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PCSK9 and inflammation. Maybe a role in autoimmune diseases? Focus on rheumatoid arthritis and systemic lupus erythematosus

Author(s):

Stefano Ministrini and Federico Carbone*  

Abstract:


Despite a clear epidemiological link between autoimmune disease and cardiovascular (CV) risk exists, pathophysiological explanations are extremely complex and far from being elucidated. Dysregulation of metabolic pathways and chronic low-grade inflammation represent common pathways, but CV risk still remains underestimated in patients with autoimmune diseas. Among different candidate mediators, pro-protein convertase subtilisin/kexin type 9 (PCSK9) is attracting a growing attention, due to a combined effect on lipid metabolism and inflammatory response. Study on PCSK9 inhibitors have established a clear benefit on CV outcome without an established effect on inflammation. Conversely, evidence from sepsis and HIV infection strongly support a pro-inflammatory role of PCSK9. Still uncertain is instead the role of PCSK9 in autoimmune disease. So far reported clinical findings are controversial and likely reflect the poor knowledge of PCSK9 activity on monocyte/macrophage migration and activation. The complex signaling network around PCSK9 synthesis and metabolism may also have a role, especially concerning the involvement of scavenger receptors such as CD36. Such complexity in PCSK9 signaling seems particularly evident in autoimmune disease model. This would also potentially explain the observed independency between lipid profile and PCSK9 levels, the so-called “lipid paradox”. In this narrative review we will summarize the current knowledge about the complex network of PCSK9 signaling. We will focus of upstream and downstream pathways with potential implication in autoimmune disease and potential effects of PCSK9 inhibiting strategies.

Keywords:

PCSK9, inflammation, autoimmune disease, rheumatoid arthritis, sepsis, cytokines

Affiliation:

Internal Medicine, Angiology and Atherosclerosis; Department of Medicine and Surgery, University of Perugia, p.le Gambuli 1, 06132 Perugia, First Clinic of internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa



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