PCSK9 Biomarker and Key Modulator for Cardiovascular Disorders: Heralding a New Therapeutic Era and Their Future Perspectives

Curr Mol Pharmacol. 2023;16(8):832-854. doi: 10.2174/1874467216666221202144813.

Abstract

Cardiovascular disorders (CVDs) are the leading cause of death worldwide and are accelerated via the low level of low-density lipoprotein-cholesterol (LDL-C). The proprotein convertase subtilis/kexin type9 (PCSK9), a vital regulator and a biomarker, circulates for the LDL-C and has the degradation capability of the low-density lipoprotein receptor (LDLR). PCSK9 has modulated the overall mechanism by transcription, secretion, clearance, or extracellular inactivation in the past few years.PCSK9 has specific pathophysiological roles in many cardiovascular cells. The initial data on the PCSK9 inhibitor, Evolocumab, has a specific reduction in the composite end-point, such as cardiovascular, myocardial, and stroke, while the rest of the data release is still under wait. Furthermore, it is witnessed that the U.S. and the European authorities have approved two humanized antibodies against the LDL-R binding site of PCSK9. This review highlighted the recent data findings on the PCSK9 and its regulation, focusing on cardiovascular disorders, and summarized the current clinical studies. Thus it provides a ray of hope to overcome statin intolerance and alternative approaches for PSCK9 inhibition and significantly reduce cardiovascular complications. This review plays a pivotal role for the researchers and scientists working on PCSK9 inhibitors to treat cardiovascular disorders.

Keywords: PCSK9; atherosclerosis; biomarker; cardiovascular disorders; clinical trial; low-density lipoproteincholesterol; modulator; monoclonal antibodies.

Publication types

  • Review

MeSH terms

  • Biomarkers
  • Cardiovascular Diseases* / drug therapy
  • Cholesterol, LDL
  • Humans
  • Proprotein Convertase 9* / metabolism
  • Proprotein Convertases

Substances

  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Cholesterol, LDL
  • Proprotein Convertases
  • Biomarkers