Browsing by Author "Diaz Araya, Guillermo"
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- ItemDexmedetomidine 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, SergioPharmacological 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.
- ItemEffects 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
- ItemEnalapril 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, SergioThe 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.
- ItemLipopolysaccharide Activates Toll-Like Receptor 4 and Prevents Cardiac Fibroblast-to-Myofibroblast Differentiation(HUMANA PRESS INC, 2017) Bolivar, Samir; Santana, Roxana; Ayala, Pedro; Landaeta, Rodolfo; Boza, Pia; Humeres, Claudio; Vivar, Raul; Munoz, Claudia; Pardo, Viviana; Fernandez, Samuel; Anfossi, Renatto; Diaz Araya, GuillermoBacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-beta 1 (TGF-beta 1), increasing alpha-smooth muscle actin (alpha-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-beta 1 signaling was described; however, it has not been studied whether in CF and CMF the expression of alpha-SMA induced by TGF-beta 1 is antagonized by LPS and the mechanism involved. In adult rat CF and CMF, alpha-SMA, ERK1/2, Akt, NF-kappa beta, Smad3, and Smad7 protein levels were determined by western blot, TGF-beta isoforms by ELISA, and alpha-SMA stress fibers by immunocytochemistry. CF and CMF secrete the three TGF-beta isoforms, and the secretion levels of TGF-beta 2 was affected by LPS treatment. In CF, LPS treatment decreased the protein levels of alpha-SMA, and this effect was prevented by TAK-242 (TLR4 inhibitor) and LY294002 (Akt inhibitor), but not by BAY 11-7082 (NF-kappa beta inhibitor) and PD98059 (ERK1/2 inhibitor). TGF-beta 1 increased alpha-SMA protein levels in CF, and LPS prevented partially this effect. In addition, in CMF alpha-SMA protein levels were decreased by LPS treatment, which was abolished by TAK-242. Finally, in CF LPS decreased the p-Smad3 phosphorylation and increased the Smad7 protein levels. LPS treatment prevents the CF-to-CMF differentiation and reverses the CMF phenotype induced by TGF-beta 1, through decreasing p-Smad3 and increasing Smad7 protein levels.