Browsing by Author "Lavandero, Sergio"

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    Ácido úrico: una molécula con acciones paradójicas en la insuficiencia cardiaca
    (2011) Alcaíno, Hernán; Greig, Douglas; Castro Gálvez, Pablo Federico; Verdejo Pinochet, Hugo; Mellado Suazo, Rosemarie; García, Lorena; Díaz Araya, Guillermo; Quiroga Lagos, Clara Rosa; Chiong, Mario; Lavandero, Sergio
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    Acute effect of iloprost inhalation on right atrial function and ventricular dyssynchrony in patients with pulmonary artery hypertension
    (2017) Gabrielli, Luigi; Ocaranza, María Paz; Sitges, Marta; Kanacri, Andrés; Saavedra Madariaga, Rodrigo Alejandro; Sepúlveda, Pablo; Sepúlveda, Luis; Rossel, Víctor; Zagolin, Mónica; Verdejo Pinochet, Hugo; Baraona Reyes, Fernando Exequiel; Zalaquett Sepúlveda, Ricardo; Chiong, Mario; Lavandero, Sergio; Castro Gálvez, Pablo Federico
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    Angiotensin I-converting enzyme gene polymorphism influences chronic hypertensive response in the rat Goldblatt model
    (LIPPINCOTT WILLIAMS & WILKINS, 2002) Ocaranza Jeraldino, María Paz; Piddo, Ana M.; Faundez, Perla; Lavandero, Sergio; Jalil Milad, Jorge Emilio
    Background and objective In humans, the insertion/ deletion polymorphism in the anglotensin (Ang) I converting enzyme (ACE) gene significantly determines ACE activity. The deletion allele induces higher ACE levels and is associated with hypertension in men. In the rat, a microsatellite marker in the ACE gene allows differentiation of the ACE alleles among strains with different ACE levels. We evaluated the effect of genetically determined ACE expression on the development of renovascular hypertension in the rat.
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    Angiotensin I-converting enzyme gene polymorphism influences chronic hypertensive response in the rat Goldblatt model
    (LIPPINCOTT WILLIAMS & WILKINS, 2002) Ocaranza Jeraldino, María Paz; Piddo, Ana M.; Faundez, Perla; Lavandero, Sergio; Jalil Milad, Jorge Emilio
    Background and objective In humans, the insertion/ deletion polymorphism in the anglotensin (Ang) I converting enzyme (ACE) gene significantly determines ACE activity. The deletion allele induces higher ACE levels and is associated with hypertension in men. In the rat, a microsatellite marker in the ACE gene allows differentiation of the ACE alleles among strains with different ACE levels. We evaluated the effect of genetically determined ACE expression on the development of renovascular hypertension in the rat.
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    Angiotensin I-converting enzyme insertion/deletion polymorphism and adrenergic response to exercise in hypertensive patients.
    (2002) Braun Jones, Vivian Sandra; Chamorro Spikin, Gastón Alberto; Cordova Alvestegui, Samuel Edmundo; Fardella Bello, Carlos Enrique; Jalil Milad, Jorge Emilio; Lavandero, Sergio; Ocaranza Jeraldino, María Paz; Schumacher, Erwin
    BackgroundThe insertion/deletion ACE polymorphism (ACE I/D) regulates different levels of circulating and tissue ACE activities, which may induce diverse adrenergic responses to physiological stimuli. The aim of this study was to evaluate the influence of
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    Angiotensin II-Regulated Autophagy Is Required for Vascular Smooth Muscle Cell Hypertrophy
    (2019) Mondaca-Ruff, David; Riquelme, Jaime A.; Quiroga Lagos, Clara Rosa; Norambuena-Soto, Ignacio; Sanhueza-Olivares, Fernanda; Villar-Fincheira, Paulina; Hernández-Díaz,Tomás; Cancino-Arenas, Nicole; San Martín, Alejandra; García, Lorena; Lavandero, Sergio; Chiong, Mario
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    Angiotensin-(1-9) reduces cardiovascular and renal inflammation in experimental renin-independent hypertension
    (2018) Gonzalez, Leticia; Novoa, Ulises; Moya, Jackeline; Gabrielli, Luigi; Jalil Milad, Jorge; Garcia, Lorena; Chiong, Mario; Lavandero, Sergio; Paz Ocaranza, Maria
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    Angiotensin-(1-9) regulates cardiac hypertrophy in vivo and in vitro
    (LIPPINCOTT WILLIAMS & WILKINS, 2010) Paz Ocaranza, Maria; Lavandero, Sergio; Jalil, Jorge E.; Moya, Jaqueline; Pinto, Melissa; Novoa, Ulises; Apablaza, Felipe; Gonzalez, Leticia; Hernandez, Carol; Varas, Manuel; Lopez, Rene; Godoy, Ivan; Verdejo, Hugo; Chiong, Mario
    Background Angiotensin-(1-9) is present in human and rat plasma and its circulating levels increased early after myocardial infarction or in animals treated with angiotensin-converting enzyme inhibitor. However, the cardiovascular effects of this peptide are unknown.
