Analytical Biochemistry p. 41 - 50 (2019)
Update date:2022-08-11
Topics:
Onorato, Joelle M.
Xu, Carrie
Chen, Xue-Qing
Rose, Anne V.
Generaux, Claudia
Lentz, Kimberley
Shipkova, Petia
Arthur, Susan
Hennan, James K.
Haskell, Roy
Myers, Michael C.
Lawrence, R. Michael
Finlay, Heather J.
Basso, Michael
Bostwick, Jeffrey
Fernando, Gayani
Garcia, Ricardo
Hellings, Samuel
Hsu, Mei-Yin
Zhang, Rongan
Zhao, Lei
Gargalovic, Peter
Apelin, the endogenous ligand for the APJ receptor, has generated interest due to its beneficial effects on the cardiovascular system. Synthesized as a 77 amino acid preproprotein, apelin is post-translationally cleaved to a series of shorter peptides. Though (Pyr)1apelin-13 represents the major circulating form in plasma, it is highly susceptible to proteolytic degradation and has an extremely short half-life, making it challenging to quantify. Literature reports of apelin levels in rodents have historically been determined with commercial ELISA kits which suffer from a lack of selectivity, recognizing a range of active and inactive isoforms of apelin peptide. (Pyr)1apelin-13 has demonstrated beneficial hemodynamic effects in humans, and we wished to evaluate if similar effects could be measured in pre-clinical models. Despite development of a highly selective LC/MS/MS method, in rodent studies where (Pyr)1apelin-13 was administered exogenously the peptide was not detectable until a detailed stabilization protocol was implemented during blood collection. Further, the inherent high clearance of (Pyr)1apelin-13 required an extended release delivery system to enable chronic dosing. The ability to deliver sustained doses and stabilize (Pyr)1apelin-13 in plasma allowed us to demonstrate for the first time the link between systemic concentration of apelin and its pharmacological effects in animal models.
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