Abstract 3563: Soluble Lectin-like Oxidized Low-density Lipoprotein Receptor-1 is Increased in Sera From Chronic Heart Failure Patients With Left Ventricular Hypertrophy
Background: Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) was originally identified as an endothelial receptor for oxLDL, and is now recognized as a multi-ligand receptor. LOX-1 expression in cardiomyocytes can be induced by oxidative stress and various hormonal stimuli. Using a salt-sensitive Dahl rat model of hypertension, we showed that the left ventricular (LV) expression of LOX-1 was markedly (~30 fold) increased in proportion to the degree of heart failure. LV mRNA levels of LOX-1 were significantly (p<0.0001) correlated with the decrease in the ejection fraction (EF) (r=0.772) and with increases in plasma (r=0.744) and LV mRNA (r=0.814) levels of BNP. In addition, LV LOX-1 levels were closely correlated with LV mRNA levels of inflammatory cytokines such as MCP-1 (r=0.943), IL-1β (r=0.760), and TGF-β1 (r=0.936). The membrane-proximal extracellular domain of LOX-1 can be proteolytically cleaved and released into the blood stream in a soluble form (sLOX-1). As an initial step to determine the clinical significance of sLOX-1 in chronic heart failure (CHF), we carried out a cross-sectional study.
Methods and Results: We measured the levels of sLOX-1 in sera from CHF patients with LV hypertrophy (CHF-LVH). Apparently healthy subjects with normal LV dimensions and systolic function served as controls. There were no significant differences in the age, body mass index, systolic and diastolic blood pressures, and heart rate between CHF-LVH and control groups. However, the LV end-diastolic dimension (CHF-LVH, 64±5 vs. control, 42±1 mm) and LV mass index (157±26 vs. 72±2 g/m2) were significantly larger, and EF (38±3 vs. 72±2 %) was significantly lower in the CHF-LVH than the control group. Enzyme-linked immunosorbent assays revealed that serum levels of sLOX-1 were significantly increased in the CHF-LVH compared to the control group (948±208 vs. 435±57 pg/mL, respectively, p<0.05).
Conclusions: We provide the first evidence that serum levels of a soluble form of LOX-1 are increased in CHF patients with LV hypertrophy. These findings support the need for further investigations to assess the clinical utility and prognostic value of serum levels of sLOX-1 in patients with CHF.