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Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial ischemia/reperfusion injury.
MedLine Citation:
PMID:  23129587     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: Transient receptor potential melastatin 2 (TRPM2) highly expressed in immunocytes is a Ca(2+)-permeable nonselective cation channel activated by oxidative stress. Myocardial ischemia/reperfusion (I/R) injury is characterized by acute inflammation associated with the augmentation of oxidative stress. We hypothesized that TRPM2 is implicated in the exacerbation of myocardial I/R injury.Methods and ResultsWildtype (Trpm2(+/+)) and Trpm2 knockout (Trpm2(-/-)) mice were subjected to ligation of the left main coronary artery followed by reperfusion. Myocardial infarction following I/R, but not ischemia alone, was more reduced in Trpm2-/- mice than in Trpm2(+/+) mice and cardiac contractile functions were also improved in Trpm2(-/-) mice. TRPM2 was highly expressed in the polymorphonuclear leukocytes (PMNs) rather than in the heart. The number of neutrophils and myeloperoxidase (MPO) activity in the reperfused area following ischemia was lowered in Trpm2(-/-) mice. When Trpm2+(/+) or Trpm2(-/-) PMNs were administered to the Trpm2(-/-) heart ex vivo through the perfusate or in vivo by intravenous injection, Trpm2(+/+) PMNs produced enlargement of the infarct size. Following in vitro regional I/R, a pharmacological inhibitor of TRPM2 reduced the infarct size. The combination of H(2)O(2) and leukotriene B(4) (LTB(4)) increased intracellular Ca(2+) concentration and their adhesion to endothelial cells in Trpm2(+/+) but not in Trpm2(-/-) PMNs. CONCLUSIONS: These findings indicate that neutrophil TRPM2 is implicated in the exacerbation of myocardial reperfusion injury. Accumulation of neutrophils in the reperfused area mediated by TRPM2 activation is likely to play a crucial role in myocardial I/R injury.
Authors:
Toshihito Hiroi; Teruaki Wajima; Takaharu Negoro; Masakazu Ishii; Yasuko Nakano; Yuji Kiuchi; Yasuo Mori; Shunichi Shimizu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-5
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pathophysiology, Showa University School of Pharmacy, Shinagawa-ku, Tokyo 142-8555, Japan.
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