Effects of PCSK9 on thrombosis and haemostasis in a variety of metabolic states: Lipids and beyond (Review)

Int J Mol Med. 2024 Jun;53(6):57. doi: 10.3892/ijmm.2024.5381. Epub 2024 May 17.

Abstract

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are widely recognised as being able to induce a potent reduction in low‑density lipoprotein‑cholesterol. An increasing number of studies have suggested that PCSK9 also influences the haemostatic system by altering platelet function and the coagulation cascade. These findings have significant implications for anti‑PCSK9 therapy in patients with specific coagulation conditions, including expanded indications, dose adjustments and drug interactions. The present review summarises the changes in PCSK9 levels in individuals with liver diseases, chronic kidney diseases, diabetes mellitus, cancer and other disease states, and discusses their impact on thrombosis and haemostasis. Furthermore, the structure, effects and regulatory mechanisms of PCSK9 on platelets, coagulation factors, inflammatory cells and endothelial cells during coagulation and haemostasis are described.

Keywords: haemostasis; metabolic states; proprotein convertase subtilisin kexin type 9; thrombosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Platelets / metabolism
  • Hemostasis* / drug effects
  • Humans
  • Lipid Metabolism / drug effects
  • PCSK9 Inhibitors
  • Proprotein Convertase 9* / metabolism
  • Thrombosis* / drug therapy
  • Thrombosis* / metabolism

Substances

  • PCSK9 protein, human

Grants and funding

The present study was supported by the National Key Research and Development Program of China (grant nos. 2021YFC2500500 and 2021YFC2500503), the National High Level Hospital Clinical Research Funding (Scientific Research Fund of Peking University First Hospital (grant no. 2022SF15), and the National Natural Science Foundation of China General Program (grant nos. 82073935 and 82373950).