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Activation of Peroxisome‐Proliferator‐activated receptors alpha and gamma mediates remote ischemic preconditioning against myocardial infarction
Author(s) -
Lotz Christopher,
Redel Andreas,
Stumpner Jan,
Thorsten Smul,
TischerZeitz Tobias,
Schmidt Johannes,
Wunder Christian,
Lange Markus,
Roewer Norbert,
Kehl Franz
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.763.1
Subject(s) - ischemic preconditioning , antagonist , peroxisome proliferator activated receptor , ischemia , myocardial infarction , receptor , chemistry , medicine , cardiology , pharmacology
Background Remote ischemic preconditioning (RIPC) protects the heart against myocardial infarction. We tested the hypothesis that remote ischemic preconditioning is mediated by PPARα and PPARγ activation. Methods New Zealand white rabbits (n = 78) were subjected to a 30‐min coronary artery occlusion and 3 h of reperfusion. 3 cycles of RIPC consisted of 10 minutes renal ischemia alternating with 10 minutes of reperfusion. In different groups animals received the PPARα‐Antagonist GW6471 or the PPARγ‐Antagonist GW9662 alone or in combination with RIPC. Infarct size (IS) was determined gravimetrically. Myocardial tissue levels of PGJ 2 and nitrite/nitrate (NO x ), as well as PPAR DNA binding activity were measured using specific assays. Data are mean±SD. Results RIPC significantly reduced myocardial infarct size (42.2±4.9%*, p<0.05), compared to control (61±1.9%), and increased PPAR DNA‐binding activity (189.6±19.8RLU*, p<0.05) and tissue levels of PGJ 2 (179.7±7.9 pg/ml*, p<0.05). Infarct size reduction and increased PPAR DNA‐binding activity by RIPC was abolished by GW6471 (56.8±4.7% and 61.1±14.2RLU) or GW9662 (57.4±3.3% and 52.7±16.9RLU), in the presence of significantly reduced tissue levels of NO x (5.4±0.3μM* and 4.3±0.2μM*, p<0.05). Conclusion The results obtained suggest a pathway whereby RIPC leads to the production of PGJ 2 , activating PPARα and PPARγ, in turn mediating the production of NO.