Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies
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...
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Elsevier
2024-12-01
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| Series: | American Journal of Preventive Cardiology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666667724002642 |
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| author | Chen Gurevitz Osnat Itzhaki Ben Zadok Dorit Leshem-Lev Lital Hodeda Aviad Rotholz Ran Kornowski Alon Eisen |
| author_facet | Chen Gurevitz Osnat Itzhaki Ben Zadok Dorit Leshem-Lev Lital Hodeda Aviad Rotholz Ran Kornowski Alon Eisen |
| author_sort | Chen Gurevitz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-054f8318dfd64885bac1d66da9d970b8 |
| institution | DOAJ |
| issn | 2666-6677 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| series | American Journal of Preventive Cardiology |
| spelling | doaj-art-054f8318dfd64885bac1d66da9d970b82025-08-20T02:50:08ZengElsevierAmerican Journal of Preventive Cardiology2666-66772024-12-012010089610.1016/j.ajpc.2024.100896Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal AntibodiesChen Gurevitz0Osnat Itzhaki Ben Zadok1Dorit Leshem-Lev2Lital Hodeda3Aviad Rotholz4Ran Kornowski5Alon Eisen6Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Mount Sinai Fuster Heart Hospital, Ichan School of Medicine, New York, NY, USA; Corresponding author at: Cardiology Department, Rabin Medical Center, 39 Jabotinsky St. 49100 Petah Tikva, Israel.Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelFaculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, IsraelAzrieli Faculty of Medicine, Bar-Ilan University, Safed, IsraelDepartment of Cardiology, Rabin Medical Center, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Cardiology, Rabin Medical Center, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Cardiology, Rabin Medical Center, Petah Tikva, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelBackground: 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.http://www.sciencedirect.com/science/article/pii/S2666667724002642PCSK9 mAbCirculating endothelial progenitor cellsCoronary atherosclerotic disease |
| spellingShingle | Chen Gurevitz Osnat Itzhaki Ben Zadok Dorit Leshem-Lev Lital Hodeda Aviad Rotholz Ran Kornowski Alon Eisen Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies American Journal of Preventive Cardiology PCSK9 mAb Circulating endothelial progenitor cells Coronary atherosclerotic disease |
| title | Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies |
| title_full | Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies |
| title_fullStr | Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies |
| title_full_unstemmed | Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies |
| title_short | Circulating Endothelial Progenitor Cells in Patients with Established Cardiovascular Disease Treated with PCSK9 Monoclonal Antibodies |
| title_sort | circulating endothelial progenitor cells in patients with established cardiovascular disease treated with pcsk9 monoclonal antibodies |
| topic | PCSK9 mAb Circulating endothelial progenitor cells Coronary atherosclerotic disease |
| url | http://www.sciencedirect.com/science/article/pii/S2666667724002642 |
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