apoE3[K146N/R147W] acts as a dominant negative apoE form that prevents remnant clearance and inhibits the biogenesis of HDL

Abstract

apoE is a very important component of the lipoprotein transport system that has a dual functionality. It is essential for the clearance of lipoprotein remnants from the circulation ( 1, 2 ) and also promotes the biogenesis of apoEcontaining HDL ( 3 ). As a result of this and possibly other unidentifi ed functions, apoE plays a central role in atheroprotection ( 4-6 ).Lipoprotein-bound apoE is a ligand for the LDL receptor ( 7,8 ), as well as other receptors in vitro ( 9-11 ). In vivo and in vitro studies have shown that mutations in apoE that diminish binding of apoE-containing lipoproteins to the LDL receptor are associated with high plasma cholesterol levels and cause premature atherosclerosis in humans and experimental animals ( 4-6, 12 ).In addition to its functions in remnant clearance and the biogenesis of HDL, lipid-free or lipoprotein-associated apoE has been reported to affect various other biological processes through signal transduction mechanisms ( 13-21 ). apoE promotes ABCA1-and Scavenger receptor class B type I-mediated cholesterol effl ux ( 22, 23 ) and has antioxidant and anti-infl ammatory properties ( 14,15,20,(24)(25)(26)(27). apoE also suppresses smooth muscle cell migration and proliferation by interactions with low density lipoprotein Abstract The K146N/R147W substitutions in apoE3 were described in patients with a dominant form of type III hyperlipoproteinemia. The effects of these mutations on the in vivo functions of apoE were studied by adenovirus- Abbreviations: ANS, 8-anilinonaphthalene-1-sulfonic acid; apoA-I Ϫ / Ϫ , apoA-I-defi cient; apoE Ϫ / Ϫ , apoE-defi cient; CE, cholesteryl ester; EM, electron microscopy; FPLC, fast protein liquid chromatography; HLP, hyperlipoproteinemia; HSPG, heparan sulfate proteoglycan; pfu, plaque forming unit; TC, total cholesterol .

Beneficial effect of lycopene on anti-diabetic nephropathy through diminishing inflammatory response and oxidative stress

“…20 Growing studies have reported that high-density lipoprotein (HDL), the smallest lipoprotein particle, tends to have fewer risks of developing cardiovascular and diabetic diseases. 21 In contrast, the low-density lipoprotein (LDL) particle is classified as bad cholesterol that can transport the lipid molecules into artery walls and attract macrophages, thereby forming atherosclerosis or inducing diabetes. 22 Therefore, lipoprotein-lowering strategy is used to inhibit the development of diabetes-related comorbidities, including DN.…”

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review

“…Treatment options for these individuals are limited. A recent study shows that type III hyperlipoproteinemia is induced by mutations in the LDL receptor binding domain of apoE and is characterized by inhibition of both remnant lipoprotein clearance and HDL biogenesis ( 154 ). apoE mimetic peptide therapy may be ideally suited for treatment of hypercholesterolemia associated with defects in LDL receptor function.…”