HDL protects against ischemia reperfusion injury by preserving mitochondrial integrity

Autor: Sarah Pedretti, Richard W. James, Damian Hacking, Lydia Lacerda, Miguel Frias, Sarin Somers, Sandrine Lecour, Lionel H. Opie
Jazyk: angličtina
Rok vydání: 2013
Předmět:
STAT3 Transcription Factor
medicine.medical_specialty
Cell Survival
STAT3 Transcription Factor/genetics
Ischemia
Myocardial Infarction
Myocardial Reperfusion Injury
Pharmacology
Cholesterol
HDL/metabolism
Myocardial Infarction/metabolism/pathology
Myocytes
Cardiac/metabolism/pathology
chemistry.chemical_compound
Mice
Myocardial Reperfusion Injury/metabolism/pathology
Mitochondria/metabolism
medicine
Animals
Myocytes
Cardiac
cardiovascular diseases
Phosphorylation
STAT3
Cardioprotection
ddc:616
Cell Survival/physiology
Mice
Knockout
biology
Chemistry
Tumor Necrosis Factor-alpha
Signal Transduction/physiology
MPTP
Phosphorylation/physiology
Cholesterol
HDL
medicine.disease
Surgery
Mitochondria
Mitochondrial Membranes/metabolism
Mice
Inbred C57BL
Mitochondrial permeability transition pore
Mitochondrial Membranes
biology.protein
STAT protein
Tumor Necrosis Factor-alpha/genetics
Tumor necrosis factor alpha
Cardiology and Cardiovascular Medicine
Reperfusion injury
Signal Transduction
Zdroj: Atherosclerosis, Vol. 228, No 1 (2013) pp. 110-6
ISSN: 0021-9150
Popis: High density lipoproteins (HDL) protect against ischemia reperfusion injury (IRI). However the precise mechanisms are not clearly understood. The novel intrinsic prosurvival signaling pathway named survivor activating factor enhancement (SAFE) path involves the activation of tumor necrosis factor (TNF) alpha and signal transducer and activator of transcription 3 (STAT3). SAFE plays a crucial role in cardioprotection against IRI. We propose that HDL protect against IRI via activation of the SAFE pathway and modulation of the mitochondrial permeability transition pore (mPTP) opening.Isolated mouse hearts were subjected to global ischemia (35 min) followed by reperfusion (45 min). HDL were given during the first 7 min of reperfusion. In control hearts, the post-reperfusion infarct size was 41.3 ± 2.3%. Addition of HDL during reperfusion reduced the infarct size in a dose-dependent manner (HDL 200 μg protein/ml: 25.5 ± 1.6%, p0.001 vs. control). This protective effect was absent in TNF deficient mice (TNF-KO) or cardiomyocyte-STAT3 deficient mice (STAT3-KO). Similarly, HDL, given as a preconditioning stimulus, improved cell survival and inhibited mPTP opening in isolated cardiomyocytes subjected to simulated ischemia. These protective responses were inhibited in cardiomyocytes from TNF-KO and STAT3-KO mice.Our data demonstrate that HDL protect against IRI by inhibition of mPTP opening, an effect mediated via activation of the SAFE pathway.
Databáze: OpenAIRE
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