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

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An Erratum to this article was published on 05 October 2016

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.

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Acknowledgments

Fondazione Cariplo Grants Rif. 2012-0549 (N.F.) and Rif. 2015-0552 (M.R.) and Piano di Sostegno per la Ricerca, Università degli Studi di Milano, 2015-2017 - Linea 2 (Azione A) (M.R.).

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  1. Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Largo Meneghetti 2, 35131, Padua, Italy

    Nicola Ferri

  2. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy

    Massimiliano Ruscica

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Ferri, N., Ruscica, M. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia. Endocrine 54, 588–601 (2016). https://doi.org/10.1007/s12020-016-0939-0

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