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The proprotein convertases family is involved in several physiological processes such as cell growth, migration, and angiogenesis, and also in different pathological conditions. Evolocumab, an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), has recently been approved for treatment of hypercholesterolemia. This study aimed to investigate the effect of evolocumab on angiogenesis in human umbilical vein endothelial cells (HUVECs). Cell proliferation and migration were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell methods. In vitro angiogenesis was assessed by tube formation assay. Vascular endothelial growth factor (VEGF) secretion by HUVECs was also determined using an enzyme-linked immunosorbent assay kit. Evolocumab significantly increased HUVECs viability at 100[micro]g/mL. Significant enhancement in cell migration, and mean tubules length and size was observed at the concentrations of 10 and 100[micro]g/mL and also in mean number of junctions at the concentration of 100[micro]g/mL. Administration of evolocumab at the concentration of 10[micro]g/mL increased VEGF release into supernatants of HUVECs. Findings of this investigation provided in vitro evidence for pro-angiogenic activity of evolocumab through promoting cell proliferation, migration, tubulogenesis, and VEGF secretion in HUVECs. Key words: angiogenesis, cell proliferation, cell migration, HUVEC, PCSK9, evolocumab, VEGF. La famille des proproteine convertases joue un role dans plusieurs processus physiologiques comme la croissance cellulaire, la migration cellulaire et l'angiogenese, ainsi que dans differents etats pathologiques. L'evolocumab, un inhibiteur de la proproteine convertase subtilisine/kexine de type 9 (PCSK9), a recemment ete approuve dans le traitement de l'hypercholesterolemie. Ces travaux visaient a etudier l'effet de l'evolocumab sur l'angiogenese dans les cellules endotheliales des veines ombilicales chez l'humain (HUVEC). Nous avons evalue la proliferation et la migration cellulaires a l'aide des methodes dubromure de (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium et de Transwell. Nous avons evalue l'angiogenese in vitro a l'aide de l'epreuve de formation de tubes. Nous avons aussi evalue la secretion du VEGF (pour << vascular endothelial growth factor>>) par les cellules HUVEC a l'aide d'un kit d'ELISA (pour<< enzyme-linked immunosorbent assay>>). L'evolocumab a 100[micro]g/mL permettait d'augmenter la vitalite des cellules HUVEC de facon marquee. Nous avons observe une nette augmentation de la migration des cellules et des longueurs et des tailles moyennes des tubules a des concentrations de 10 et de 100[micro]g/mL, avec une augmentation du nombre moyen de jonctions a la concentration de 100[micro]g/mL. A la concentration de 10[micro]g/mL, l'administration d'evolocumab entrainait une augmentation de la liberation de VEGF dans le liquide surnageant les cellules HUVEC. Les resultats de cette etude ont permis d'obtenir des donnees in vitro temoignant de l'activite proangiogenique de l'evolocumab par l'intermediaire de l'augmentation de la proliferation, de la migration, de la tubulogenese et de la secretion de VEGF avec les cellules HUVEC. [Traduit par la Redaction] Mots-cles: angiogenese, proliferation cellulaire, migration cellulaire, HUVEC, PCSK9, evolocumab, VEGF., Introduction Angiogenesis is the formation and growing of new blood vessels from pre-existing vasculature during several normal and pathological situations (Goodwin 2007). This process involves a sequence of organized steps [...]

Byline: Azadeh. Motavallian, Sasan. Andalib, Golnaz. Vaseghi, Hamid. Mirmohammad-Sadeghi, Masoud. Amini Background: Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. [...]