2020
DOI: 10.1126/scitranslmed.aaw7905
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A dual apolipoprotein C-II mimetic–apolipoprotein C-III antagonist peptide lowers plasma triglycerides

Abstract: Recent genetic studies have established that hypertriglyceridemia (HTG) is causally related to cardiovascular disease, making it an active area for drug development. We describe a strategy for lowering triglycerides (TGs) with an apolipoprotein C-II (apoC-II) mimetic peptide called D6PV that activates lipoprotein lipase (LPL), the main plasma TG-hydrolyzing enzyme, and antagonizes the TG-raising effect of apoC-III. The design of D6PV was motivated by a combination of all-atom molecular dynamics simulation of a… Show more

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Cited by 60 publications
(57 citation statements)
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“…Another novel strategy to lower plasma triglycerides was recently reported by Wolska et al (146). They developed a dual apoC-II mimetic and apoC-III antagonist (called D6PV) that activates LPL.…”
Section: Pharmacological Interventions For Reducing Plasma Apoc-iii Lmentioning
confidence: 99%
“…Another novel strategy to lower plasma triglycerides was recently reported by Wolska et al (146). They developed a dual apoC-II mimetic and apoC-III antagonist (called D6PV) that activates LPL.…”
Section: Pharmacological Interventions For Reducing Plasma Apoc-iii Lmentioning
confidence: 99%
“…This peptide shows some LPL-independent TG lowering activity, probably because it has dual APOC2 and APOC3 antagonistic effects, as it partially decreases plasma TG in whole-body inducible Lpl −/− mice. It also lowers TG levels in non-human primates (181). Its effect on atherosclerosis in animal models (and humans) is so far unknown.…”
Section: Apoc2 Mimetic Peptidementioning
confidence: 99%
“…These short peptides are directly derived from the sequence of apolipoproteins (apo) or have another amino acid sequence that mimics their conformation of amphipathic helices [ 9 ]. Most studies have analyzed the effects of peptides derived from apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE) [ 10 , 11 ], although other apolipoprotein mimetic peptides, such as apolipoprotein C-II (apoC-II) [ 12 ] or apolipoprotein J (apoJ) [ 13 ], have also been used. The main mechanisms of action of apoA-I and apoE mimetics are theoretically different, since apoE mimetics mediate hepatic clearance of atherogenic apoB-containing lipoproteins from the circulation via interaction with lipoprotein receptors, whereas apoA-I mimetics mainly stimulate the reverse cholesterol transport pathway [ 11 ].…”
Section: Introductionmentioning
confidence: 99%