Key result
Elevated PCSK9 impairs endotoxin clearance and worsens inflammation in sepsis and ARDS.
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PCSK9 is increasingly recognized for its inflammatory role in critical illnesses like sepsis and ARDS, highlighting a need to explore its extra-hepatic effects and potential therapeutic inhibition.
Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9) is a key regulator of lipid metabolism, binding to the low-density lipoprotein receptor (LDLR) on the cell surface and preventing its recycling, thereby reducing clearance of LDL cholesterol (LDLc) from the circulation. For this reason, it constitutes an alternative therapeutic target for the control of hypercholesterolaemia, with the development of monoclonal antibodies against PCSK9 occurring within 12 years of the protein's discovery. Recent research has also suggested an inflammatory role played by PCSK9, with elevated plasma levels identified in critical illnesses such as sepsis and Acute Respiratory Distress Syndrome, where PCSK9 is thought to reduce bacterial endotoxin clearance and may exacerbate inflammation. Further work is required in order to clarify the exact role played by PCSK9 in extra-hepatic tissues, and the potential benefits of its pharmacological inhibition.
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Crossley et al. (2025) conducted a review in Critical illnesses such as sepsis and Acute Respiratory Distress Syndrome. PCSK9 was evaluated. Elevated plasma levels of PCSK9 in critical illnesses such as sepsis and ARDS are thought to reduce bacterial endotoxin clearance and exacerbate inflammation.
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