Oxidized LDL (oxLDL) contributes to many atherogenic steps in the vascular wall, but the significance of oxLDL in circulating blood remains unclear. Recent progress in procedures for measuring both human and murine oxLDL has provided growing evidence of the importance of circulating oxLDL.
Circulating oxLDL is elevated in patients with advanced atherosclerosis, such as coronary heart disease and ischemic stroke, and also reflects early atherosclerotic changes and metabolic disorders including diabetes and obesity. In-vitro exposure to oxLDL increased mononuclear cell nuclear factor-κB activity, suggesting a pathogenic role of circulating oxLDL in exacerbation of oxidative stress. In addition, adenoviral administration of secreted scavenger receptor-A1, which functions as a decoy, suppresses foam cell formation in LDL receptor-deficient mice via a blockade of modified LDL incorporation into macrophages. Furthermore, when lectin-like oxLDL receptor-1 was ectopically expressed in the liver, circulating oxLDL was reduced, resulting in complete prevention of atherosclerotic progression in apolipoprotein E-deficient mice. Thus, circulating oxLDL impacts atherogenic formation.
The roles of circulating oxLDL in atherosclerotic pathogenesis are now attracting considerable attention. OxLDL removal from circulating blood is a promising therapeutic strategy against atherosclerosis.
aDivision of Molecular Metabolism and Diabetes, Japan
bDivision of Advanced Therapeutics for Metabolic Diseases, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
Correspondence to Hideki Katagiri, MD, PhD, Division of Advanced Therapeutics for Metabolic Diseases, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan Tel: +81 22 717 8228; fax: +81 22 717 8228; e-mail: firstname.lastname@example.org