Molecular physiology of reverse cholesterol transport. The reverse cholesterol transport pathway improves understanding of genetic networks for fat deposition and muscle growth in beef cattle tyler f. Micrornas mirnas are small, noncoding rnas that have the ability to posttranscriptionally regulate gene expression. Reverse cholesterol transport rct is a pivotal pathway involved in the return of excess cholesterol from peripheral tissues to the liver for excretion in the bile and eventually the feces. Reverse cholesterol transport rct refers to the mobilization of cholesterol on hdl particles hdlc from extravascular tissues to plasma, ultimately for fecal excretion. Highdensity lipoprotein metabolism and reverse cholesterol transport.
Also, cholesteryl ester transfer protein cetp can transfer cholesterol ester particles of hdlc to other lipoproteins grandjean et al. Acceptor specificity and effect of brefeldin on lipid efflux. P2y receptor is critical for reverse cholesterol transport. The role of reverse cholesterol transport in animals and. It is believed to be a critical mechanism by which hdl exert a protective effect on the development of atherosclerosis. After two weeks of voluntary wheel running average 10. Pdf consistent effects of genes involved in reverse. Foremost among these is the minimal involvement of lecithin. Plasma lipoproteins lipoprotein class major lipid class apolipoproteins source cm. Reverse cholesterol transport rct is a term used to describe the efflux of excess cellular cholesterol from peripheral tissues and its return to the liver for excretion in the bile and ultimately the feces. Highdensity lipoprotein function, dysfunction, and reverse. Voluntary exercise increases cholesterol efflux but not.
A major recognized functional property of hdl particles is to elicit cholesterol efflux and consequently mediate reverse cholesterol transport rct. The role of reverse cholesterol transport in animals and humans and. H uman highdensity lipoprotein hdl is a heterogeneous collection of lipoprotein particles with a density between 1. Cholesterol is an important component of the cell membranes, including organelle membranes inside the. Hepatic overexpression of srbi, which mediates the selective uptake of hdl cholesterol, increases macrophagetofeces rct in mice 109. Multiple lines of evidence support that enhancing foam cell cholesterol efflux by hdl highdensity lipoprotein particles, the first step of reverse cholesterol transport rct, is a promising antiatherogenic strategy. Reverse cholesterol transport rct is one pathway for removing excessive cholesterol from extrahepatic cells and tissues and eventual transport to the liver for excretion thus reducing the. Reverse cholesterol transport is a mechanism by which excess cellular cholesterol is transported via lipoproteins in the plasma to the liver where it can be excreted from the body in the feces.
Highdensity lipoprotein hdl is a proteinlipid nanoparticle that has predominately been characterized by its cholesterol concentration hdlc. Hdl cholesterol, of high density lipoprotein cholesterol is called good cholesterol. Lipoproteins containing apoai highdensity lipoprotein hdl are key mediators in rct, whereas nonhighdensity lipoproteins nonhdl, lipoproteins containing apob are involved in the lipid delivery pathway. Reverse cholesterol transport is a term that comprises all the different steps in cholesterol metabolism between cholesterol efflux from macrophage foam cells and the final excretion of cholesterol into the feces either as neutral sterols or after metabolic conversion into. Reverse cholesterol transport rct is a pathway transporting cholesterol from extrahepatic cells and tissues to the liver, and perhaps intestine, for excretion. Rct begins with the removal of cholesterol from arterial foam cells that are of vascular smooth muscle cell vmac or macrophage origin left. Cholesterol plays an indispensable role in regulating the properties of cell membranes in mammalian cells. Plasma levels of high density lipoprotein hdl cholesterol are strongly inversely correlated to the risk of atherosclerotic cardiovascular disease. Cholesterol can be used as a cell membrane structure, for steroid hormone synthesis, or finally converted into bile acids. Reverse cholesterol transport incorporates hdl metabolism and involves the movement of cholesterol from extrahepatic tissue, including the vessel wall, to the liver for excretion. The in vitro testing of the possibility that lcat plays a role in cholesterol transport was mainly hampered by the fact that most of the cholesterol of freshly prepared plasma lipoproteins is already esterified, that is, if the enzyme is able to alter the. After efflux to hdl, cholesterol may be esterified in the plasma by the enzyme lecithin. Continuous transport of a small fraction of plasma membrane. Pdf new insights into the regulation of hdl metabolism.
Reverse cholesterol transport is a multistep process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream. It has long been known that cellular cholesterol levels are. Reverse cholesterol transport rct is a term used to describe the efflux of excess cellular cholesterol from peripheral tissues and its return to the liver for. Cholesterol efflux and reverse cholesterol transport. When human hdl is run on a size exclusion column or nondenaturing gradient gels, it is evident that hdl is polydisperse with several discrete particle sizes evident. Chapter 16 lipid metabolism triacylglycerols tgs and glycogen are the two major forms of stored energy in vertebrates glycogen can supply atp for muscle contraction for less than an hour sustained work is fueled by metabolism of tgs which are very efficient energy stores because. The regulation of reverse cholesterol transport and cellular. Excess cholesterol and triglycerides can damage your blood vessels, leading to heart disease. Pdf chronic intermittent psychological stress promotes.
