Disappearance of two major phosphatidylcholines from plasma is predominantly via LCAT and hepatic lipase

Shamburek, R. D.; Zech, L. A.; Cooper, Patricia S.; VandenBroek, J M; Schwartz, Charles C.

doi:10.1152/ajpendo.1996.271.6.e1073

Cited by 11 publications

(11 citation statements)

References 27 publications

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“…For example, in rat, the plasma t 1/2 for the disappearance of [ 3 H]PC is ~1 h. This process is mediated, in part, by LCAT and hepatic lipase-mediated hydrolysis, which account for ≥90% of PC clearance. 61 In contrast to the nHDL-lipids, the plasma t 1/2 for nHDL-[ 125 I]apo AI is longer, 460 min, and after fusion with HDL and subsequent its release as lipid-free or poor, apo AI is available for additional efflux cycles.…”

Section: Discussionmentioning

confidence: 99%

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

Gillard

Gotto

et al. 2017

ATVB

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Objective Reverse cholesterol transport (RCT) comprises cholesterol efflux from ABCA1-expressing macrophages to apo AI giving nascent high density lipoprotein (nHDL), esterification of nHDL-free cholesterol (FC), selective hepatic extraction of HDL-lipids, and hepatic conversion of HDL-cholesterol to bile salts, which are excreted. We tested this model by identifying the fates of nHDL-[3H]FC, [14C]PL, and [125I]apo AI in serum in vitro and in vivo. Approach and Results During in vitro incubation of human serum, nHDL-[3H]FC and [14C]PL rapidly transfer to HDL and low density lipoproteins (LDL; t1/2 = 2–7 min) while nHDL-[125I]apo AI transfers solely to HDL (t1/2<10 min) and to the lipid-free form (t1/2 >480 min). Following injection into mice nHDL-[3H]FC and [14C]PL rapidly transfer to liver (t1/2 ~ 2–3 min) whereas apo AI clears with t1/2 = ~460 min. The plasma nHDL-[3H]FC esterification rate is slow (0.46%/h) compared to hepatic uptake. Phospholipid transfer protein enhances nHDL-[14C]PL but not nHDL-[3H]FC transfer to cultured Huh7 hepatocytes. Conclusions nHDL-FC, PL, and apo AI enter different pathways in vivo. Most nHDL-[3H]FC and [14C]PL are rapidly extracted by the liver via scavenger receptor class B member 1 and spontaneous transfer; hepatic PL uptake is promoted by phospholipid transfer protein. nHDL-[125I]apo AI transfers to HDL and to the lipid-free form that can be recycled to nHDL formation. Cholesterol esterification by LCAT is a minor process in nHDL metabolism. These findings could guide the design of therapies that better mobilize peripheral tissue-FC to hepatic disposal.

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Section: Discussionmentioning

confidence: 99%

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

Gillard

Gotto

et al. 2017

ATVB

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“…Our metabolic studies indicate rapid transfer/exchange of injected, radiolabeled HDL phospholipids and phospholipids in apoBcontaining lipoproteins in mice receiving rPLTP.AdV, confirming the results of previous in vitro experiments (2). We repeated those studies with radiolabeled PC ether, which in contrast to PC cannot be resecreted by the liver, to prove direct transfer/exchange from HDL to apoB-containing lipoproteins in plasma as opposed to an uptake/resecretion process of radiolabeled PC via the liver (45). In addition, increased delivery of HDL lipids to the liver in mice treated with rPLTP.AdV might be expected to modulate lipoprotein secretion by the liver.…”

