{"id":"7deef61dbedf","type":"article","url":"https://hartvaat.nl/2026/04/29/de-secretoire-pcsk-familie-van-moleculaire-schakelaars-tot-doelwit-voor-cardiova/","title":"De secretoire PCSK-familie: van moleculaire schakelaars tot doelwit voor cardiovasculaire therapie","title_en":"The secretory PCSK family in cardiovascular disease and beyond","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","internist"],"tags":["biomarkers-cardiovasculair","cardiale-amyloidose","cardiovasculaire-genetica","diabetes-type-1","ezetimibe","familiaire-hypercholesterolemie","familiaire-hypercholesterolemie-screening","gepersonaliseerde-geneeskunde","laminopathie","lipoproteïne-a","ouderen","pcsk9-remmers","pelacarsen","vrouwen"],"journal":"Atherosclerosis","doi":"https://www.atherosclerosis-journal.com/article/S0021-9150(26)00082-1/fulltext","source_url":"https://doi.org/https://www.atherosclerosis-journal.com/article/S0021-9150(26)00082-1/fulltext","authors":["Nabil G. Seidah"],"significance":5,"published":"2026-05-21","source_date":"2026-04-29","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ldl-cholesterol-mechanisme/","https://hartvaat.nl/kennis/lipiden/lp-a-verhoogd/"],"congress":"","summary_en":"Review in Atherosclerosis on the proprotein convertase family (PCSK1-PCSK9), identified between 1990 and 2003. These phylogenetically ancient serine proteases activate or regulate a wide range of secretory proteins — polypeptide hormones, growth factors, receptors, adhesion molecules, metalloproteinases and cytokines — by converting inactive precursors into their active forms. The authors place PCSK9, the best-known member due to its role in LDL-receptor degradation and its therapeutic exploitation via evolocumab, alirocumab and inclisiran, in the broader family context. The article discusses overlap with cardiovascular pathology and identifies emerging therapeutic targets within the PCSK family.","created":"2026-07-03T10:32:57Z","updated":"2026-07-03T13:31:52Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Overzichtsartikel in Atherosclerosis over de proproteïne convertase-familie (PCSK1-PCSK9), die in de periode 1990-2003 werd geïdentificeerd. Deze fylogenetisch oude serineproteasen activeren of reguleren een breed scala aan secretoire eiwitten — onder andere polypeptidehormonen, groeifactoren, receptoren, adhesiemoleculen, metalloproteïnasen en cytokinen — door inactieve precursors om te zetten in hun actieve vorm. De auteurs plaatsen PCSK9, het bekendste lid vanwege zijn rol in LDL-receptorafbraak en zijn therapeutische exploitatie via evolocumab, alirocumab en inclisiran, in de bredere familiecontext. Het artikel bespreekt de overlap met cardiovasculaire pathologie en signaleert nieuwe therapeutische aangrijpingspunten binnen de PCSK-familie.","abstract_original":"It took >20 years to discover the family of proteases implicated in the activation and/or regulation of the activity of secretory proteins, including polypeptide hormones, growth factors and receptors. From 1990 to 2003 the 9 members of the proprotein convertase (PC) family were identified and shown to be phylogenetically ancient serine proteases related to bacterial subtilases and to yeast Kexin, now called Proprotein Convertases related to Subtilsin and Kexin (PCSK1-PCSK9). Because many growth factors, receptors, adhesion molecules, metalloproteinases, cytokines, etc., are produced as inactive precursors, PCSKs are critical “master switches” that regulate when and where these proteins become active."}