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    AT2 Receptor Mediated Activation of the Tyrosine Phosphatase PTP1B Blocks Caveolin-1 Enhanced Migration, Invasion and Metastasis of Cancer Cells
    (2019) Martínez-Meza, Samuel; Díaz, Jorge; Sandoval-Bórquez, Alejandra; Valenzuela-Valderrama, Manuel; Díaz-Valdivia, Natalia; Rojas-Celis, Victoria; Contreras, Pamela; Huilcaman, Ricardo; Ocaranza Jeraldino, María Paz; Chiong, Mario; Leyton, Lissette; Lavandero, Sergio; Quest, Andrew F. G.
    The renin-angiotensin receptor AT2R controls systemic blood pressure and is also suggested to modulate metastasis of cancer cells. However, in the latter case, the mechanisms involved downstream of AT2R remain to be defined. We recently described a novel Caveolin-1(CAV1)/Ras-related protein 5A (Rab5)/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling axis that promotes metastasis in melanoma, colon, and breast cancer cells. Here, we evaluated whether the anti-metastatic effect of AT2R is connected to inhibition of this pathway. We found that murine melanoma B16F10 cells expressed AT2R, while MDA-MB-231 human breast cancer cells did not. AT2R activation blocked migration, transendothelial migration, and metastasis of B16F10(cav-1) cells, and this effect was lost when AT2R was silenced. Additionally, AT2R activation reduced transendothelial migration of A375 human melanoma cells expressing CAV1. The relevance of AT2R was further underscored by showing that overexpression of the AT2R in MDA-MB-231 cells decreased migration. Moreover, AT2R activation increased non-receptor protein tyrosine phosphatase 1B (PTP1B) activity, decreased phosphorylation of CAV1 on tyrosine-14 as well as Rab5/Rac1 activity, and reduced lung metastasis of B16F10(cav-1) cells in C57BL/6 mice. Thus, AT2R activation reduces migration, invasion, and metastasis of cancer cells by PTP1B-mediated CAV1 dephosphorylation and inhibition of the CAV1/Rab5/Rac-1 pathway. In doing so, these observations open up interesting, novel therapeutic opportunities to treat metastatic cancer disease.
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    beta-Hydroxybutyrate Increases Exercise Capacity Associated with Changes in Mitochondrial Function in Skeletal Muscle
    (MDPI, 2020) Monsalves Alvarez, Matias; Morales, Pablo Esteban; Castro Sepulveda, Mauricio; Sepulveda, Carlos; Rodriguez, Juan Manuel; Chiong, Mario; Eisner, Veronica; Lavandero, Sergio; Troncoso, Rodrigo
    beta-hydroxybutyrate is the main ketone body generated by the liver under starvation. Under these conditions, it can sustain ATP levels by its oxidation in mitochondria. As mitochondria can modify its shape and function under different nutritional challenges, we study the chronic effects of beta-hydroxybutyrate supplementation on mitochondrial morphology and function, and its relation to exercise capacity. Male C57BL/6 mice were supplemented with beta-hydroxybutyrate mineral salt (3.2%) or control (CT, NaCl/KCl) for six weeks and submitted to a weekly exercise performance test. We found an increase in distance, maximal speed, and time to exhaustion at two weeks of supplementation. Fatty acid metabolism and OXPHOS subunit proteins declined at two weeks in soleus but not in tibialis anterior muscles. Oxygen consumption rate on permeabilized fibers indicated a decrease in the presence of pyruvate in the short-term treatment. Both the tibialis anterior and soleus showed decreased levels of Mitofusin 2, while electron microscopy assessment revealed a significant reduction in mitochondrial cristae shape in the tibialis anterior, while a reduction in the mitochondrial number was observed only in soleus. These results suggest that short, but not long-term, beta-hydroxybutyrate supplementation increases exercise capacity, associated with modifications in mitochondrial morphology and function in mouse skeletal muscle.
