Abstract 12822: Increased Expression and Serum Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Patients With Aortic Valve Stenosis

Abstract

Background: The development of aortic valve stenosis (AS) involves multiple events, including inflammation and lipid deposition and oxidation. Circulating levels of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) play an important role in the development and progression of atherosclerosis. The aims of this study were to investigate the serum levels of sLOX-1 in patients with AS and also examine the expression of LOX-1 immunohistochemically in aortic valve specimens from these patients. Methods: Serum sLOX-1 levels were measured in patients with AS (n=128), stable angina pectoris (SAP, n=343) and in 53 control subjects using a sandwich ELISA method. Frozen aortic valve samples were also obtained surgically from a cohort of 20 AS patients. In addition, frozen aortic valve specimens were obtained at autopsy from individuals who died of non-cardiovascular causes (n = 11, mean age 68 yr) as a reference. Immunostaining of the samples was performed using antibodies against smooth muscle cells, macrophages, T-lymphocytes, neutrophils, microvessels, and LOX-1. Results: Serum sLOX-1 levels were significantly higher in AS patients compared with SAP patients ( P <0.0005) or control subjects ( P <0.0001). There were no differences in serum sLOX-1 levels between AS patients with or without coronary artery disease. Immunohistochemical staining showed that the LOX-1-positive area, as a percentage of the total area, was significantly (P<0.01) higher in AS patients compared with reference cases. Double immunostaining for LOX-1 and macrophages revealed that the vast majority of LOX-1-positive cells were macrophages. Conclusions: This study demonstrates for the first time that serum sLOX-1 levels are elevated in patients with AS, and AS lesions contain a significantly higher percentage of LOX-1-positive macrophages. These findings suggest that LOX-1, a marker of oxidative stress, may play an important role in the development of aortic valve stenosis.