Section: Of Recombinant Adenovirusmentioning

confidence: 99%

Plasma Phospholipid Transfer Protein

Föger

Santamarina-Fojo

Shamburek

et al. 1997

Journal of Biological Chemistry

129

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In vitro studies have shown that plasma phospholipid transfer protein (PLTP) converts isolated human high density lipoprotein-3 (HDL 3 ) into larger HDL particles and generates lipid-poor apoA-I containing nascent HDL. To evaluate the role of PLTP in vivo we generated recombinant adenovirus vectors containing either human PLTP cDNA (rPLTP.AdV) or the reporter luciferase cDNA as a control. After intravenous infusion of 4 ؋ 10 7 plaque-forming units (low dose) and 4 ؋ 10 8 plaqueforming units (high dose) of rPLTP.AdV into mice, PLTP activity in plasma increased from base-line levels of 8.4 ؎ 0.2 to 108 ؎ 17 and from 8.9 ؎ 0.6 to 352 ؎ 31 mol/ml/h, respectively, on day 4 (both p < 0.001). Thus, both low and high doses of rPLTP.AdV led to pronounced overexpression of human PLTP in mice. On day 4 after treatment, mice treated with low and high doses of rPLTP.AdV showed decreased HDL cholesterol (؊54% and ؊91%) and apoA-I (؊64% and ؊98%) (all p < 0.05). Kinetic studies revealed that the fractional catabolic rates of HDL labeled with The rate of spontaneous transfer of phospholipids between circulating lipoproteins in human plasma is too slow to allow for the rapid intravascular remodeling of lipoproteins (1, 2). Thus, two specialized glycoproteins, cholesteryl ester transfer protein (CETP) 1 and phospholipid transfer protein (PLTP), are secreted into the circulation to facilitate the transfer of surface phospholipids between high density lipoproteins (HDL) and other lipoproteins and, potentially, between cells and lipoproteins (3, 4). Of the two plasma lipid transfer proteins, only CETP is capable of additionally catalyzing the transfer of neutral core lipids between HDL and other lipoproteins, whereas PLTP is not (5-7). However, lipid transfers between HDL subfractions mediated by PLTP may be just as important as lipid transfers between HDL and other lipoproteins (8, 9). Presumably, PLTP-mediated phospholipid transfer between HDL particles (9) converts isolated human HDL 3 into a population of larger HDL particles with concomitant loss of apoA-I from the particles (9 -11). Thus, HDL remodeling mediated by PLTP may help to generate nascent HDL particles, which are considered crucial for the removal of cholesterol from cells (12), the first step in reverse cholesterol transport.In the last 2 years, our understanding of the structure of PLTP has advanced considerably (13). The human PLTP gene contains 16 exons, spanning approximately 13 kilobase pairs on the long arm of chromosome 20 (14, 15). The cDNA is 1750 base pairs long and encodes a 17-amino acid signal peptide and a 476-amino acid mature protein (16). The molecular mass observed upon SDS-polyacrylamide gel electrophoresis of PLTP purified from human plasma is approximately 81 kDa (13), considerably higher than the protein mass predicted from the cDNA, i.e. 55 kDa (16), a difference presumably due to glycosylation. The cDNA of PLTP shows sequence homology to lipopolysaccharide-binding protein, bactericidal permeability-increasing protein, and CETP, which places P...

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“…28 However, as explained earlier, these antioxidative activities are compromised in several clinical conditions. Lipolysis of glycerophospholipids by phospholipases such as endothelial lipase and secretory phospholipase A2, 233,234 which are activated by inflammation as well as the LCAT action, 235 generate lysophospholipids that in turn are bioactive and can exert pro-inflammatory activities. [233][234][235][236][237] Changes in the glycerophospholipid composition may hence affect the functionality of HDLs and serve as a biomarker.…”

Section: Post-translational Modifications Of Proteinsmentioning

confidence: 99%

“…Lipolysis of glycerophospholipids by phospholipases such as endothelial lipase and secretory phospholipase A2, 233,234 which are activated by inflammation as well as the LCAT action, 235 generate lysophospholipids that in turn are bioactive and can exert pro-inflammatory activities. [233][234][235][236][237] Changes in the glycerophospholipid composition may hence affect the functionality of HDLs and serve as a biomarker. As yet, however, no data from clinical studies are available that show associations and correlations of phospholipid composition with disease and functionality of HDLs, respectively.…”

Section: Post-translational Modifications Of Proteinsmentioning

confidence: 99%

High-Density Lipoproteins

Annema

Eckardstein

2013

Circ J

143

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk. 2433Multifunctional but Vulnerable HDL munication of results. 15 As yet, clinical and epidemiological studies have come to discrepant and inconsistent conclusions on the prognostic performance of HDL subclasses differentiated by size. 14,20-24 Sometimes the associations of cardiovascular risk with the various HDL subclass concentrations were not stronger than with HDL-C, 20,21 and even if so, the associations with size were discrepant: significant associations with risk of cardiovascular events or stroke were found for small HDL in some studies, 22,23 but for medium-sized HDL 21,23 or large HDL 14,20,21,24 in others.Previous proteomic, lipidomic, and transcriptomic studies revealed a much greater structural complexity of HDLs: 80 different proteins, 25,26 more than 200 lipid species, 27,28 and several microRNAs 29,30 have been identified in HDL isolated from plasma by either ultracentrifugation, gel filtration, or immunoaffinity chromatography (Figure 1). Among the proteins, apoA-II is present in HDLs at the highest concentration after that of apoA-I and has been investigated for its cardiovascular risk association by several studies. In contrast to initial findings, large prospective studies did not find any significant differences in the risk association between apoA-II-containing and apoA-II-free HDL. [15][16][17] Despite their much lower concentrations relative to the 2 major proteins apoA-I and apoA-II and relative to the major lipids, many quantitatively minor componen...

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Disappearance of two major phosphatidylcholines from plasma is predominantly via LCAT and hepatic lipase

Cited by 11 publications

References 27 publications

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

ABCA1-Derived Nascent High-Density Lipoprotein–Apolipoprotein AI and Lipids Metabolically Segregate

Plasma Phospholipid Transfer Protein

High-Density Lipoproteins

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