Clinical aspects of PCSK9

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a circulating protein that impairs LDL clearance by promoting the LDL receptor (LDLR) degradation. PCSK9 has emerged as a new pharmacological target for hypercholesterolemia, and different PCSK9 inhibitors are now evaluated in clinical trials. Here, we propose an overview of the clinical perspectives of PCSK9. First, we describe the clinical features of patients with PCSK9 mutations, and how these variations impact the cardiovascular risk. Then, we extensively discuss the potential role of circulating PCSK9 as a new biomarker of lipid metabolism. Indeed, many studies conducted in healthy and type 2 diabetic patients have tested the association of circulating PCSK9 with LDL-cholesterol as well as with multiple metabolic parameters. The overall picture of the clinical relevance of circulating PCSK9 is complicated by the effect of nutritional status and hypolipidemic drugs such as statins, fibrates, ezetimibe on plasma PCSK9 concentrations. Finally, we present a brief overview of the available therapeutic strategies to inhibit PCSK9.