HDL receptors

Krieger, M, 2001. Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest 108, 793-797. 

M. Krieger, T. Kirchhausen, Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI. Proc. Natl. Acad. Sci. USA 2002, 99, 15422-15427. 

The cholesterol esters of HDLs can also be transferred to VLDLs and LDLs through the action of the HDL-associated enzyme, cholesterol ester transfer protein (CETP). This has the added effect of allowing the excess cellular cholesterol to be returned to the liver through the LDL-receptor pathway as well as the HDL-receptor pathway. 

HDL, like LDL, is a cholesterol-rich particle, and is distinct from the other lipoprotein classes in that it does not contain apoB. HDL levels are inversely correlated with risk for atherosclerosis (Wilson et al., 1988). Nascent HDL particles are produced by direct synthesis (Hamilton, 1984), and excess surface remnants from chylomicrons and VLDL produced during the action of lipoprotein lipase (as noted above) enter the HDL density class. HDL appears to be involved in delivery of cholesterol to steroidogenic tissues as well as the removal of excess cholesterol from peripheral tissues and excretion from the system. This HDL-mediated removal of cholesterol has been termed reverse cholesterol transport (Glomset, 1968). Although apolipoproteins present in HDLs are cleared by the liver, the reverse cholesterol transport pathway has never been directly demonstrated. HDL can remove cholesterol from tissues, a process that may be partially mediated by interaction with a putative HDL receptor, with apoA-I as the ligand for that receptor (Oram el ai, 1983). The existence of an HDL receptor remains controversial saturable HDL binding may not be mediated by a specific apolipoprotein ligand and may not even be required for transfer of cholesterol from cells to... 

HDL (Johnson et ai, 1988 Slotte et al., 1987). However, binding of HDL to the putative HDL receptor may induce movement of cholesterol from intracellular pools to the cell surface, where it is available for transfer to HDL (Slotte et ai, 1987). 

Figure 26-21 Reverse cholesterol transport pathway. HDl High-density lipoproteins LDL, low-density lipoproteins tDL, intermediate-density lipoproteins HTL, hepatic lipoprotein lipase LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein apo E, apoiipoprotein E. Cholesterol is removed from macrophages and other arterial wall cells by an HDL-mediated process. The LCAT esterifies the cholesterol content of HDL to prevent it from reentering the ceils. Cholesterol esters are delivered to the liver by one of three pathways ( ) cholesterol esters are transferred from HDL to LDL by CETP and enter the liver through the specific LDL receptor pathway (2) cholesterol esters are selectively taken from HDL by HDL receptors and HDL particles are returned to circulation for further transport or (3) HDL have accumulated apo E and therefore the particles can enter the liver through remnant receptors, (From Gwynne JT. High density lipoprotein cholesterol levels as a marker of reverse cho/estero/ tronsport./ m j Cardiol I989 64 10G-I7G. Copyright 1989, with permission from Excerpta Medico Inc.)...

A-l Chylomicrons, HDL 120 28 Cofactor with LCAT, structural protein on HDL, ligand for HDL receptor Liver, intestine... 

Amp B results in mesangial cell contraction in vitro. This effect was related to a Ca + entry from the extracellular space via calcium channels [218]. In LLC-PKj and renal medullary interstitial cells AmB, in therapeutic doses, induced apoptosis, which could be prevented by recombinant human insuhn-like-growth-fac-tor-1 (IGF-1). Similar results were observed in rats [219]. In a mechanistic study it could be shown that Amp B bound to high-density lipoprotein (HDL) was less toxic to LLC-PKj cells than AmB alone or AmB bound to low-density lipoprotein (LDL). This result was thought to be related to the absence of HDL receptors in LLC-PKj cells [220,221]. The antifungal activity of AmB was not altered when associated to HDL or LDL. These results are of relevance for therapeutic applications [220]. 

Azhar, S., Nomoto, A., Leers-Sucheta, S., and Reaven, E. (1998). Simultaneous induction of an HDL receptor protein (SR-BI) and the selective uptake of HDL-cholesteryl esters in a physiologically relevant steroidogenic cell model. J Lipid Res 39, 1616-1628. 

Part of the CE formed in HDL is transferred to apo B lipoproteins, particularly VLDL and LDL, by a CE transfer protein (CETP), prior to removal of these lipoproteins by the liver. Another part of the CE in HDL is selectively internalized by the liver and by tissues synthesizing steroid hormones, by a scavenger receptor protein (SR-BI) (Chapter 20). Finally some CE is internalized as part of intact HDL by hepatic HDL receptors/binding proteins. 

Putative HDL receptors have been proposed in a variety of organs, including kidneys [20] and liver [21-23]. Table 3 shows that the specific binding of rat HDL to kidney membranes is not dependent on the Apo E content of HDL. 

HDL Receptor of Cultured Adipocytes and Its Role in Reverse Cholesterol Transport... 

I and LPA-I A-II particles are indeed competitors of labeled HDL3 for the binding to HDL receptor sites at the cell surface, excluding the lack of recognition of LP-A-I A-... 

Diseases that enhance LDL oxidation include diabetes and hypertriglyceridemia (115). Hyperglycemia increases LDL oxidation, in part, through an increase in glycation products, which subsequently enhances free radical production in stimulated inflammatory cells (115). Insulin and IGF-I cause an upregulation of LDL receptor and down regulation of HDL receptor (281). Insulin increases uptake and esterification of... 

---