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    Circulating Vascular Cell Adhesion Molecule-1 (sVCAM-1) Is Associated With Left Atrial Remodeling in Long-Distance Runners
    (FRONTIERS MEDIA SA, 2021) Contreras Briceño, Felipe; Herrera, Sebastián; Vega Adauy, Julián; Salinas, Manuel; Ocaranza Jeraldino, María Paz; Jalil Milad, Jorge; Mandiola Ovalle, Jorge; García, Lorena; Chiong, Mario; Castro Galvez, Pablo Federico; Lavandero, Sergio; Gabrielli Nervi, Luigi Arnaldo
    Introduction: An increased risk of atrial fibrillation (AF) has been demonstrated in high-performance athletes. Soluble vascular adhesion molecule-1 (sVCAM-1), a biomarker involved in inflammation and cardiac remodeling, is associated with the development of AF in the general population. However, the relationship between sVCAM-1 and left atrial (LA) remodeling has been poorly investigated in long-distance runners (LDR).Aim: To determine the association between LA remodeling and sVCAM-1 levels in LDR during the training period before a marathon race.Methods: Thirty-six healthy male LDR (37.0 +/- 5.3 years; 174.0 +/- 7.0 height; BMI: 23.8 +/- 2.8; V degrees O-2-peak: 56.5 +/- 7.3 mL center dot kg(-1)center dot min(-1)) were evaluated in this single-blind and cross-sectional study. The LDR were separated into two groups according to previous training levels: high-training (HT) (n = 18) >= 100 km center dot week(-1) and low-training (LT) (n = 18) >= 70 and <100 km center dot week(-1). Also, 18 healthy non-active subjects were included as a control group (CTR). In all participants, transthoracic echocardiography was performed. sVCAM-1 blood levels were measured baseline and immediately finished the marathon race in LDR.Results: HT showed increased basal levels of sVCAM-1 (651 +/- 350 vs. 440 +/- 98 ng center dot mL(-1) CTR, p = 0.002; and vs. 533 +/- 133 ng center dot mL(-1) LT; p = 0.003) and a post-marathon increase (Delta sVCAM-1) (651 +/- 350 to 905 +/- 373 ng center dot mL(-1); p = 0.002), that did not occur in LT (533 +/- 133 to 651 +/- 138 ng center dot mL(-1); p = 0.117). In LDR was a moderate correlation between LA volume and sVCAM-1 level (rho = 0.510; p = 0.001).Conclusions: In male long-distance runners, sVCAM-1 levels are directly associated with LA remodeling. Also, the training level is associated with basal sVCAM-1 levels and changes after an intense and prolonged exercise (42.2 km). Whether sVCAM-1 levels predict the risk of AF in runners remains to be established.
