Left ventricular expression of LOX-1 during the development of heart failure
Tomohide Takaya1,2, Hiromichi Wada2, Tatsuya Morimoto2, Yoichi Sunagawa2, Teruhisa Kawamura2, Akira Shimatsu3, Yoshiko Fujita4, Masatoshi Fujita5, Tatsuya Sawamura4, Koji Hasegawa2.
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- Department of Vascular Physiology, National Cardiovascular Center Research Institute, Osaka, Japan.
第32回心筋代謝研究会 (大阪), 2009/07/05 (口演).
Abstract
Background: Lectin-like oxidized LDL receptor-1 (LOX-1) is induced by proinflammatory cytokines and oxidative stress. LOX-1 activation induces cardiac apoptosis and deteriorates ischemia-reperfusion injury. However, the role of LOX-1 in chronic heart failure (CHF) remains unknown.
Methods and Results: We examined the left ventricular (LV) expression of LOX-1 in a DS rat model of hypertension. Compared with control DR rats, mRNA levels of LOX-1 increased by 4.7-fold in DS rats at the age of 11 weeks with LV hypertrophy (LVH), and by 32-fold at 18 weeks with a decreased systolic function. LOX-1 expression in vessel walls and cardiomyocytes were greater in DS than DR rats at 18 weeks. LOX-1 expression was correlated with the decrease in EF and with the increase of BNP. LOX-1 expression showed the strongest corrleations with MCP-1 and TGF-β1 expression. Furthermore, serum levels of soluble LOX-1 were significantly increased in CHF patients with LVH compared with healthy subjects. These results suggest that LOX-1 will be useful as a biomarker of CHF.