Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units

Background: Circulating CD34+ progenitor cells (CD34+CPCs) are characterized by pronounced tissue regeneration activity. Dyslipidemic subjects seemed to have reduced CD34+CPCs, and statin therapy appeared to restore their levels. We aimed to evaluate the effects of PCSK9 inhibitors (PCSK9-i) on CD34...

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Main Authors: Roberto Scicali, Giuseppe Mandraffino, Michele Scuruchi, Alberto Lo Gullo, Antonino Di Pino, Viviana Ferrara, Carmela Morace, Caterina Oriana Aragona, Giovanni Squadrito, Francesco Purrello, Salvatore Piro
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/7/1715
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author Roberto Scicali
Giuseppe Mandraffino
Michele Scuruchi
Alberto Lo Gullo
Antonino Di Pino
Viviana Ferrara
Carmela Morace
Caterina Oriana Aragona
Giovanni Squadrito
Francesco Purrello
Salvatore Piro
author_facet Roberto Scicali
Giuseppe Mandraffino
Michele Scuruchi
Alberto Lo Gullo
Antonino Di Pino
Viviana Ferrara
Carmela Morace
Caterina Oriana Aragona
Giovanni Squadrito
Francesco Purrello
Salvatore Piro
author_sort Roberto Scicali
collection DOAJ
description Background: Circulating CD34+ progenitor cells (CD34+CPCs) are characterized by pronounced tissue regeneration activity. Dyslipidemic subjects seemed to have reduced CD34+CPCs, and statin therapy appeared to restore their levels. We aimed to evaluate the effects of PCSK9 inhibitors (PCSK9-i) on CD34+CPCs and pulse wave velocity (PWV) in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. Methods: We determined CD34+ cell count and its change after PCSK9-i in 30 selected HeFH subjects and 30 healthy controls. Lipid profile and PWV were evaluated at baseline (T0), 6 months after intensive lipid lowering strategy (statin plus ezetimibe, T1), and after 6 months of optimized therapy with PCSK9-i (T2); CD34+ cell count was reported at T1 and T2. Results: At T1, the median value of CD34+ cells was not significantly different between HeFH subjects and controls, and the same result was obtained at T2. PWV was significantly reduced at T1 (ΔPWV − 14.8%, <i>p</i> < 0.001 vs. T0) and T2 (ΔPWV − 10.96%, <i>p</i> < 0.001 vs. T1). Dividing HeFH subjects into two groups of high- and low-CD34+ cell count, CD34+CPCs appeared to be polarized with a significant difference between the two groups (1.2 (0.46) vs. 4.74 (1.92), <i>p</i> < 0.001), also with respect to controls (both <i>p</i> < 0.001). This polarization was no longer observed at T2, and neither with respect to controls. ΔCD34+ was +67.4% in the low-CD34+ group and −39.24% in the high-CD34+ group (<i>p</i> < 0.001). Lastly, we found a significant correlation between ΔCD34+ cell number and ΔPWV in HeFH subjects (rho = −0.365, <i>p</i> < 0.05), particularly in the low-CD34+ group (rho = −0.681, <i>p</i> < 0.001). Conclusion: PCSK9-i exhibited favorable effects on CD34 + CPCs as was on PWV values in a cohort of FH subjects. Our preliminary findings suggest a possible positive role of this novel lipid-lowering strategy on vascular homeostasis.
