EHJ Bernelot 2017

Scientific publication in European Heart Journal

Sophie J. Bernelot Moens, junior researcher in the group of Prof. Erik Stroes and Prof. Menno de Winther (Academic Medical Center) recently published her results in European Heart Journal on how PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia.

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies increase hepatic low-density lipoprotein receptor expression and show potent low-density lipoprotein cholesterol (LDL-C) reduction of 60% (doi: 10.1161/CIRCULATIONAHA.112.144055) with only minimal changes in other lipoprotein fractions, such as high-density lipoprotein (HDL)-cholesterol and triglycerides. In contrast to statin therapy, the marked reduction in LDL-C upon PCSK9 monoclonal antibody administration is not accompanied by a C reactive protein (CRP) reduction (doi: 10.1111/bcp.12905), implying the absence of an anti-inflammatory effect by this class of therapeutic agents. However, the impact of PCSK9 monoclonal antibodies on other key inflammatory mediators, including monocytes, has not been reported before,

 

Migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. Since elevated LDL-C levels have been associated with activation of plasma monocytes, intensive LDL-C lowering may reverse these pro-inflammatory changes. Using  PCSK9 monoclonal antibodies  which selectively reduce LDL-C, Sophie J. Bernelot Moens studied the impact of LDL-C lowering on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH) not using statins due to statin-associated muscle symptoms.

In summary, the AMC group showed that lipid lowering with PCSK9 monoclonal antibodies reduces the pro-inflammatory phenotype of monocytes without affecting CRP, implying that potent lowering of LDL-C has an anti-inflammatory impact in hypercholesterolemic patients. These data highlight that inflammation is not solely captured by CRP measurement and warrant future investigations to assess the role of attenuating cellular inflammation in patients at high CV-risk.

 

Full article can be read here.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°667837.