NIH 2020 Dec 1;8(12):558. doi: 10.3390/biomedicines8120558. Reverse cholesterol transport refers to the process by which cholesterol is removed from the tissues and returned to the liver. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. Epub 2013 Sep 5. Biochimie. Circulation. eCollection 2020 Aug. Int J Biomed Investig. Regulatory Roles of Related Long Non-coding RNAs in the Process of Atherosclerosis. Arterioscler Thromb Vasc Biol. eCollection 2020. Verdier C, Martinez LO, Ferrières J, Elbaz M, Genoux A, Perret B. Arch Cardiovasc Dis. One area of agreement is that reverse cholesterol transport remains a primary hypothesis for an anti-atherogenic role of HDL. HDL in the high (if not the “extremely high”) range usually correlates with efficient reverse cholesterol transport and has benefits for cardiovascular health, inflammation, antioxidant status etc, but people with HDL outside (higher or lower than) the ideal range can be equally healthy if their overall metabolic health (insulin sensitivity) is good. Schematic presentation of reverse cholesterol…, Schematic presentation of reverse cholesterol transport, Prof. Dr. Hasan Veysi Güneş’s collections, NLM Bioassays that measure cholesterol efflux capacity of HDL (or of apolipoprotein [apo] B-depleted plasma) have emerged as potentially accurate surrogates for reverse cholesterol transport. This review will emphasize 3 major evolving themes regarding HDL metabolism and RCT. J Biomed Res. A major recognized functional property of HDL particles is to elicit cholesterol efflux and consequently mediate reverse cholesterol transport (RCT). In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Potential Link Between Proprotein Convertase Subtilisin/Kexin Type 9 and Alzheimer's Disease. Wang N, Lan D, Chen W, Matsuura F, Tall AR. -, Hansson GK. HDL are heterogeneous particles regarding their sizeand composition. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. The second theme is the critical role that intravascular remodeling of HDL by lipid transfer factors, lipases, cell surface receptors, and non-HDL lipoproteins play in determining the ultimate metabolic fate of HDL and plasma HDL-c concentrations. 2009 Oct;206(2):321-7. doi: 10.1016/j.atherosclerosis.2008.12.044. 2020 Sep 26;12(10):2952. doi: 10.3390/nu12102952. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Clipboard, Search History, and several other advanced features are temporarily unavailable. The high concentration of low-density lipoprotein cholesterol (LDL-c) is an independent risk factor for coronary artery disease. Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins. USA.gov. Wang N, Ranalletta M, Matsuura F, Peng F, Tall AR. 2015 Mar 27;116(7):1133-42. doi: 10.1161/CIRCRESAHA.116.305485. Regulation of reverse cholesterol transport - a comprehensive appraisal of available animal studies Wijtske Annema1,2 and Uwe JF Tietge1,2* Abstract Plasma levels of high density lipoprotein (HDL) cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. doi: 10.1016/j.heliyon.2020.e04788. In this video, I have explained HDL synthesis as a nascent HDL and maturation of HDL. The RCT pathway consists of the following steps: 1. Takiguchi S, Ayaori M, Yakushiji E, Nishida T, Nakaya K, Sasaki M, Iizuka M, Uto-Kondo H, Terao Y, Yogo M, Komatsu T, Ogura M, Ikewaki K. Arterioscler Thromb Vasc Biol. Reverse cholesterol transport is facilitated by high-density lipoprotein (HDL) metabolism. J Mol Med (Berl). Lipoproteins containing apoA-I [high-density lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. Nuclear receptors of the RXR heterodimer family have recently been shown to regulate key genes involved in HDL metabolism and reverse cholesterol transport. 2020 Aug 30;6(8):e04788. Epub 2006 Feb 25. HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular cholesterol export. Please enable it to take advantage of the complete set of features! Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. Biomedicines. My position is that reverse cholesterol transport has to be important because of this incredible architecture of receptors and transport proteins that have built up around the role of HDL and reverse cholesterol transport. C, cholesterol; CE, cholesteryl ester; LCAT, lecithin cholesterol ethyl transferase; PL, phospholipid; ApoA-1, apolipoprotein A-1. A cell cannot metabolize cholesterol to energy theway it -.  |  Epub 2015 Jan 14. 2009 Jun;11(6):534-43. doi: 10.1111/j.1463-1326.2008.01012.x. The metabolism of high-density lipoproteins (HDL), which are inversely related to risk of atherosclerotic cardiovascular disease, involves a complex interplay of factors regulating HDL synthesis, intravascular remodeling, and catabolism. the transport of cholesterol from peripheral cells back to the liver for metabolism and biliary excretion, in insulin resistance and type 2 diabetes mellitus. The third theme is the growing appreciation that insulin resistance underlies the majority of cases of low HDL-c in humans and the mechanisms by which insulin resistance influences HDL metabolism. 1.  |  See this image and copyright information in PMC. Co-Administration of Propionate or Protocatechuic Acid Does Not Affect DHA-Specific Transcriptional Effects on Lipid Metabolism in Cultured Hepatic Cells. Compared with other lipoproteins, they have thehighest relative density while being smallest in size. The therapeutic approaches include CETP inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic farnesoid X receptor agonists, and gene therapy. A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Cholesterol transport and pathways, drugs used for treatment of atherosclerosis. Drug Deliv. Furthermore, although efflux of cholesterol from macrophages represents only a tiny fraction of overall cellular cholesterol efflux, it is the most important with regard to atherosclerosis, suggesting that it be specifically termed macrophage RCT. Epub 2004 Jun 21. Epub 2018 May 10. Postprandial dyslipidemia in insulin resistant states in adolescent populations. 2014 Jan;96:56-66. doi: 10.1016/j.biochi.2013.08.027. 2005;352:1685–95. Ann Epidemiol. 2020 Oct 19;11:564604. doi: 10.3389/fphys.2020.564604. 2004 Jun 29;101(26):9774-9. doi: 10.1073/pnas.0403506101. Kudinov VA, Alekseeva OY, Torkhovskaya TI, Baskaev KK, Artyushev RI, Saburina IN, Markin SS. -, Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. Li J, Han M, Li J, Ge Z, Wang Q, Zhou K, Yin X. 2020 Jan 30;34(5):328-342. doi: 10.7555/JBR.34.20190094. 1978;47:751–7. in reverse cholesterol transport. Clipboard, Search History, and several other advanced features are temporarily unavailable. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. 96.3.2 High-Density Lipoprotein (HDL) Metabolism “ Reverse cholesterol transport ” (RCT) describes cholesterol transport in HDL from peripheral cells back to the liver for secretion in bile (17). The initial step in HDL metabolism involves the formation of small lipid-poor nascent HDL … -, Lusis AJ, Fogelman AM, Fonarow GC. Reverse cholesterol transport (RCT) may counteract the pathogen … Both alterations of lipid/lipoprotein metabolism and inflammatory events contribute to the formation of the atherosclerotic plaque, characterized by the accumulation of abnormal amounts of cholesterol … NIH HHS Cholesterol efflux from peripheral tissues to plasma, 2. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. 2020 Oct 14;21(20):7606. doi: 10.3390/ijms21207606. have recently discussed the effects of flavonoids on reverse cholesterol transport (RCT), high-density lipoprotein (HDL) metabolism, and HLD function [46]. 2020 Nov 19;21(22):8737. doi: 10.3390/ijms21228737. 2004;110:1868–73. Regulation of cholesterol levels is a complicated process, involving cholesterol uptake, biosynthesis, transport, metabolism, and secretion, and has been well described in several recent reviews. The individual lipid and apolipoprotein components of HDL are mostly assembled after secretion, are frequently exchanged with or transferred to other lipoproteins, are actively remodeled within the plasma compartment, and are often cleared separately from one another. Nature. The science behind the GOOD and BAD cholesterol. 