Reverse cholesterol transport and cholesterol efflux in. New insights into the regulation of hdl metabolism and reverse. Review pathophysiology of reverse cholesterol transport. The movement of cholesterol from extrahepatic tissues to the liver was termed reverse cholesterol transport by glomset. Abstract reverse cholesterol transport rct is a term used to describe the efflux of excess cellular cholesterol from pe ripheral tissues and its return to the liver.
This is the ratelimiting step of the rct pathway and requires the efflux of free cholesterol to cholesterol acceptors such as nascent or mature hdl highdensity lipoprotein along with macrophage egress from the. We have previouslydemonstrated in cultured hepatocytes that p2y. An important step in this reverse cholesteroltransport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipidpoor apolipoprotein ai particles designated pre beta hdl. Total cholesterol measured in your blood is only part of the story. The objective of this paper is an overview of making a few changes in diet.
Mark brown2 1saha 2 cardiovascular research center, university of kentucky, lexington, ky 405360509, usa. Pdf hdl receptors and reverse cholesterol transport. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the precursor for steroid hormones. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport rct. The transfer of cholesterol from macrophage foam cells to liver and feces the macrophagespecific reverse cholesterol. Cholesterol is of vital importance for the human body. Hdl and reverse cholesterol transport circulation research. Reverse cholesterol transport is a multistep process resulting in the net movement of. Hdl and reverse cholesterol transport biomarkers kayla a. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein ai. Pdf reverse cholesterol transport is the name justifiable. Hdl carries old cholesterol that has been discarded by cells back to the liver for recycling or excretion colpo, 2005. Rct from macrophages in atherosclerotic plaques macrophage rct is a critical mechanism of antiatherogenecity of highdensity lipoproteins hdl.
Reverse cholesterol transport rct reverse cholesterol transport is a mechanism by which the body removes excess cholesterol from peripheral tissues and delivers them to the liver, where it will be redistributed to other tissues or removed from the body by the gallbladder. A short guide to reverse cholesterol transport cholesterol is a molecule required by every cell of the body in fairly large amounts. Antagonism of mir33 in mice promotes reverse cholesterol transport and regression of atherosclerosis katey j. A short guide to reverse cholesterol transport the. Cholesterol from nonhepatic peripheral tissues is transferred to hdl by the abca1 atpbinding cassette transporter. How rafts contribute to cholesterol metabolism and transport in the cell is still an open issue.
Highdensity lipoprotein cholesterol as an independent risk factor in cardiovascular. If this is the ratelimiting step, then the flux of cholesterol through the entire reverse cholesterol transport pathway may be. Reverse cholesterol transport rct is the process of cholesterol movement from the extrahepatic tissues back to the liver. It can be easily synthesised by these cells, or taken up by them from ldl and other apob lipoproteins, but cannot be broken down. Consistent effects of genes involved in reverse cholesterol transport on plasma lipid and apolipoprotein levels in cardia participants. Cholesterol andlipoproteinmetabolism atherosclerosis. Recent advances suggest that cholesterol exerts many of its actions mainly by maintaining sphingolipid rafts in a functional state.
The importance of cholesterol in the body definition. Recent studies support changes to the widely cited reverse cholesterol transport rct mechanism. Cholesterol transport an overview sciencedirect topics. There are different types of cholesterol in our blood. Macneil4, zhihua jiang1 1department of animal sciences, washington state university, pullman, washington, united states of america. It is well established that cholesterol esterenriched foam cells are the hallmark of atherosclerotic plaques. Decreased reverse cholesterol transport from tangier disease fibroblasts. Reverse cholesterol transport rct is a process by which cholesterol in nonhepatic tissues is transported back to the liver via plasma components, such as hdl, along with atp binding cassette transporters, such as abca1 and abcg1 60. Reverse cholesterol transport rct is the process of cholesterol movement from the extrahepatic tissues back to the liver 7, 8.
Ultracentrifugation can separate 2 major density subfractions, hdl 2 density between 1. Pdf cholesterol efflux and reverse cholesterol transport. This is the ratelimiting step of the rct pathway and requires the efflux of free cholesterol to cholesterol acceptors such as nascent or mature hdl highdensity lipoprotein along with. Reverse cholesterol transport is a multistep process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the. The uptake of cholesterol from high density lipoproteins hdl by the liver is an important step in the hepatobiliary rct pathway. Elevated hdl cholesterol is functionally ineffective in. 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. Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The main lipoprotein involved in this process is the hdlc. Intravenous administration of apoaiphospholipid complexes should enhance the initial step in the reverse cholesterol transport pathway efflux of cholesterol to nascent hdl. Review article dynamics of reverse cholesterol transport.
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