Biomaterial Database

Apolipoprotein A-I mimetic peptide 4F blocks sphingomyelinase-induced LDL aggregation. 2015

Su Duy Nguyen, and Matti Javanainen, and Sami Rissanen, and Hongxia Zhao, and Jenni Huusko, and Annukka M Kivelä, and Seppo Ylä-Herttuala, and Mohamad Navab, and Alan M Fogelman, and Ilpo Vattulainen, and Petri T Kovanen, and Katariina Öörni

Wihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland.

Lipolytic modification of LDL particles by SMase generates LDL aggregates with a strong affinity for human arterial proteoglycans and may so enhance LDL retention in the arterial wall. Here, we evaluated the effects of apoA-I mimetic peptide 4F on structural and functional properties of the SMase-modified LDL particles. LDL particles with and without 4F were incubated with SMase, after which their aggregation, structure, and proteoglycan binding were analyzed. At a molar ratio of L-4F to apoB-100 of 2.5 to 20:1, 4F dose-dependently inhibited SMase-induced LDL aggregation. At a molar ratio of 20:1, SMase-induced aggregation was fully blocked. Binding of 4F to LDL particles inhibited SMase-induced hydrolysis of LDL by 10% and prevented SMase-induced LDL aggregation. In addition, the binding of the SMase-modified LDL particles to human aortic proteoglycans was dose-dependently inhibited by pretreating LDL with 4F. The 4F stabilized apoB-100 conformation and inhibited SMase-induced conformational changes of apoB-100. Molecular dynamic simulations showed that upon binding to protein-free LDL surface, 4F locally alters membrane order and fluidity and induces structural changes to the lipid layer. Collectively, 4F stabilizes LDL particles by preventing the SMase-induced conformational changes in apoB-100 and so blocks SMase-induced LDL aggregation and the resulting increase in LDL retention.

UI	MeSH Term	Description	Entries
D008066	Lipolysis	The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.	Lipolyses
D008077	Lipoproteins, LDL	A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.	Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001011	Aorta	The main trunk of the systemic arteries.	Aortas
D013108	Sphingomyelin Phosphodiesterase	An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.	Sphingomyelin Cholinephosphohydrolase,Sphingomyelin Cleaving Enzyme,Sphingomyelinase,Sphingomyelinase C
D016632	Apolipoprotein A-I	The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.	Apo A-I,Apo A-1,Apo A-I Isoproteins,Apo A1,Apo AI,ApoA-1,ApoA-I,Apolipoprotein A-1,Apolipoprotein A-I Isoprotein-2,Apolipoprotein A-I Isoprotein-4,Apolipoprotein A-I Isoproteins,Apolipoprotein A1,Apolipoprotein AI,Apolipoprotein AI Propeptide,Pro-Apo A-I,Pro-Apolipoprotein A-I,Proapolipoprotein AI,Apo A I Isoproteins,Apolipoprotein A 1,Apolipoprotein A I,Apolipoprotein A I Isoprotein 2,Apolipoprotein A I Isoprotein 4,Apolipoprotein A I Isoproteins,Pro Apo A I,Pro Apolipoprotein A I
D053299	Apolipoprotein B-100	A 513-kDa protein synthesized in the LIVER. It serves as the major structural protein of low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). It is the ligand for the LDL receptor (RECEPTORS, LDL) that promotes cellular binding and internalization of LDL particles.	Apo B-100,Apo-B-100,ApoB-100,Apo B 100,ApoB 100,Apolipoprotein B 100
D032701	Biomimetics	An interdisciplinary field in materials science, ENGINEERING, and BIOLOGY, studying the use of biological principles for synthesis or fabrication of BIOMIMETIC MATERIALS.	Mimetics, Biological,Bio-inspired Engineering,Biomimicry Engineering,Biomimicry Science,Bio inspired Engineering,Bio-inspired Engineerings,Biological Mimetic,Biological Mimetics,Biomimetic,Biomimicry Engineerings,Biomimicry Sciences,Engineering, Bio-inspired,Engineering, Biomimicry,Engineerings, Bio-inspired,Engineerings, Biomimicry,Mimetic, Biological,Science, Biomimicry,Sciences, Biomimicry