scholarly journals Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Xiuting Xu ◽  
Zikai Song ◽  
Bao Mao ◽  
Guoliang Xu
Keyword(s):  
Reverse Cholesterol Transport ◽  
Scavenger Receptor ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
The Body ◽  
Apolipoprotein A1 ◽  
Cholesterol Transport ◽  
Class B

Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.

Quercetin induces the selective uptake of HDL-cholesterol via promoting SR-BI expression and the activation of the PPARγ/LXRα pathway

2018 ◽  
Vol 9 (1) ◽  
pp. 624-635 ◽  
Author(s):  
Kun Ren ◽  
Ting Jiang ◽  
Guo-Jun Zhao
Keyword(s):  
Reverse Cholesterol Transport ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Transport ◽  
Type I ◽  
Lipid Uptake ◽  
Scavenger Receptor Class ◽  
Class B ◽  
Selective Lipid Uptake

Reverse cholesterol transport (RCT) is the process to deliver cholesterol to the liver for further excretion and involves scavenger receptor class B type I (SR-BI)-mediated selective lipid uptake (SLU) from high-density lipoprotein cholesterol (HDL-C).

scholarly journals MEDI6012: Recombinant Human Lecithin Cholesterol Acyltransferase, High‐Density Lipoprotein, and Low‐Density Lipoprotein Receptor–Mediated Reverse Cholesterol Transport

2021 ◽  
Author(s):  
Richard T. George ◽  
Liron Abuhatzira ◽  
Susan M. Stoughton ◽  
Sotirios K. Karathanasis ◽  
Dewei She ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
High Density Lipoprotein Cholesterol ◽  
Reverse Cholesterol Transport ◽  
Low Density Lipoprotein ◽  
Cholesterol Acyltransferase ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesterol Transport ◽  
Low Density ◽  
Lecithin Cholesterol Acyltransferase

Background MEDI6012 is recombinant human lecithin cholesterol acyltransferase, the rate‐limiting enzyme in reverse cholesterol transport. Infusions of lecithin cholesterol acyltransferase have the potential to enhance reverse cholesterol transport and benefit patients with coronary heart disease. The purpose of this study was to test the safety, pharmacokinetic, and pharmacodynamic profile of MEDI6012. Methods and Results This phase 2a double‐blind study randomized 48 subjects with stable coronary heart disease on a statin to a single dose of MEDI6012 or placebo (6:2) (NCT02601560) with ascending doses administered intravenously (24, 80, 240, and 800 mg) and subcutaneously (80 and 600 mg). MEDI6012 demonstrated rates of treatment‐emergent adverse events that were similar to those of placebo. Dose‐dependent increases in high‐density lipoprotein cholesterol were observed with area under the concentration‐time curves from 0 to 96 hours of 728, 1640, 3035, and 5318 should be: mg·h/mL in the intravenous dose groups and 422 and 2845 mg·h/mL in the subcutaneous dose groups. Peak mean high‐density lipoprotein cholesterol percent change was 31.4%, 71.4%, 125%, and 177.8% in the intravenous dose groups and 18.3% and 111.2% in the subcutaneous dose groups, and was accompanied by increases in endogenous apoA1 (apolipoprotein A1) and non‐ATP‐binding cassette transporter A1 cholesterol efflux capacity. Decreases in apoB (apolipoprotein B) were observed across all dose levels and decreases in atherogenic small low‐density lipoprotein particles by 41%, 88%, and 79% at the 80‐, 240‐, and 800‐mg IV doses, respectively. Conclusions MEDI6012 demonstrated an acceptable safety profile and increased high‐density lipoprotein cholesterol, endogenous apoA1, and non‐ATP‐binding cassette transporter A1 cholesterol efflux capacity while reducing the number of atherogenic low‐density lipoprotein particles. These findings are supportive of enhanced reverse cholesterol transport and a functional high‐density lipoprotein phenotype. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02601560.

scholarly journals Treatment with apolipoprotein A1 protects mice against doxorubicin-induced cardiotoxicity in a scavenger receptor class B, type I-dependent manner