2002;420:868–74. COVID-19 is an emerging, rapidly evolving situation. Simplified model of Reverse Cholesterol Transport -HDL is made in the blood from Apo A1 that is secreted from the liver -ApoA1 responds to lipid rich meal -ApoA1 forms a pre beta HDL particle (should be more of a flattened shape; it's nascent) 2006 Jun;26(6):1310-6. doi: 10.1161/01.ATV.0000218998.75963.02. This review will emphasize 3 major evolving themes regarding HDL metabolism … HDL (reverse cholesterol transport) lipoproteins are made of a ____ core that consists of _____ and esterified _____ hydrophobic triglycerides ... role of liver in cholesterol metabolism - Formation of bile salts - Enterohepatic circulation of free cholesterol and bile. NCI CPTC Antibody Characterization Program, Smith LC, Pownall HJ, Gotto AM., Jr The plasma lipoproteins: structure and metabolism. The cardioprotective role of HDL is thought to be related at least in part to the role of HDL in reverse cholesterol transport (RCT), the process by which cholesterol is removed from peripheral cells and transported to the liver for metabolism and excretion in the bile [ 13, 14 ]. Computational SNP Analysis and Molecular Simulation Revealed the Most Deleterious Missense Variants in the NBD1 Domain of Human ABCA1 Transporter. Thus, malfunction in HDL turnover during reverse cholesterol transport may contribute to the buildup of atherosclerotic plaques, and subsequent cardiovascular disease in insulin resistant individuals. -, Libby P. Inflammation in atherosclerosis. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. 2020 Aug 30;21(17):6275. doi: 10.3390/ijms21176275. HHS  |  This review describes abnormalities in HDL metabolism and reverse cholesterol transport, i.e. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Eur J Clin Invest. 2003 Dec;33(12):1051-69. doi: 10.1111/j.1365-2362.2003.01263.x. Progress in our understanding of HDL metabolism and macrophage reverse cholesterol transport will increase the likelihood of developing novel therapies to raise plasma HDL concentrations and promote macrophage RCT and in proving that these new therapeutic interventions prevent or cause regression of atherosclerosis in humans. Sterically stabilized recombined HDL composed of modified apolipoprotein A-I for efficient targeting toward glioma cells. Du XM, Kim MJ, Hou L, Le Goff W, Chapman MJ, Van Eck M, Curtiss LK, Burnett JR, Cartland SP, Quinn CM, Kockx M, Kontush A, Rye KA, Kritharides L, Jessup W. Circ Res. Theyeffectively function in homeostasis and lipid metabolism. N Engl J Med. Author information. 1992;2:23–8. First, via interactions of HDL with hepatocyte scavenger receptor class B ( SR-BI ), cholesterol is selectively taken up by the liver. Annu Rev Biochem. 2 authors. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Int J Mol Sci. 2 RCT is defined as the process by … Results of clinical trials should be awaited before further clinical management of atherosclerotic cardiovascular disease. Meng Q, Pu L, Luo X, Wang B, Li F, Liu B. 2020 Dec;27(1):530-541. doi: 10.1080/10717544.2020.1745330. HDL is believed to play a key role in the process of reverse cholesterol transport (RCT), in which it promotes the efflux of excess cholesterol from peripheral tissues and returns it to the liver for biliary excretion. HDL have animportant role in carrier in reverse cholesterol transport (RCT)and act as a carrier of cholesterol back to the liver. 2018;1(1):106. doi: 10.31531/2581-4745.1000106. Millar CL 1, Duclos Q 1, Blesso CN 2. The first theme is that HDL is a universal plasma acceptor lipoprotein for cholesterol efflux from not only peripheral tissues but also hepatocytes, which are a major source of cholesterol efflux to HDL. Int J Mol Sci. Apolipoprotein A-II is a key regulatory factor of HDL metabolism as appears from studies with transgenic animals and clinical outcomes. Please enable it to take advantage of the complete set of features! Reverse cholesterol transport pathway. LXR-induced redistribution of ABCG1 to plasma membrane in macrophages enhances cholesterol mass efflux to HDL. 2013 Nov;106(11):601-11. doi: 10.1016/j.acvd.2013.06.052. Hepatic Overexpression of Endothelial Lipase Lowers High-Density Lipoprotein but Maintains Reverse Cholesterol Transport in Mice: Role of Scavenger Receptor Class B Type I/ATP-Binding Cassette Transporter A1-Dependent Pathways. Targeting HDL Metabolism and Reverse Cholesterol Transport. Millar et al. Genetic basis of atherosclerosis: part I: new genes and pathways. cholesterol in liver. HDL helps in reverse cholesterol transport from extrahepatic tissues to the liver. It competes with plasminogen by binding sites, reducing the plasmin generation and inhibiting fibrinolysis, therefore, the thrombus form… Epub 2013 Sep 25. Lipoproteins containing apoA-I [high- density lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. 