title: Targeting the molecular mechanisms of ischemic damage: Protective effects of alpha-crystallin-B.
abstract: OBJECTIVE
  Molecular chaperones constitute protectors of intracellular protein integrity and seem to confer short-term defence against various cell insults. Myocardial damage is associated to a loss of protective chaperones. Ischemic post-conditioning (IPost-Co) is a procedure that seems to protect against reperfusion injury. However, little is known on alpha-crystallin-B-chain (cryab/HspB5) evolution in IPost-Co. Here we have investigated cryab in myocardial ischemia and IPost-Co.
  
  
  RESULTS
  Pigs underwent closed-chest 1.5h mid-left anterior descending (LAD) balloon occlusion and were either sacrificed without reperfusion (I;N=10), subjected to 2.5h of reperfusion and sacrificed (I/R; N=5); or subjected to IPost-Co before reperfusion and sacrificed 2.5h afterwards (IPost-Co; N=5). A sham-operated group was included (N=6). Proteomic analysis (2-D-electrophoresis/MALDI-TOF/TOF) revealed cryab as a single spot (20kDa; pI7.6). Myocardial cryab-20-protein and cryab-gene expression levels were decreased after ischemia and I/R(P<0.05). After IPost-Co, cryab-20-protein and cryab-gene expression levels were similar to those found in the heart of sham-operated animals (P<0.05). There was a direct correlation between LVEF-improvement after IPost-Co and myocardial cryab-20-protein levels. In a mice proof-of-principle study, cryab-20-peptide was synthesized and administered 1h before LAD-ligation and ECG-proven MI. A 59% reduction in infarct size was achieved in cryab-20-treated animals (P<0.05).
  
  
  CONCLUSIONS
  Ischemia and reperfusion induce a decrease in myocardial cryab-20-protein levels together with a clinical impairment of cardiac function. IPost-Co induces a clinical improvement of cardiac function and a preservation of cryab-20 levels. Intervention studies on a mice-MI model showed that cryab-20-peptide administration reduces infarct size. All together our results show a significant cardioprotective effect of cryab.
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Cubedo
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Vilahur
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Casaní
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Guiomar
authors.initials: G
authors.lastname: Mendieta
authors.affiliation: Department of Vascular Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Efrem
authors.initials: E
authors.lastname: Gómez-Jabalera
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Juan-Babot
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC) and Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain; Cardiovascular Research Chair UAB, Barcelona, Spain. Electronic address: lbadimon@csic-iccc.org.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011897:Random Allocation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013552:Swine; D038201:alpha-Crystallins / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D038201:alpha-Crystallins
keywords: Alpha-crystallin-B-chain; Cardioprotection; HspB5; Ischemic post-conditioning; Myocardial ischemia