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    Counter-regulatory renin–angiotensin system in cardiovascular disease
    (2019) Ocaranza, María Paz; Riquelme, Jaime A.; García, Lorena; Jalil Milad, Jorge; Chiong, Mario; Santos, Robson A. S.; Lavandero, Sergio
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    Dexmedetomidine preconditioning activates pro-survival kinases and attenuates regional ischemia/reperfusion injury in rat heart
    (ELSEVIER, 2012) Ibacache, Mauricio; Sanchez, Gina; Pedrozo, Zully; Galvez, Felipe; Humeres, Claudio; Echevarria, Ghislaine; Duaso, Juan; Hassi, Mario; Garcia, Lorena; Diaz Araya, Guillermo; Lavandero, Sergio
    Pharmacological preconditioning limits myocardial infarct size after ischemia/reperfusion. Dexmedetomidine is an alpha(2)-adrenergic receptor agonist used in anesthesia that may have cardioprotective properties against ischemia/reperfusion injury. We investigate whether dexmedetomidine administration activates cardiac survival kinases and induces cardioprotection against regional ischemia/reperfusion injury. In in vivo and ex vivo models, rat hearts were subjected to 30 min of regional ischemia followed by 120 min of reperfusion with dexmedetomidine before ischemia. The alpha(2)-adrenergic receptor antagonist yohimbine was also given before ischemia, alone or with dexmedetomidine. Erk1/2, Akt and eNOS phosphorylations were determined before ischemia/reperfusion. Cardioprotection after regional ischemia/reperfusion was assessed from infarct size measurement and ventricular function recovery. Localization of alpha(2)-adrenergic receptors in cardiac tissue was also assessed. Dexmedetomidine preconditioning increased levels of phosphorylated Erk1/2, Akt and eNOS forms before ischemia/reperfusion; being significantly reversed by yohimbine in both models. Dexmedetomidine preconditioning (in vivo model) and pen-insult protection (ex vivo model) significantly reduced myocardial infarction size, improved functional recovery and yohimbine abolished dexmedetomidine-induced cardioprotection in both models. The phosphatidylinositol 3-kinase inhibitor LY-294002 reversed myocardial infarction size reduction induced by dexmedetomidine preconditioning. The three isotypes of alpha(2)-adrenergic receptors were detected in the whole cardiac tissue whereas only the subtypes 2A and 2C were observed in isolated rat adult cardiomyocytes. These results show that dexmedetomidine preconditioning and dexmedetomidine pen-insult administration produce cardioprotection against regional ischemia/reperfusion injury, which is mediated by the activation of pro-survival kinases after cardiac alpha(2)-adrenergic receptor stimulation. (C) 2011 Elsevier B.V. All rights reserved.
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    Dissociating angiotensin 1-9 anticardiovascular remodeling effects from those on blood pressure
    (2014) Ocaranza, María Paz; Michea, Luis; Chiong, Mariod; Lavandero, Sergio; Jalil Milad, Jorge
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    Down syndrome critical region 1 gene, rcan1, helps maintain a more fused mitochondrial network
    (2018) Parra, Valentina; Altamirano, Francisco; Hernández Fuentes, Carolina P.; Tong, Dan; Kyrychenko, Victoriia; Rotter, David; Pedrozo, Zully; Hill, Joséph A.| Eisner Sagüés, Verónica Raquel; Lavandero, Sergio; Schneider, Jay W.; Rothermel, Beverly A.
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    Effects of atorvastatin therapy in heart failure: Oxidative stress, inflammation, endothelial dysfunction and exercise capacity
    (ELSEVIER SCIENCE INC, 2007) Miranda, Rodrigo; Castro, Pablo; Verdejo, Hugo; Greig, Douglas; Alcaino, Hernan; Bustos, Carlos; Vukasovic, Jose Luis; Godoy, Ivan; Diaz Araya, Guillermo; Lavandero, Sergio
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    Enalapril attenuates downregulation of angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat
    (LIPPINCOTT WILLIAMS & WILKINS, 2006) Ocaranza, Maria Paz; Godoy, Ivan; Jalil, Jorge E.; Varas, Manuel; Collantes, Patricia; Pinto, Melissa; Roman, Maritza; Ramirez, Cristian; Copaja, Miguel; Diaz Araya, Guillermo; Castro, Pablo; Lavandero, Sergio
    The early and long-term effects of coronary artery ligation on the plasma and left ventricular angiotensin-converting enzyme (ACE and ACE2) activities, ACE and ACE2 mRNA levels, circulating angiotensin (Ang) levels [Ang I, Ang-(1-7), Ang-(1-9), and Ang II], and cardiac function were evaluated 1 and 8 weeks after experimental myocardial infarction in adult Sprague Dawley rats. Sham-operated rats were used as controls. Coronary artery ligation caused myocardial infarction, hypertrophy, and dysfunction 8 weeks after surgery. At week 1, circulating Ang II and Ang-(1-9) levels as well as left ventricular and plasma ACE and ACE2 activities increased in myocardial-infarcted rats as compared with controls. At 8 weeks post-myocardial infarction, circulating ACE activity, ACE mRNA levels, and Ang II levels remained higher, but plasma and left ventricular ACE2 activities and mRNA levels and circulating levels of Ang-(1-9) were lower than in controls. No changes in plasma Ang-(1-7) levels were observed at any time. Enalapril prevented cardiac hypertrophy and dysfunction as well as the changes in left ventricular ACE, left ventricular and plasmatic ACE2, and circulating levels of Ang II and Ang-(1-9) after 8 weeks postinfafction. Thus, the decrease in ACE2 expression and activity and circulating Ang-(1-9) levels in late ventricular dysfunction post-myocardial infarction were prevented with enalapril. These findings suggest that in this second arm of the renin-angiotensin system, ACE2 may act through Ang-(1-9), rather than Ang-(1-7), as a counterregulator of the first arm, where ACE catalyzes the formation of Ang II.
