Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9
Chen Gurevitz1,2,3, Osnat Itzhaki Ben Zadok1,2, Dorit Leshem-Lev2,4
1Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel.
Insights
Proprotein convertase subtilisin kexin type 9 monoclonal antibodies (PCSK9 mAb) increase circulating endothelial progenitor cells (cEPCs) in patients with cardiovascular disease. This suggests a potential pleiotropic class effect for PCSK9 mAb therapies like evolocumab and alirocumab.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Pharmacology
Background:
- Circulating endothelial progenitor cells (cEPCs) play a vital role in vascular repair.
- cEPCs are associated with cardiovascular protection.
- The impact of PCSK9 monoclonal antibodies (mAbs) on cEPCs is not fully understood.
Purpose of the Study:
- To investigate the effect of PCSK9 mAbs on cEPCs in adults with hypercholesterolemia and cardiovascular disease.
- To determine if PCSK9 mAbs have a pleiotropic class effect on cEPCs.
Main Methods:
- A prospective, non-interventional study was conducted on 51 patients with cardiovascular disease treated with evolocumab or alirocumab.
- cEPCs were analyzed at baseline, 1-month, and 3-months using flow cytometry (CD34/CD133, VEGFR-2 expression).
- Functional assessments included colony-forming units (CFUs) and MTT assays for cEPC viability.
Main Results:
- PCSK9 mAb therapy significantly increased CD34+/VEGFR-2+ and CD133+/VEGFR-2+ cEPC levels (p < 0.001).
- Functional assessments showed a significant increase in EPC-CFUs and MTT assay results (p < 0.001).
- Both evolocumab and alirocumab demonstrated similar increases in cEPC levels and function.
Conclusions:
- Treatment with PCSK9 mAbs leads to increased levels and function of cEPCs in patients with hypercholesterolemia and cardiovascular disease.
- These findings suggest a novel, pleiotropic class effect of PCSK9 mAbs.
- The observed effects were consistent across both evolocumab and alirocumab treatments.
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.
