ATHEROSCLEROSIS: CELL BIOLOGY AND LIPOPROTEINS: Edited by Mohamad Navab and Menno de WintherTransport of LDLs into the arterial wall: impact in atherosclerosisZhang, Xinboa,b; Fernández-Hernando, Carlosa,b,cAuthor Information aVascular Biology and Therapeutics Program bIntegrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine cDepartment of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA Correspondence to Carlos Fernández-Hernando, PhD, 10 Amistad Street, Amistad Research Building, Room 337C, New Haven, CT 06510, USA. Tel: +1 203 737 4615; fax: +1 203 737 2290; e-mail: [email protected]; Xinbo Zhang, MD, PhD, 10 Amistad Street, Amistad Research Building, Room 320, New Haven, CT 06510, Yale University School of Medicine. Tel: +1 203 737 3300; fax: +1 203 737 2290; e-mail: [email protected] Current Opinion in Lipidology: October 2020 - Volume 31 - Issue 5 - p 279-285 doi: 10.1097/MOL.0000000000000701 Buy Metrics Abstract Purpose of review Atherosclerosis is a complicated cardiovascular disease characterized by unbalanced lipid metabolism and unresolved inflammation that occurred inside of arteries. The transcytosis of LDL across the endothelium and its accumulation in the arterial wall is the initial step of atherosclerosis. Here, we summarize recent research into the understanding of the regulatory mechanisms of endothelial LDL transcytosis and its relevance in the development of atherosclerosis. Recent findings A number of recent studies have revealed the contribution of caveolae, activin-like kinase 1 (ALK1) or scavenger receptor B1 (SR-B1) in endothelial LDL transcytosis and the progression of atherosclerosis. Caveolin-1 (Cav-1), the major protein component in caveolae, is required for the formation of caveolae and caveolae-mediated LDL uptake and transcytosis across the endothelium. SR-B1 and ALK1 directly bind LDL and facilitate the transport of LDL through the endothelial cells. The change in expression of caveolae-associated proteins and SR-B1 regulates endothelial LDL transcytosis and the pathogenesis of atherosclerosis. Summary Caveolae, ALK1 and SR-B1 are identified as key regulators in the LDL transcytosis across the endothelium. Endothelial LDL transcytosis might be a potential therapeutic approach to limit the initiation of early atherosclerosis and treat the atherosclerotic vascular diseases. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.