The effect of statin therapy withdrawal on monocyte subsets

Authors

  • Anthony S. Jaipersad,

    1. University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
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    • Joint first authors.

  • Eduard Shantsila,

    Corresponding author
    1. University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
    • Correspondence to: Dr Eduard Shantsila, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, UK. Tel.: +44 121 507 5080; fax: +44 121 554 4083; e-mail: e.shantsila@bham.ac.uk

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    • Joint first authors.

  • Andrew Blann,

    1. University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
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  • Gregory Y. H. Lip

    1. University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
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Abstract

Background

Three functionally distinct monocyte subsets have been identified. Statins are of undoubted effect in atherosclerosis and have numerous pleiotropic effects that contribute to their clinical success, but the effect of these drugs on monocyte subsets is unclear. We hypothesised a beneficial effect of statins on key receptor expression by monocyte subsets.

Material and methods

Effects of temporal (2 weeks) cessation of statin therapy by 66 patients with stable coronary artery disease on monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2− (Mon3)], their aggregates with platelets and their expression of a number of receptors involved in inflammation (IL-6 receptor), adhesion [vascular cell adhesion molecule (VCAM)], angiogenesis [vascular endothelial growth factor (VEGF)] and repair were assessed by flow cytometry.

Results

Statin cessation did not lead to any significant changes in absolute numbers of monocyte subsets or the degree of their aggregation with platelets. All monocyte subsets showed significant downregulation of expression of vascular endothelial factor receptor 2, Tie2 and Toll-like receptor-4 (TLR4; all changes P < 0·01). Expression of CXCR4 was only reduced in Mon1 cells (P = 0·013). There was no significant change in the expression of CD14, CD16, CCR4, IL6 receptor and VCAM (all P = NS).

Conclusions

Statin withdrawal does not affect counts of any of monocyte subsets, but leads to downregulation of expression of TLR4 and receptors related to angiogenesis on all subsets, as well as a decrease in density of CXCR4 expression on ‘classical’ Mon1. These data provide further support of pleiotropic effects of statins and their effects on monocyte pro-angiogenic and proreparative characteristics.

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