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PCSK9 inhibitors increase CD34+ but not other endothelial progenitor cells in patients with chronic coronary disease and increased Lp(a) values
ID Ugovšek, Sabina (Avtor), ID Rehberger Likozar, Andreja (Avtor), ID Levstek, Tina (Avtor), ID Trebušak Podkrajšek, Katarina (Avtor), ID Zupan, Janja (Avtor), ID Marka, Frieda (Avtor), ID Trimmel, Tamara (Avtor), ID Brekalo, Mira (Avtor), ID Speidl, Walter (Avtor), ID Hohensinner, Philipp (Avtor), ID Haider, Patrick (Avtor), ID Šebeštjen, Miran (Avtor)

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Izvleček
Background: Endothelial dysfunction is an independent predictor of cardiovascular events in patients with established atherosclerosis, while the circulating levels of endothelial progenitor cells (EPCs) reflect active endothelial function in heart failure patients. Although protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) lower lipid concentration and reduce cardiovascular events, their impact on endothelial function remains poorly understood. Purpose: We aimed to examine the effect of PCSK9i on the levels of EPCs in the peripheral blood of patients with chronic coronary disease and significantly elevated lipoprotein(a) (Lp(a)) concentrations. Methods: In this randomized, double-blind, placebo-controlled trial, we included 100 statin-treated patients at least 6 months post-myocardial infarction with elevated Lp(a) values. The patients received PCSK9i or a placebo every 2 weeks for 6 months. Biochemical and flow cytometric analyses of peripheral blood mononuclear cells were performed at baseline and after 6 months. Results: Treatment with PCSK9i increased the levels of mature EPCs (CD34+ ) compared with placebo (p = 0.003). In contrast, no significant effects were observed on early EPC subtypes (CD34+ CD309+, CD34+ CD133+, CD133+ CD309+, and CD133+; p = 0.611, p = 0.451, p = 0.739, and p = 0.161, respectively). The increase in mature EPCs (CD34+ ) levels did not correlate with changes in PCSK9 concentration. No associations were detected between changes in PCSK9 concentration and changes in levels of EPC subtypes predominantly expressing CD309, nor between changes in levels of any EPCs and lipoprotein concentration variations at baseline or at the end of the study. Conclusion: In patients with chronic coronary disease, treatment with PCSK9i increases circulating levels of mature CD34+ EPCs, without affecting other EPC subtypes.

Jezik:Angleški jezik
Ključne besede:endothelial function, endothelial progenitor cells, CD34+, lipoprotein(a), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i), myocardial infarction
Vrsta gradiva:Članek v reviji
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:MF - Medicinska fakulteta
FFA - Fakulteta za farmacijo
Status publikacije:Objavljeno
Različica publikacije:Objavljena publikacija
Leto izida:2026
Št. strani:12 str.
Številčenje:Vol. 10, art. a29012564
PID:20.500.12556/RUL-185247 Povezava se odpre v novem oknu
UDK:616.1
ISSN pri članku:2512-9465
DOI:10.1055/a-2901-2564 Povezava se odpre v novem oknu
COBISS.SI-ID:284577027 Povezava se odpre v novem oknu
Datum objave v RUL:04.08.2026
Število ogledov:280
Število prenosov:102
Metapodatki:XML DC-XML DC-RDF
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Gradivo je del revije

Naslov:TH open
Založnik:Thieme
ISSN:2512-9465
COBISS.SI-ID:131788291 Povezava se odpre v novem oknu

Licence

Licenca:CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
Povezava:http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
Opis:Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

Jezik:Slovenski jezik
Ključne besede:endotelijska funkcija, CD34+, lipoprotein (a), miokardni infarkt

Projekti

Financer:University Medical Centre Ljubljana
Številka projekta:20240051

Financer:University Medical Centre Ljubljana
Številka projekta:20250023

Financer:Amgen

Financer:Sanofi

Financer:Medizinische Universität Wien

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P3-0308
Naslov:Ateroskleroza in tromboza

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0170
Naslov:Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

Financer:ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:P1-0420
Naslov:Napredna imunološka zdravila in celični pristopi v farmaciji

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