Left ventricular expression of LOX-1 during the development of heart failure

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.

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  2. Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  3. Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  4. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  5. 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.