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spelling doaj.art-3e903c19518a4177b3f4a5bfba1931322023-11-30T22:51:25ZengMDPI AGBiomedicines2227-90592022-07-01107171510.3390/biomedicines10071715Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid UnitsRoberto Scicali0Giuseppe Mandraffino1Michele Scuruchi2Alberto Lo Gullo3Antonino Di Pino4Viviana Ferrara5Carmela Morace6Caterina Oriana Aragona7Giovanni Squadrito8Francesco Purrello9Salvatore Piro10Department of Clinical and Experimental Medicine, University of Catania, 95100 Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, University Hospital G. Martino, Lipid Center, 98100 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, University Hospital G. Martino, Lipid Center, 98100 Messina, ItalyUnit of Rheumatology, Department of Medicine, ARNAS Garibaldi Hospital, 95100 Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, 95100 Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, 95100 Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, University Hospital G. Martino, Lipid Center, 98100 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, University Hospital G. Martino, Lipid Center, 98100 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Messina, University Hospital G. Martino, Lipid Center, 98100 Messina, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, 95100 Catania, ItalyDepartment of Clinical and Experimental Medicine, University of Catania, 95100 Catania, ItalyBackground: Circulating CD34+ progenitor cells (CD34+CPCs) are characterized by pronounced tissue regeneration activity. Dyslipidemic subjects seemed to have reduced CD34+CPCs, and statin therapy appeared to restore their levels. We aimed to evaluate the effects of PCSK9 inhibitors (PCSK9-i) on CD34+CPCs and pulse wave velocity (PWV) in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. Methods: We determined CD34+ cell count and its change after PCSK9-i in 30 selected HeFH subjects and 30 healthy controls. Lipid profile and PWV were evaluated at baseline (T0), 6 months after intensive lipid lowering strategy (statin plus ezetimibe, T1), and after 6 months of optimized therapy with PCSK9-i (T2); CD34+ cell count was reported at T1 and T2. Results: At T1, the median value of CD34+ cells was not significantly different between HeFH subjects and controls, and the same result was obtained at T2. PWV was significantly reduced at T1 (ΔPWV − 14.8%, <i>p</i> < 0.001 vs. T0) and T2 (ΔPWV − 10.96%, <i>p</i> < 0.001 vs. T1). Dividing HeFH subjects into two groups of high- and low-CD34+ cell count, CD34+CPCs appeared to be polarized with a significant difference between the two groups (1.2 (0.46) vs. 4.74 (1.92), <i>p</i> < 0.001), also with respect to controls (both <i>p</i> < 0.001). This polarization was no longer observed at T2, and neither with respect to controls. ΔCD34+ was +67.4% in the low-CD34+ group and −39.24% in the high-CD34+ group (<i>p</i> < 0.001). Lastly, we found a significant correlation between ΔCD34+ cell number and ΔPWV in HeFH subjects (rho = −0.365, <i>p</i> < 0.05), particularly in the low-CD34+ group (rho = −0.681, <i>p</i> < 0.001). Conclusion: PCSK9-i exhibited favorable effects on CD34 + CPCs as was on PWV values in a cohort of FH subjects. Our preliminary findings suggest a possible positive role of this novel lipid-lowering strategy on vascular homeostasis.https://www.mdpi.com/2227-9059/10/7/1715circulating CD34+ cellsfamilial hypercholesterolemiaPCSK9 inhibitorspulse wave velocitycardiovascular risk
spellingShingle Roberto Scicali
Giuseppe Mandraffino
Michele Scuruchi
Alberto Lo Gullo
Antonino Di Pino
Viviana Ferrara
Carmela Morace
Caterina Oriana Aragona
Giovanni Squadrito
Francesco Purrello
Salvatore Piro
Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
Biomedicines
circulating CD34+ cells
familial hypercholesterolemia
PCSK9 inhibitors
pulse wave velocity
cardiovascular risk
title Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
title_full Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
title_fullStr Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
title_full_unstemmed Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
title_short Effects of Lipid Lowering Therapy Optimization by PCSK9 Inhibitors on Circulating CD34+ Cells and Pulse Wave Velocity in Familial Hypercholesterolemia Subjects without Atherosclerotic Cardiovascular Disease: Real-World Data from Two Lipid Units
title_sort effects of lipid lowering therapy optimization by pcsk9 inhibitors on circulating cd34 cells and pulse wave velocity in familial hypercholesterolemia subjects without atherosclerotic cardiovascular disease real world data from two lipid units
topic circulating CD34+ cells
familial hypercholesterolemia
PCSK9 inhibitors
pulse wave velocity
cardiovascular risk
url https://www.mdpi.com/2227-9059/10/7/1715
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