Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies

Abstract

Background

The role of circulating endothelial progenitor cells (cEPCs) in vascular repair and their association to cardiovascular protection is well established.

Objectives

We examined the effect of proprotein convertase subtilisin kexin type 9 monoclonal antibodies (PCSK9 mAb) on cEPCs in adults with hypercholesterolemia and cardiovascular disease, aiming to establish a pleotropic class effect.

Methods

Non-interventional prospective study in patients with cardiovascular disease treated with either evolocumab or alirocumab. Patients were sampled for cEPCs at baseline, 1- and 3-months following initiation of PCSK9 mAb. cEPCs were assessed using flow cytometry by expression of CD34/CD133 and vascular endothelial growth factor receptor (VEGFR)-2, and functionally by formation of colony forming units (CFUs) and by Mitochondrial Tetrazolium (MTT) assay, indicative of cEPCs viability.

Results

51 patients (median age 67 (IQR 63,74) years;63 % male, median low-density lipoprotein-cholesterol (LDL-C) 125 (102,165) mg/dL) were initiated on PCSK9 mAb therapy (evolocumab n = 22, alirocumab n = 29) for secondary prevention. Following 3-month treatment with PCSK9 mAb, there was an increase in CD34⁽⁺⁾VEGFR-2⁽⁺⁾ and CD133⁽⁺⁾VEGFR-2⁽⁺⁾ levels (0.50 % [IQR 0.30,1.04] to 1.36 % [0.89, 1.73], p < 0.001 and 0.57 % [0.25,0.88] to 1.18 % [0.74,1.66], p < 0.001, respectively). Functionally, increase in EPCs-CFUs was evident (0.5 [0.0,1.0] to 2.0 [1.5,2.5], p < 0.001) with concomitant increase in MTT (0.11 [0.09,0.15] to 0.17 [0.12,0.21], p < 0.001). Stratifying by PCSK9 mAb, both agents were associated with an increase in cEPCs level and function.

Conclusions

In hypercholesterolemic patients with cardiovascular disease treated with PCSK9 mAb, there is an increase in cEPCs levels and function from baseline levels. These findings, which persist in both evolocumab and alirocumab, might suggest a novel pleiotropic class effect.