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LOX-1 abrogation reduces myocardial ischemia–reperfusion injury in mice
- Source :
-
Journal of Molecular & Cellular Cardiology . Jan2008, Vol. 44 Issue 1, p76-83. 8p. - Publication Year :
- 2008
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *ISCHEMIA
*MYOCARDIUM
*PROTEIN kinases
*MICE
Subjects
Details
- Language :
- English
- ISSN :
- 00222828
- Volume :
- 44
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular & Cellular Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 28113440
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2007.10.009