Oxidized LDL receptors: a recent update

• Published in: Current opinion in lipidology Vol. 34; no. 4; p. 147
• Main Authors: Khan, Mohd Azeem, Mohammad, Irshad, Banerjee, Sohom, Tomar, Akanksha, Varughese, Kottayil I, Mehta, Jawahar L, Chandele, Anmol, Arockiasamy, Arulandu
• Format: Journal Article
• Language: English
• Published: England 01.08.2023
• Subjects: Atherosclerosis - metabolism; Humans; Inflammation; Lipoproteins, LDL - metabolism; Plaque, Atherosclerotic; Receptors, LDL; Receptors, Oxidized LDL; Scavenger Receptors, Class E - metabolism
• ISSN: 1473-6535
• DOI: 10.1097/MOL.0000000000000884

LDL in its oxidized form, or 'oxLDL', is now generally acknowledged to be highly proatherogenic and to play a significant role in atherosclerotic plaque formation. Therefore, there has been increasing interest in understanding the significance of oxLDL and its receptors in different phases of atherosclerosis, leading to the accumulation of additional data at the cellular, structural, and physiological levels. This review focuses on the most recent discoveries about these receptors and how they influence lipid absorption, metabolism, and inflammation in various cell types. Two crystal structures of lectin-like oxLDL receptor-1 (LOX-1), one with a small molecule inhibitor and the other with a monoclonal antibody have been published. We recently demonstrated that the 'surface site' of LOX1, adjacent to the positively charged 'basic spine region' that facilitates oxLDL binding, is a targetable site for drug development. Further, recent human studies showed that soluble LOX-1 holds potential as a biomarker for cardiovascular disease diagnosis, prognosis, and assessing the efficacy of therapy. Receptor-mediated oxLDL uptake results in cellular dysfunction of various cell types involved in atherogenesis and plaque development. The current advancements clearly demonstrate that targeting oxLDL-LOX-1 axis may lead to development of future therapeutics for the treatment of atherosclerotic cardiovascular and cerebrovascular diseases.