Sm by which cholesterol excess is transported from cells of extrahepat…

Sm by which cholesterol excess is transported from cells of extrahepatic tissues and carried back to the liver, where it can be eliminated or recycled. There has been a rising interest in the physiology and pharmacology of RCT [2]. However, contrary to what has been achieved in the field of LDL control through statin therapy, pharmacological modulation of HDL biology has not achieved a comparable success in the clinical arena. Nevertheless, this growing burden of knowledge has yielded a new generation of drugs which are under clinical evaluation and are able not only to increase HDL levels and function, but also to achieve a measurable atherosclerotic plaque regression. Within these drugs, apo-AI Milano analogs and CETP (Cholesterol ester transfer protein) inhibitors dalcetrapib and anacetrapib deserve to be highlighted according to the state-of-the-art clinical evidence. Reverse cholesterol transport (RCT) Early in the 80's it was demonstrated that HDL can act as an acceptor of cellular cholesterol, the first step in the pathway known as RCT [3]. Briefly, HDL precursors (lipid-free apoA-I or lipid-poor pre-b1-HDL) 2,2,3,3-Tetrafluoropropyl N,N'-diethylcarbamimidothioate trifluoromethanesulfonate are produced by the liver, the intestine or are released from lipolysed VLDL and chylomicrons. PLTP (Phospholipid transfer protein)-mediated phospholipid transfer facilitates apo-AI lipidation and the formation of pre-b-HDL [2]. Lecithin cholesterol acyl-transferase (LCAT) esterifies cholesterol in HDL [4]. Cholesterol esters, more hydrophobic than free cholesterol, move into the core of HDL particle, creating a gradient PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13867361 that enables HDL to accept free cholesterol. After scavenging cholesterol from peripheral tissues, HDL transports cholesterol to the liver where it will be excreted or recycled. The selective uptake of cholesterol esters from HDL into hepatocytes is mediated by the scavenger PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3081428 receptor B type I (SR-BI) [2], and facilitated by the ATP binding cassette (ABC) transporters ABCA1 and ABCG1 [4]. However, cholesterol esters may also be transferred from HDL to other lipoproteins, including chylomicrons, VLDL and LDL, a process mediated by the CETP. Therefore, CETP possesses a potential atherogenic role by enhancing the transfer of cholesterol esters from antiatherogenic lipoproteins (HDL) to proaterogenic ones (mainly LDL). A summary of HDL regulation is shown in the Figure 1. Effects of HDL* Correspondence: santiredondo@hotmail.com 1 Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Spain Full list of author information is available at the end of the articleAntiatherosclerotic effects of HDLAtheromatous plaques are not irreversible lesions. Indeed, pioneer experimental studies have demonstrated?2011 Redondo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Redondo et al. Lipids N-BOC-3-Fluoro-D-phenylalanine in Health and Disease 2011, 10:175 http://www.lipidworld.com/content/10/1/Page 2 ofFigure 1 Simplified scheme of reverse cholesterol transport. In the onset and ijms17122034 progression of atherosclerotic lesions the uptake of modified LDL (mainly oxidized LDL or oxLDL) by macrophages through a process mediated by scavenger receptors (i.e. SR-A and CD36) that lead to the formation of lipid-loaded cells is critical. This seems to be a reversible process, as HDL-mediated RC.