• Association between Proprotein convertase subtilisin/kexin type 9 with atherosclerosis
  • Ali Nosrati Andevari,1,* Durdi Qujeq,2
    1. Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
    2. Department of Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran


  • Introduction: In 2003, Seidah et al discovered a new element in the proprotein convertase family. The gene encoding this enzyme was found to be more expressed during apoptosis of brain cells. Since it was the ninth element of the proprotein convertases family, it was named proprotein convertase subtilisin/kexin type 9 (PCSK9), besides convertase neural apoptosis-regulated convertase 1 (NARC-1). PCSK9 is most commonly expressed in the liver. PCSK9 has the primary function of regulating the cellular low-density lipoprotein receptor (LDLR). The deposition of lipids, particularly LDL and Lp(a), in the walls of arteries is the cause of atherosclerosis. The aim of this study was to evaluate the association between PCSK9 with atherosclerosis.
  • Methods: For this review, 50 articles were found in the first stage. Strategy search in this case was as follows: the first two words (PCSK9 and atherosclerosis) in the mesh PubMed dataset were initially identified. Then, we combined two words in the pattern of using AND and OR. This review utilized human, animal, and in vitro studies.
  • Results: According to the conducted studies, PCSK9 promotes LDLR degradation through both intracellular and extracellular pathways. It leads to increased production and secretion of VLDL and LP(a). Thus, it increases the serum level of LDL and LP(a). The accumulation of LDL and Lp(a) in endothelial cells leads to the formation of foam cells. Moreover, by binding to Toll-like receptors (TLRs), PCSK9 acts as a mediator of inflammatory responses. It is responsible for platelet activation and thrombosis by interacting with CD36 receptors. Also, the levels of coagulation factors FVIII and tissue factor (TF) were raised by PCSK9. It was shown, that PCSK9 prevented cholesterol efflux from macrophages by inhibiting ABCA1 expression. On the other hand, PCSK9 inhibits the formation of foam cells through the degradation of LDLR and CD36 in macrophages.
  • Conclusion: PCSK9 has conflicting roles in the process of atherosclerosis
  • Keywords: PCSK9, atherosclerosis, thrombosis, foam cell