Abstract 835: Left Ventricular Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Serves as a Biomarker of Heart Failure in the Salt-Sensitive Dahl Rat Model of Hypertension
Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) was originally identified as an endothelial receptor for oxidized LDL, and now is recognized as a multi-ligand receptor. LOX-1 expression in cardiomyocytes can be induced by oxidative stress and various hormonal stimuli. Activation of the 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 is unknown. We examined the left ventricular (LV) expression of LOX-1 in a salt-sensitive Dahl (DS) rat model of hypertension. Compared with control salt-resistant Dahl (DR) rats, a high-salt diet, started at the age of 6 weeks, induced marked hypertension and apparent concentric LV hypertrophy on echocardiography in DS rats. The LV hypertrophy was moderate at the age of 11 weeks and marked at 18 weeks. The LV systolic function was preserved at 11 weeks, and decreased at 18 weeks. Quantitative real-time PCR revealed a 4.7-fold increase in LV levels of LOX-1 mRNA in DS rats compared with DR rats at 11 weeks, and a 32-fold increase at 18 weeks. The LV LOX-1 mRNA levels were significantly correlated with the LV end-systolic dimension (R=0.640, p=0.0002), and LV posterior wall thickness (R=0.555, p=0.0022), as well as the LV/body weight ratio (R=0.647, p=0.0002), and systolic blood pressure (R=0.751, p<0.0001). LOX-1 levels were also connected with an increase in LV mRNA levels of heme oxygenase-1 (R=0.692, p<0.0001), a marker of oxidative stress. Importantly, LOX-1 levels were strongly associated with a decrease in the LV ejection fraction (R=0.774, p<0.0001) and an increase in mRNA levels of BNP (R=0.814, p<0.0001), a representative marker of LV wall stress and heart failure. Immunohistochemistry demonstrated LOX-1 expression in cardiomyocytes as well as vessel walls of both DS and DR rat hearts. However, expression in cardiomyocytes was greater in DS than in DR. These findings demonstrate that LV cardiomyocyte expression of LOX-1 is markedly increased in proportion to the extent of heart failure and possibly involved in the deterioration of systolic function in the DS rat model of hypertension.