance, but did not alter eNOS phosphorylation. TGF-beta 1 I and high D-gludose increased p42/44 mapk and Smad2 phosphorylation, an effect blocked by PD-98059 (MEK 1 /2 inhibitor). However, TGF-P I and high D-glucose were ineffective in cells expressing a truncated, negative dominant T beta RII High D-glucose increases L-arginine transport and eNOS expression following T beta RII activation by TGF-P I involving p42/44 (mapk) and Smad2 in HUVEC. Thus, TGF-P I could play a crucial role under conditions of hyperglycemia, such as gestational diabetes mellitus, which is
- ItemDepressive symptoms are associated with higher morning plasma cortisol in primary care subjects(2018) Capponi, Valentina; Carrasco, Carmen; Macchiavello, Stefano; Undurraga, Juan; Campino Johnson, María del Carmen; Carvajal, Cristian; Gomez, Teresita; Weiss, Cristian; Aedo Campos, Igor Iván; Vecchiola Cárdenas, Andrea Paola; Allende, Fidel; Solari, Sandra; Fardella B., Carlos; Baudrand Biggs, René; Capponi, Valentina; Carrasco, Carmen; Macchiavello, Stefano; Undurraga, Juan; Campino Johnson, María del Carmen; Carvajal, Cristian; Gomez, Teresita; Weiss, Cristian; Aedo Campos, Igor Iván; Vecchiola, Andrea; Allende, Fidel; Solari, Sandra; Fardella B., Carlos; Baudrand Biggs, René
- ItemDifferences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development(AMER PHYSIOLOGICAL SOC, 2011) Vecchiola, Andrea; Francisco de la Llera, Juan; Ramirez, Rodrigo; Olmos, Pablo; Herrera, Cristobal I.; Borzone, GisellaVecchiola A, de la Llera JF, Ramirez R, Olmos P, Herrera CI, Borzone G. Differences in acute lung response to elastase instillation in two rodent species may determine differences in severity of emphysema development. Am J Physiol Regul Integr Comp Physiol 301: R148-R158, 2011. First published April 13, 2011; doi:10.1152/ajpregu.00133.2011.-Elastase intratracheal instillation induces early emphysema in rodents. However, Syrian Golden hamsters develop more severe emphysema than Sprague-Dawley rats. We have reported species differences in oxidant/antioxidant balance modulating antiprotease function early after instillation. We now hypothesize that other components of the initial lung response to elastase might also be species-dependent. Sprague-Dawley rats and Syrian Golden hamsters received a single dose of pancreatic elastase (0.55 U/100 g body wt) to study acute lung injury biomarkers. Using serum, lung, and bronchoalveolar lavage fluid (BALF) samples, we evaluated changes in alveolar-capillary permeability, alpha 1-antitrypsin (alpha(1)-AT) concentration and activity, glutathione content, and proinflammatory cytokines. Rats showed a large increase in alveolar-capillary permeability and few hemorrhagic changes, whereas hamsters exhibited large hemorrhagic changes (P < 0.01) and mild transendothelial passage of proteins. Western blots showed a 30-fold increase in BALF alpha(1)-AT concentration in rats and only a 7-fold increase in hamsters (P < 0.001), with [alpha(1)-AT-elastase] complexes only in rats, suggesting differences in antiprotease function. This was confirmed by the alpha(1)-AT bioassay showing 20-fold increase in alpha(1)-AT activity in rats and only twofold increase in hamsters (P < 0.001). In rats, results were preceded by a 3-, 60-, and 20-fold increase in IL-6, IL-1 beta, and TNF-alpha respectively (P < 0.001). In hamsters, only IL-1 beta and TNF-alpha showed mild increases. All parameters studied were back to baseline by 4 days. In conclusion, several components of the initial lung response showed species differences. Cytokine release pattern and functional inhibition of alpha(1)-AT were the most significant components differing among species and could account for differences in susceptibility to elastase.
- ItemDifferences in lung glutathione metabolism may account for rodent susceptibility in elastase-induced emphysema development(AMER PHYSIOLOGICAL SOC, 2009) Borzone, Gisella R.; Liberona, Leonel F.; Bustamante, Andrea P.; Saez, Claudia G.; Olmos, Pablo R.; Vecchiola, Andrea; Villagran, Andrea; Serrano, Carolina; Reyes, Tatiana P.Borzone GR, Liberona LF, Bustamante AP, Saez CG, Olmos PR, Vecchiola A, Villagran A, Serrano C, Reyes TP. Differences in lung glutathione metabolism may account for rodent susceptibility in elastase-induced emphysema development. Am J Physiol Regul Integr Comp Physiol 296: R1113-R1123, 2009. First published January 14, 2009; doi: 10.1152/ajpregu.90361.2008.-Syrian Golden hamsters develop more severe emphysema than Sprague-Dawley rats after intratracheal instillation of the same dose of elastase/body weight. Although species variations in antielastase defenses may largely explain these results, other variables, such as differences in lung antioxidants, cannot be overlooked since oxidative stress modulates antiprotease activity. We propose that elastase instillation might affect lung glutathione (GSH) metabolism differently in these species. Our aim was to study in hamsters and rats, lung glutathione metabolism at different times, from the stage of diffuse alveolar damage to advanced emphysema. We measured total and oxidized glutathione content as well as activity and expression of enzymes related to GSH synthesis and redox cycling: gamma-glutamylcysteine synthetase, glutathione peroxidase, and glutathione reductase. Whereas rats showed no significant changes in these measurements, hamsters showed significant derangement in GSH metabolism early after elastase instillation: 25% fall in total GSH (P < 0.05) with no increase in oxidized glutathione associated with reduced enzyme activities 24 h after elastase [60% for gamma-glutamylcysteine synthetase (P < 0.01), 30% for glutathione peroxidase (P < 0.01), and 75% for glutathione reductase (P < 0.001)]. GSH homeostasis was restored at the end of the first week, involving transient increased expression of these enzymes. We conclude that elastase induces significant alterations in GSH metabolism of hamster lungs and no overall change in rat lungs. Although differences in disease severity may account for our findings, the hamster becomes vulnerable to functional inhibition of alpha(1)-antitrypsin by oxidants and thus, even more susceptible to injury than it would be, considering only its low alpha(1)-antitrypsin level.
