Reduction in Myocardial Ischemia/Reperfusion Injury in Group X Secretory Phospholipase A 2 –Deficient Mice
| العنوان: | Reduction in Myocardial Ischemia/Reperfusion Injury in Group X Secretory Phospholipase A 2 –Deficient Mice |
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| المؤلفون: | Hideo Tezuka, Masaki Kanazawa, Kiyotaka Kugiyama, Yoshikazu Ishimoto, Toshiaki Yano, Takamitsu Nakamura, Ken-ichi Kawabata, Tsuyoshi Kobayashi, Kohji Hanasaki, Yukio Saito, Yasunori Yokota, Noriko Suzuki, Jyun-ei Obata, Daisuke Fujioka |
| المصدر: | Circulation. 117:2977-2985 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Indoles, Myocardial ischemia, Neutrophils, Myocardial Infarction, Myocardial Reperfusion Injury, Acetates, Mice, chemistry.chemical_compound, Physiology (medical), Phosphatidylcholine, Internal medicine, medicine, Animals, Group X Phospholipases A2, Myocytes, Cardiac, Prodrugs, Myocardial infarction, Enzyme Inhibitors, Cells, Cultured, Peroxidase, Arachidonic Acid, business.industry, medicine.disease, Mice, Mutant Strains, Mice, Inbred C57BL, Chemotaxis, Leukocyte, medicine.anatomical_structure, Endocrinology, chemistry, Echocardiography, Immunology, Arachidonic acid, Bone marrow, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, business, Group X Secretory Phospholipase A2, Perfusion, Reperfusion injury |
| الوصف: | Background— Group X secretory phospholipase A 2 (sPLA 2 -X) has the most potent hydrolyzing activity toward phosphatidylcholine and elicits a marked release of arachidonic acid among several types of sPLA 2 . sPLA 2 -X is expressed in neutrophils, but its pathogenic role remains unclear. Methods and Results— We generated mice that lack sPLA 2 -X and studied their response to myocardial ischemia/reperfusion. The sPLA 2 -X −/− mice had a significant reduction in myocardial infarct size and a decrease in myocardial myeloperoxidase activity compared with sPLA 2 -X +/+ mice. Myocardial infarct size was also significantly reduced in lethally irradiated sPLA 2 -X +/+ mice reconstituted with sPLA 2 -X −/− bone marrow compared with sPLA 2 -X +/+ bone marrow. The extent of myocardial ischemia/reperfusion injury was comparable between sPLA 2 -X −/− and sPLA 2 -X +/+ mice in Langendorff experiments using isolated hearts and blood-free perfusion buffer, supporting a potential role of sPLA 2 -X in blood in myocardial ischemia/reperfusion injury. In the infarcted myocardium of sPLA 2 -X +/+ mice, sPLA 2 -X was released from neutrophils but not myocardial tissues and platelets and was undetectable in the peripheral serum. The sPLA 2 -X −/− mice had lower accumulation of neutrophils in ischemic myocardium, and the isolated sPLA 2 -X −/− neutrophils had lower release of arachidonic acid and attenuated cytotoxic activities including respiratory burst compared with sPLA 2 -X +/+ neutrophils. The attenuated functions of sPLA 2 -X −/− neutrophils were reversible by the exogenous addition of sPLA 2 -X protein. Furthermore, administration of a sPLA 2 inhibitor reduced myocardial infarct size and suppressed the cytotoxic activity of sPLA 2 -X +/+ neutrophils. Conclusions— Myocardial ischemia/reperfusion injury was attenuated in sPLA 2 -X −/− mice partly through the suppression of neutrophil cytotoxic activities. |
| تدمد: | 1524-4539 0009-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21a868d00e44602af45c6220158cc793 https://doi.org/10.1161/circulationaha.107.743997 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....21a868d00e44602af45c6220158cc793 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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