| http://purl.uniprot.org/citations/31996466 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31996466 | http://www.w3.org/2000/01/rdf-schema#comment | "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 apoC-II on the Anton 2 supercomputer, structural prediction programs, and biophysical techniques. Efficacy of D6PV was assessed ex vivo in human HTG plasma and was found to be more potent than full-length apoC-II in activating LPL. D6PV markedly lowered TG by more than 80% within a few hours in both apoC-II-deficient mice and hAPOC3-transgenic (Tg) mice. In hAPOC3-Tg mice, D6PV treatment reduced plasma apoC-III by 80% and apoB by 65%. Furthermore, low-density lipoprotein (LDL) cholesterol did not accumulate but rather was decreased by 10% when hAPOC3-Tg mice lacking the LDL-receptor (hAPOC3-Tg × Ldlr-/- ) were treated with the peptide. D6PV lowered TG by 50% in whole-body inducible Lpl knockout (iLpl-/- ) mice, confirming that it can also act independently of LPL. D6PV displayed good subcutaneous bioavailability of about 80% in nonhuman primates. Because it binds to high-density lipoproteins, which serve as a long-term reservoir, it also has an extended terminal half-life (42 to 50 hours) in nonhuman primates. In summary, D6PV decreases plasma TG by acting as a dual apoC-II mimetic and apoC-III antagonist, thereby demonstrating its potential as a treatment for HTG."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.org/dc/terms/identifier | "doi:10.1126/scitranslmed.aaw7905"xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Pryor M."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Tang J."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Basu D."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Wu M.J."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Freeman L.A."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Remaley A.T."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Wilson S."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Ghosh S.S."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Amar M."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Goldberg I.J."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Neher S.B."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Davidson M."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Pastor R.W."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Kakkar R."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Lo L."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Cougnoux A."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Drake S.K."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Wolska A."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Pourmousa M."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Devalaraja M."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/author | "Sviridov D.O."xsd:string |
| http://purl.uniprot.org/citations/31996466 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |