Dasom Shin, Soungchan Kim, Hwan Lee, Hyun-Chae Lee, Jaewon Lee, Hyun-Woo Park, Mina Fukai, EunByule Choi, Subin Choi, Bon-Jun Koo, Ji-Hoon Yu, Gyurae No, Sungyoon Cho, Chan Woo Kim, Dohyun Han, Hyun-Duk Jang, Hyo-Soo Kim
Proprotein convertase subtilisin/kexin type-9 (PCSK9) binds to and degrades low-density lipoprotein (LDL) receptor, leading to increase of LDL cholesterol in blood. Its blockers have emerged as promising therapeutics for cardiovascular diseases. Here we show that PCSK9 itself directly induces inflammation and aggravates atherosclerosis independently of the LDL receptor. PCSK9 exacerbates atherosclerosis in LDL receptor knockout mice. Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9 and indispensable for the inflammatory action of PCSK9, including induction of cytokines, Toll like receptor 4, and scavenger receptors, enhancing the uptake of oxidized LDL...
March 30, 2024: Nature Communications