Reverse cholesterol transport is the transport of cholesterol from the tissues back to liver/VLDL. My question is why do the tissues have this extra cholesterol in the first place (which they happen to return)?
Why would the cell synthesise extra cholesterol when excellent feedback mechanisms exist - eg. SREBP-SCAP-INSIG pathway to name one?
Does this happen only in the case of an atheromatous plaque or anywhere else too?
It is exactly true cells are tightly regulating their cholesterol. Part of this mechanism of cellular cholesterol control is the cholesterol efflux pathway where the trans-membrane protein ABCA1 is a key component. This pathway is under the control of cellular cholesterol (LXR). The extracellular acceptor of ABCA1 -cholesterol is apoA1 which is the main protein of High density lipoprotein (HDL). This would be the first step of reverse cholesterol at the cellular level.
Thanks! So does this mean that the cholesterol efflux is one way of regulating the cells cholesterol? So ultimately, it is one (of many) reason why cell regulates the cholesterol efficiently.
Under pathophysiological conditions monocytes will invade into the subendothelial space of early atherosclerotic lesions, transform to macrophages, take up lipoproteins and other cholsterol containing material and send the cholesterol back to the liver by means of Apo A1 and HDL respectively. However, the "good guy" will turn into a "bad guy" when LDL deposited there will be oxidised and become cytotoxic because of an increasing amount of oxidised cholesterol. Thus, the cells will die and the formation of the lesions will progress.
Best regards,
Günther
yes while in atherosclerosis plaque progression but also at normal physiological state
Following points may plz be considered in this regard
1. Most of the tissues need cholesterol at least for integrity of their membrane.
2. Most of these tissues can synthesize their own cholesterol which is in accordance to the demand.
3. Tissues also acquire cholesterol from LDL which is not that regulated (CE stores are there even after intake regulation by LDL receptor downregulation, stopping cholesterol synthesis by inhibiting HMG CoA reductase).
4. Now what to do with extra cholesterol if any?
5. Tissues store cholesterol but can not metabolize it.
6. when HSL is active in adipose or in other situations in tissues other than adipose , cholesterol is released just like glycerol and HDL takes it up and delivers back to liver while glycerol can travel as free molecule to liver to participate in gluconeogensis.
7. This mechanism does not fully explain the metabolism and further investigation is needed.
Best Regards
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