Physicians' Academy for Cardiovascular Education

Anti-inflammatory changes in response to PCSK9 antibody treatment in monocytes of FH patients

PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia

Bernelot Moens SJ, Neele AE, Kroon J et al., - Eur Heart J (2017) 00, 1–10. doi:10.1093/eurheartj/ehx002


As the role of inflammation in atherogenesis cannot be explained by a causal role for C-reactive protein, focus has shifted towards immune cells [1,2]. Monocytes infiltrate atherosclerotic lesions [3] and monocyte-derived macrophages contribute to a local pro-inflammatory milieu in the plaque [4]. The receptor for monocyte chemo-attractant protein 1 (MCP-1), C-C chemokine receptor type 2 (CCR2) plays an important role in the recruitment of monocytes to the arterial wall [5]. Higher CCR2 expression is seen in patients with hypercholesterolaemia [6,7].

As opposed to statins, treatment with PCSK9 antibodies (mAbs) does not lead to a CRP reduction in addition to the LDL-c reduction [8]. The effect of PCSK9 mAbs on other inflammatory mediators has not been reported on.

This study assessed the impact of elevated LDL-c levels on monocyte phenotype and function in patients with familial hypercholesterolaemia (FH, n=22), who are not receiving statins due to statin-associated muscle symptoms (SAMS), and compared this to matched normolipidaemic control subjects (n=18). The effect of 24 weeks PCSK9 mAbs (alirocumab: n=10, evolocumab: n=7) in FH patients on their monocytes was assessed, as compared with FH patients on stable statin treatment.

Main results


Monocytes from FH patients not on statin therapy due to SAMS, show pro-inflammatory and migratory changes and an increase in cytoplasmic lipid droplets. The observations suggest a direct relation between intracellular lipid accumulation and inflammatory changes in monocytes. After 24-week treatment with a PCSK9 mAb anti-inflammatory changes were seen in monocyte migratory capacity, lipid content, and inflammatory responsiveness, towards a profile seen in FH patients on stable statin use. These changes were seen in the absence of a decrease in CRP levels.


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Find this article at Eur Heart J