Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia

Nicola Ferri, Massimiliano Ruscica

Research output: Contribution to journalArticlepeer-review

Abstract

Low-density lipoprotein (LDL) cholesterol plays a pivotal role in the pathogenesis of atherosclerotic cardiovascular disease (CVD). The discovery that proprotein convertase subtilisin/kexin type 9 (PCSK9) represents a key regulator pathway for hepatic LDL receptor (LDLR) degradation sheds light on new uncovered issues regarding LDL-C homeostasis. Indeed, as confirmed by phase II and III clinical trials with monoclonal antibodies, targeting PCSK9 represents the newest and most promising pharmacological tool for the treatment of hypercholesterolemia and related CVD. However, clinical, genetic, and experimental evidence indicates that PCSK9 may be either a cause or an effect in the context of metabolic syndrome (MetS), a condition comprising a cluster of risk factors including insulin resistance, obesity, hypertension, and atherogenic dyslipidemia. The latter is characterized by a triad of hypertriglyceridemia, low plasma concentrations of high-density lipoproteins, and qualitative changes in LDLs. PCSK9 levels seem to correlate with many of these lipid parameters as well as with the insulin sensitivity indices, although the molecular mechanisms behind this association are still unknown or not completely elucidated. Nevertheless, this area of research represents an important starting point for a better understanding of the physiological role of PCSK9, also considering the recent approval of new therapies involving anti-PCSK9. Thus, in the present review, we will discuss the current knowledge on the role of PCSK9 in the context of MetS, alteration of lipids, glucose homeostasis, and inflammation.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalEndocrine
DOIs
Publication statusAccepted/In press - Apr 1 2016

Keywords

  • Hypertriglyceridemia
  • Insulin resistance
  • Metabolic syndrome and type 2 diabetes mellitus
  • PCSK9

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia'. Together they form a unique fingerprint.

Cite this