Left ventricular expression of LOX-1 is markedly increased in proportion to the extent of hypertension-induced heart failure in rats

Left ventricular expression of LOX-1 is markedly increased in proportion to the extent of hypertension-induced heart failure in rats

Tomohide Takaya1, Tatsuya Morimoto1, Yoichi Sunagawa1, Hiromichi Wada1, Teruhisa Kawamura1, Akira Shimatsu1, Masatoshi Fujita3, Yoshiko Fujita2, Tatsuya Sawamura2, Koji Hasegawa1.

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

第12回日本心不全学会学術集会 (東京), 2008/10/17 (ポスター).

Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was originally identified as an endothelial receptor for oxidized LDL and now recognized as a multi-ligand receptor. LOX-1 expression in cardiomyocytes can be induced by oxidative stress and by various hormonal stimuli. Activation of LOX-1 pathway in cardiomyocytes induces apoptosis of these cells. However the role of LOX-1 in the development of heart failure in vivo is unknown. We examined left ventricular (LV) expression of LOX-1 in salt-sensitive Dahl (DS) rat model of hypertension. Compared with control salt-resistant Dahl rats, high-salt diet resulted in hypertension and apparent concentric LV hypertrophy by echocardiography in DS rats. LV systolic function were preserved at 11 weeks, and decreased at 18 weeks. Quantitative real-time PCR revealed increase in LV levels of LOX-1 mRNA in DS rats compared with DR rats by 4.7-fold at 11 weeks and by 32-fold at 18 weeks. LV LOX-1 mRNA levels were significantly correlated with LV end-systolic dimension (R = 0.640, p = 0.0002) and LV posterior wall thickness (R = 0.555, p = 0.0022). Importantly, LOX-1 levels were strongly correlated with decrease in LV ejection fraction (R = 0.774, p < 0.0001) and increase in mRNA levels of BNP (R = 0.814, p < 0.0001), a representative marker of LV wall stress and heart failure. These findings demonstrate that LV expression of LOX-1 is markedly increased in proportion to the extent of hypertension-induced heart failure.