PCSK9 inhibition with alirocumab reduces lipoprotein(a) levels in nonhuman primates by lowering apolipoprotein(a) production rate

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Croyal, Mikael | Tran, Thi-Thu-Trang | Blanchard, Rose hélène | Le Bail, Jean-Christophe | Villard, Elise f. | Poirier, Bruno | Aguesse, Audrey | Billon-Crossouard, Stéphanie | Ramin-Mangata, Stéphane | Blanchard, Valentin | Nativel, Brice | Chemello, Kévin | Khantalin, Ilya | Thédrez, Aurélie | Janiak, Philip | Krempf, Michel | Boixel, Christophe | Lambert, Gilles | Guillot, Etienne

Edité par CCSD ; Portland Press -

International audience. Leucine was assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Kinetic parameters were calculated using numerical models with the SAAMII software. Compared with IgG1, alirocumab significantly reduced total cholesterol (TC) (-28%), LDL-C (-67%), Lp(a) (-56%), apolipoprotein B100 (apoB100) (-53%), and apo(a) (-53%). Alirocumab significantly increased the fractional catabolic rate of apoB100 (+29%) but not that of apo(a). Conversely, alirocumab sharply and significantly reduced the production rate (PR) of apo(a) (-42%), but not significantly that of apoB100, compared with IgG1, respectively.In line with the observations made in human hepatocytes, the present kinetic study establishes that PCSK9 neutralization with alirocumab efficiently reduces circulating apoB100 and apo(a) levels by distinct mechanisms: apoB primarily by enhancing its catabolism and apo(a) primarily by lowering its production.

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