1 This landmark discovery inspired investigations into the mechanisms by which HDL confers atheroprotection, leading to the identification of the reverse cholesterol transport (RCT) pathway. Reverse cholesterol transport in type 2 diabetes mellitus. Front Physiol. HDL that contains apolipoprotein E (apoE) is a subspecies especially active in steps in reverse cholesterol transport, a process that brings cholesterol from peripheral cells to the liver.  |  Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream. M01 RR00040/RR/NCRR NIH HHS/United States. Mokkala K, Juhila J, Houttu N, Sorsa T, Laitinen K. Heliyon. COVID-19 is an emerging, rapidly evolving situation. High-Density Lipoproteins as Homeostatic Nanoparticles of Blood Plasma. Inflammation, atherosclerosis, and coronary artery disease. Increasing the circulating levels of HDL, as well as the efficiency of the RCT process, could result in a reduction in the development of coronary artery disease and atherosclerosis. Targeting high-density lipoproteins: update on a promising therapy. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. The Framingham Heart Study in the 1960s was the first study to report inverse associations between cardiovascular risk and plasma HDL-C (high-density lipoprotein cholesterol). Elucidations of HDL metabolism give rise to therapeutic targets wit h po-tential to raising plasma HDL cholesterol levels, thereby reducing the risk of developing CHD. Epub 2009 Jan 19. LCAT-mediated esterification of cholesterol and remodeling of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and 4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated transfer There are several established strategies for raising HDL cholesterol in humans, such as lifestyle changes; use of drugs including fibrates, statins, and niacin; and new therapeutic approaches. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. HDL Metabolism: Reverse cholesterol transport.  |  The Framingham Study. Pathophysiology of Type 2 Diabetes Mellitus. HDL heterogeneity is the result of the activity of several factors that assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1 (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP), endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). USA.gov. Physical inactivity contributes to increased cardiovascular diseases, such as atherosclerosis, which are leading causes of death worldwide (Rosamond et al., 2008). Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. Affiliations. Proc Natl Acad Sci U S A. Cholesterol from non-hepatic peripheral tissues is transferred to HDL by the ABCA1 ( ATP-binding cassette transporter ). NLM Epub 2018 Mar 27. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Second, cholesteryl ester transfer protein ( CETP) mediates the transfer of cholesteryl esters from HDL to apoB-containing lipoproteins in exchange for triglycerides. 2018 Jul;38(7):1454-1467. doi: 10.1161/ATVBAHA.118.311056. Diabetes Obes Metab. Epub 2009 Mar 21. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge. Int J Mol Sci. Plasma levels of high density lipoprotein (HDL) cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. Are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease is to cholesterol. 2009 Jun ; 26 ( 6 ):1310-6. doi: 10.1161/01.ATV.0000218998.75963.02 of agreement is that reverse cholesterol (. Key genes involved in HDL metabolism as appears from studies with transgenic animals clinical! Receptor class B ( SR-BI ), antioxidant, anti-inflammatory, and charge atherosclerosis... 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