Left ventricular expression of lectin-like oxidized low-density lipoprotein receptor-1 during the development of heart failure

Left ventricular expression of lectin-like oxidized low-density lipoprotein receptor-1 during the development of heart failure

Tomohide Takaya1, Tatsuya Morimoto1, Yoichi Sunagawa1, Hiromichi Wada1, Teruhisa Kawamura1, Akira Shimatsu1, Masatoshi Fujita2, Yoshiko Fujita3, Tatsuya Sawamura3, Koji Hasegawa1.

  1. Division of Translational Research, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  3. Department of Vascular Physiology, National Cardiovascular Center, Osaka, Japan.

第73回日本循環器学会学術集会 (大阪), 2009/03/20 (Featured Research Session).

Abstract

Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a receptor for oxLDL and induced by proinflammatory cytokines and oxidative stress. Activated LOX-1 pathway in cardiomyocytes induces apoptosis in vitro and deteriorates ischemia-reperfusion injury in vivo. However, the role of LOX-1 in chronic heart failure remains unknown. We examined left ventricular (LV) expression of LOX-1 in a salt-sensitive Dahl (DS) rat model of hypertension. DS rats exhibited LV hypertrophy a 11 weeks, and decreased systolic function at 18 weeks. LV mRNA levels of LOX-1 indicated a 4.7-fold increase in DS rat compared with control salt-resistant Dahl (DR) rats at 11 weeks, and a 32-fold increase at 18 weeks. Immunohistochemistry illustrated that LOX-1 expression in vessel walls and cardiomyocytes were greater in DS than DR rat hearts. The mRNA levels of LOX-1 were significantly correlated with blood pressure, LV/body weight ratio, LV wall thickness, and LV end-systolic dimension, and strongly correlated with the decrease of ejection fraction (r = -0.77), and BNP levels on plasma (r = 0.74) and mRNA (r = 0.81). Importantly, LV mRNA levels of LOX-1 revealed the strongest correlation with a chemotactic factor MCP-1 (r = 0.94), and proinflammatory cytokines TGF-β1 (r = 0.94) and IL-1β (r = 0.74). These findings demonstrate that LV expression of LOX-1 is markedly increased in DS rat model of hypertension and possibly involved in chronic inflammation during the development of heart failure.