- ItemHigh D-Glucose reduces SLC29A1 promoter activity and adenosine transport involving specific protein 1 in human umbilical vein endothelium(WILEY, 2008) Puebla, Carlos; Farias, Marcelo; Gonzalez, Marcelo; Vecchiola, Andrea; Aguayo, Claudio; Krause, Bernardo; Pastor Anglada, Marcal; Casanello, Paola; Sobrevia, LuisHigh D-glucose reduces human equilibrative nucleoside transporter 1 (hENT1)-mediated adenosine uptake involving endothelial nitric oxide synthase (eNOS), mitogen-activated protein (MAP) kinase kinases 1 and 2/MAP kinases p42/44 (MEK/ERKs), and protein kinase C (PKC) activation in human umbilical vein endothelium (HUVEC). Since NO represses SLC29A1 gene (hENT1) promoter activity we studied whether D-glucose-reduced hENT1-adenosine transport results from lower SLC29A1 expression in HUVEC primary cultures. HUVEC incubation (24 h) with high D-glucose (25 mM) reduced hENT1-adenosine transport and pGL3-hENT1(-1114) construct SLC29A1 reporter activity compared with normal D-glucose (5 mM). High D-glucose also reduced pGL3-hENT1(-1114) reporter activity compared with cells transfected with pGL3-hENT1(-795) Construct. N-G-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor), PD-98059 (MEK1/2 inhibitor), and/or calphostin C (PKC inhibitor) blocked D-glucose effects. Insulin(1 nM) and phorbol 12-myristate 13-acetate (PMA, 100 nM, PKC activator), but not 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD, 100 nM, PMA less active analogue) reduced hENT1-adenosine transport. L-NAME and PD-98059 blocked insulin effects. L-NAME, PD-98059, and calphostin C increased hENT1 expression without altering protein or mRNA stability. High D-glucose increased Sp1 transcription factor protein abundance and binding to SLC29A1 promoter, phenomena blocked by L-NAME, PD-98059, and calphostin C. Sp1 overexpression reduced SLC29A1 promoter activity in normal D-glucose, an effect reversed by L-NAME and further reduced by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor) in high D-glucose. Thus, reduced hENT1 -mediated adenosine transport in high D-glucose may result from increased Sp1 binding to SLC29A1 promoter down-regulating hENT1 expression. This phenomenon depends on eNOS, MEK/ERKs, and PKC activity, suggesting potential roles for these molecules in hyperglycemia-associated endothelial dysfunction.
- ItemInsulin restores glucose inhibition of adenosine transport by increasing the expression and activity of the equilibrative nucleoside transporter 2 in human umbilical vein endothelium(WILEY, 2006) Munoz, Gonzalo; San Martin, Rody; Farias, Marcelo; Cea, Luis; Vecchiola, Andrea; Casanello, Paola; Sobrevia, LuisL-Arginine transport and nitric oxide (NO) synthesis (L-arginine/NO pathway) are stimulated by insulin, adenosine or elevated extracellular D-glucose in human umbilical vein endothelial cells (HUVEC). Adenosine uptake via the human equilibrative nucleoside transporters 1 (hENT1) and 2 (hENT2) has been proposed as a mechanism regulating adenosine plasma concentration, and therefore its vascular effects in human umbilical veins. Thus, altered expression and/or activity of hENT1 or hENT2 could lead to abnormal physiological plasma adenosine level. We have characterized insulin effect on adenosine transport in HUVEC cultured in normal (5 mM) or high (25, mM) D-glucose. Insulin (1 nM) increased overall adenosine transport associated with higher hENT2-, but lower hENT1-mediated transport in normal D-glucose. insulin increased hENT2 protein abundance in normal or high D-glucose, but reduced hENT1 protein abundance in normal D-glucose. Insulin did not alter the reduced hENT1 protein abundance, but blocked the reduced hENT1 and hENT2 mRNA expression induced by high D-glucose. Insulin effect on hENT1 mRNA expression in normal D-glucose was blocked by N-G-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and mimicked by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor). L-NAME did not block insulin effect on hENT2 expression. In conclusion, insulin stimulation of overall adenosine transport results from increased hENT2 expression and activity via a NO-independent mechanism. These findings could be important in hyperglycemia-associated pathological pregnancies, such as gestational diabetes, where plasma adenosine removal by the endothelium is reduced, a condition that could alter the blood flow from the placenta to the fetus affecting fetus growth and development. J. Cell. Physiol. 209: 826-835, 2006. (c) 2006 Wiley-Liss, Inc.
- ItemPolymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population(OXFORD UNIV PRESS, 2014) Tapia Castillo, Alejandra; Carvajal, Cristian A.; Campino, Carmen; Vecchiola, Andrea; Allende, Fidel; Solari, Sandra; Garcia, Lorena; Lavanderos, Sergio; Valdivia, Carolina; Fuentes, Cristobal; Lagos, Carlos F.; Martinez Aguayo, Alejandro; Baudrand, Rene; Aglony, Marlene; Garcia, Hernan; Fardella, Carlos E.The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, G > A) and rs836478 (intron 3, T > C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort.
- ItemRole of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.(2016) Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage.