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

Background

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

Conclusion

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.

References

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Find this article at Eur Heart J