2019 ◽  
Vol 316 (6) ◽  
pp. H1447-H1457 ◽  
Author(s):  
Kristina K. Durham ◽  
George Kluck ◽  
Kei Cheng Mak ◽  
Yak D. Deng ◽  
Bernardo L. Trigatti
Keyword(s):  
High Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
High Density ◽  
Cardiomyocyte Apoptosis ◽  
Apolipoprotein A1 ◽  
Type I ◽  
Dependent Manner ◽  
Scavenger Receptor Class ◽  
Class B

Doxorubicin, an agent used to treat a variety of cancers, is cardiotoxic by triggering cardiomyocyte apoptosis. We previously showed that treating cultured cardiomyocytes with human high-density lipoprotein in vitro or transgenic overexpression of human apolipoprotein A1, its main structural protein, protects against doxorubicin-induced cardiomyocyte apoptosis in a manner dependent on the scavenger receptor class B type I [Durham KK, Chathely KM, Mak KC, Momen A, Thomas CT, Zhao YY, MacDonald ME, Curtis JM, Husain M, Trigatti BL. HDL protects against doxorubicin-induced cardiotoxicity in a scavenger receptor class B type 1-, phosphatidylinositol 3-kinase-, and Akt-dependent manner. Am J Physiol Heart Circ Physiol 314: H31–H44, 2018]. This was due to high-density lipoprotein-induced activation of Akt signaling in cardiomyocytes. We now demonstrate that mice lacking the scavenger receptor class B, type I exhibit increased sensitivity to doxorubicin-induced cardiomyocyte apoptosis in vivo. Cardiomyocytes expressing scavenger receptor class B, type I are protected from doxorubicin-induced apoptosis by preincubation with high-density lipoprotein isolated from wild-type mice, whereas high-density lipoprotein from scavenger receptor class B, type 1 knockout mice is less effective. Cardiomyocytes from scavenger receptor class B, type I knockout mice, however, are not protected by high-density lipoprotein in vitro, and hearts from knockout mice are more sensitive to doxorubicin in vivo. Pharmacological administration of purified apolipoprotein A1 dramatically protected wild-type mice from doxorubicin-induced cardiotoxicity and left ventricular dysfunction, whereas this protection was lost in scavenger receptor class B, type I-deficient mice. This demonstrates, at least in mice, that high-density lipoprotein therapy can confer protection against doxorubicin-induced cardiomyocyte apoptosis in a manner mediated by the scavenger receptor class B, type I. NEW & NOTEWORTHY We show that scavenger receptor class B, type I (SR-B1) mediates HDL-dependent protection against doxorubicin-induced cardiomyocyte apoptosis and that this is a property of SR-B1 in cardiomyocytes in vitro and in hearts in vivo. We also demonstrate that pharmacological treatment with apolipoprotein A1, the major HDL structural protein, protects mice against doxorubicin-induced cardiomyocyte apoptosis and left ventricular dysfunction in an SR-B1-dependent manner. This suggests that HDL-targeted pharmacological therapy may hold promise for protecting against the deleterious, cardiotoxic side effects of this commonly used chemotherapeutic drug.

scholarly journals Apoprotein E and Reverse Cholesterol Transport

2018 ◽  
Vol 19 (11) ◽  
pp. 3479 ◽  
Author(s):  
Godfrey Getz ◽  
Catherine Reardon
Keyword(s):  
Reverse Cholesterol Transport ◽  
Cholesterol Efflux ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
The Body ◽  
Cholesterol Transport ◽  
Cellular Cholesterol ◽  
Multifunctional Protein ◽  
Apoprotein E

Apoprotein E (apoE) is a multifunctional protein. Its best-characterized function is as a ligand for low-density lipoprotein (LDL) receptor family members to mediate the clearance of apoB-containing atherogenic lipoproteins. Among its other functions, apoE is involved in cholesterol efflux, especially from cholesterol-loaded macrophage foam cells and other atherosclerosis-relevant cells, and in reverse cholesterol transport. 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. This process is thought to have a role in the attenuation of atherosclerosis. This review summarizes studies on the role of apoE in cellular cholesterol efflux and reverse cholesterol transport and discusses the identification of apoE mimetic peptides that may promote these pathways.

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