title: LOX-1 abrogation reduces myocardial ischemia-reperfusion injury in mice.
abstract: LOX-1 is a newly described lectin-like receptor for oxidized-LDL (ox-LDL), which is over-expressed in the ischemic myocardium. To examine the pathogenic role of LOX-1 in the determination of ischemia-reperfusion (I-R) injury to the heart, we developed LOX-1 knockout (KO) mice, and subjected these mice to 60 min of left coronary artery occlusion followed by 60 min of reperfusion. I-R in the LOX-1 KO mice resulted in a significant reduction in myocardial injury as well as in accumulation of inflammatory cells in the I-R myocardium and lipid peroxidation (P<0.01 vs. wild-type mice). Concomitantly, there was significant preservation of cardiac function in the LOX-1 KO mice despite I-R (P<0.01 vs. the wild-type mice). The phosphorylation of oxidative stress-sensitive mitogen-activated protein kinase (p38MAPK) and protein kinase B/Akt-1, expression of nitrotyrosine and inducible nitric oxide synthase (iNOS), and superoxide dismutase activity were enhanced during I-R in the wild-type mice. These alterations in p38MAPK, Akt-1 and iNOS were much less pronounced in the LOX-1 KO mice. The superoxide dismutase activity increased further in the LOX-1 KO mice. These observations provide compelling evidence that LOX-1 may be a key modulator of myocardial I-R injury, and its effect is mediated by pro-oxidant signals. LOX-1 may be a potential target for therapy of myocardial ischemic injury.
authors.affiliation: Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, AR 72205-7199, USA.
authors.forename: Changping
authors.initials: C
authors.lastname: Hu
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.forename: Abhijit
authors.initials: A
authors.lastname: Dandapat
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kawase
authors.forename: Kou-ichi
authors.initials: K
authors.lastname: Jishage
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Dayuan
authors.initials: D
authors.lastname: Li
authors.forename: Paul L
authors.initials: PL
authors.lastname: Hermonat
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D052279:Creatine Kinase, MB Form / Q000097:blood; D017353:Gene Deletion; D006439:Hemodynamics; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000172:deficiency*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D052279:Creatine Kinase, MB Form