Journal
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
Volume 18, Issue 1, Pages 67-74Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/1744666X.2022.2017281
Keywords
PCSK9; LDL; SLE; immunology; atherosclerosis
Categories
Funding
- Swedish Association Against Rheumatism
- Swedish Heart Lung Foundation
- EU (IMI
- Preciseads)
- King Gustav V:s 80year fund
- Amgen
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PCSK9 has pleiotropic effects, being involved in inflammation and immunity. Inhibition of PCSK9 is a potential therapy against inflammation and autoimmunity, and may play a role in diseases like systemic lupus erythematosus and rheumatoid arthritis.
Introduction Statins have pleiotropic effects, being both anti-inflammatory and immunomodulatory. Proprotein convertase subtilisin kexin 9 (PCSK9) targets the low-density lipoprotein receptor (LDLR), which increases LDL levels due to the lower expression of LDLR. Areas covered Inhibition of PCSK9 by the use of antibodies represents a novel principle to lower LDL levels. LDL may have other properties than being a cholesterol carrier but is well established as a risk factor for cardiovascular disease and atherosclerosis. In atherosclerosis, the plaques are characterized by activated T cells and dendritic cells (DCs), dead cells, and OxLDL. The latter may be an important cause of the inflammation typical of atherosclerosis, by promoting a proinflammatory immune activation. This is inhibited by PCSK9 inhibition, and an anti-inflammatory type of immune activation is induced. OxLDL is raised in systemic lupus erythematosus (SLE), where both CVD and atherosclerosis are much increased compared to the general population. PCSK9 is reported to be associated with disease activity and complications in SLE. Also in other rheumatoid arthritis, PCSK9 may play a role. Expert opinion PCSK9 has pleiotropic effects, being implicated in inflammation and immunity. Inhibition of PCSK9 is therefore interesting to study further as a potential therapy against inflammation and autoimmunity.
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