title: Postconditioning protects against reperfusion injury in hypertensive dilated cardiomyopathy by activating MEK/ERK1/2 signaling.
abstract: BACKGROUND
  Postconditioning (PostC) cardioprotection has been related to up-regulation of survival kinases; however, the efficacy of PostC and the role of ERK1/2 (extracellular signal-regulated kinase 1/2) remain to be substantiated in hypertension states that may produce "pathologic remodeling." Therefore, in this work we compared PostC effect and assessed the role of ERK1/2 activation in a model of hypertensive dilated cardiomyopathy (DCM), versus normal (Sham) and compensated hypertrophy (CH) models.
  
  
  RESULTS
  Rats were subjected to angiotensin II administration until development of cardiovascular diseases. Then, isolated hearts underwent ischemia followed by PostC and reperfusion. PostC maintained the double product in all groups. PostC reduced infarct size from 36.16 ± 3% to 9.8% ± 2.2 in Sham, from 37.5 ± 2.4% to 12 ± 3% in CH, and from 40 ± 2.4% to 11.55 ± 3% in DCM. Inhibition of the mitogen-activated protein kinase kinase (MEK)/ERK1/2 pathway had different effects on PostC-conferred cardioprotection in the evaluated groups. Interestingly, although phosphatidylinositol-3-kinase activation was negligible in PostC DCM hearts, we observed Akt activation.
  
  
  CONCLUSIONS
  PostC confers cardioprotection through alternative survival pathways in normal and CH hearts, and cardiac function recovery in DCM relies mainly on MEK/ERK1/2 cascade. Down-regulation of phosphatidylinositide 3-kinase does not affect the cardioprotective response in DCM, because MEK/ERK1/2 cascade may convey direct Akt activation, strengthening downstream signaling.
authors: Department of Cardiovascular Medicine, Ignacio Chávez National Institute of Cardiology, México City, México.
authors: Sauri
authors: S
authors: Hernández-Reséndiz
authors: Francisco-Javier
authors: FJ
authors: Roldán
authors: Francisco
authors: F
authors: Correa
authors: Eduardo
authors: E
authors: Martínez-Abundis
authors: Gabriel
authors: G
authors: Osorio-Valencia
authors: Oscar
authors: O
authors: Ruíz-de-Jesús
authors: Erick
authors: E
authors: Alexánderson-Rosas
authors: Rosa M
authors: RM
authors: Vigueras
authors: Martha
authors: M
authors: Franco
authors: Cecilia
authors: C
authors: Zazueta
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000201:enzymology*; D057775:Ischemic Postconditioning / Q000379:methods*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020929:Mitogen-Activated Protein Kinase Kinases