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    Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagy
    (2012) Troncoso, Rodrigo; Vicencio, Jose Miguel; Parra, Valentina; Nemchenko, Andriy; Kawashima, Yuki; Del Campo, Andrea; Toro, Barbra; Battiprolu, Pavan K.; Aranguiz, Pablo; Chiong, Mario; Yakar, Shoshana; Gillette, Thomas G.; Hill, Joseph A.; Abel, Evan Dale; LeRoith, Derek; Lavandero, Sergio
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    Enfermedades cardiovasculares y cáncer: ¿dos entidades mutuamente relacionadas?
    (2019) Mendoza-Torres, Evelyn; Bravo-Sagua, Roberto; Villa, Mónica; Flores, Nancy; Olivares, María José; Calle, Ximena; Riquelme, Jaime A.; Bambs S., Claudia; Castro Gálvez, Pablo Federico; Lavandero, Sergio
    Las enfermedades cardiovasculares y el cáncer son enfermedades crónicas transmisibles culturalmente, y las dos causas principales de mortalidad en el mundo. Además del gran impacto sobre la mortalidad y morbilidad, estas enfermedades han mostrado un alto grado de relación entre ellas debido, entre otras razones, a que comparten factores de riesgo y mecanismos biológicos. La alta incidencia de enfermedad cardiovascular en pacientes con cáncer es un fenómeno conocido que ha orientado el desarrollo del campo interdisciplinario de la cardio-oncología. Sin embargo, en la última década han surgido evidencias que muestran el papel que desempeñan las enfermedades cardiovasculares en el desarrollo de cáncer. Un estudio reciente publicado por Meijers y cols, en agosto de 2018 en Circulation, mostró que la insuficiencia cardiaca post-infarto del miocardio contribuye significativamente al desarrollo del cáncer de colón, apoyando lo obtenido en estudios epidemiológicos anteriores. Este estudio también sugiere que el crecimiento tumoral podría producirse por factores secretados por el corazón insuficiente abriendo un amplio grupo de posibilidades de investigación en lo que sería un nuevo campo de la medicina cuyo propósito sería el desarrollo de nuevas estrategias para el seguimiento y tratamiento del cáncer en pacientes con enfermedades cardiovasculares. El presente artículo revisa los factores de riesgo, y mecanismos celulares y moleculares, que son comunes en las enfermedades cardiovasculares y el cáncer, la contribución del trabajo de Meijers y cols hacia un mayor entendimiento de la interrelación entre estas patologías y las perspectivas futuras con respecto a los nuevos hallazgos.
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    ER-to-mitochondria miscommunication and metabolic diseases
    (2015) López Crisosto, Camila; Bravo Sagua, Roberto; Rodriguez Peña, Marcelo; Mera, Claudia; Castro Gálvez, Pablo Federico; Quest, Andrew F. G.; Rothermel, Beverly A.; Cifuentes, Mariana; Lavandero, Sergio