Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus

Abstract Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL cholesterol clearance and has been associated with cardiovascular risk. PCSK9 inhibitors increase in vivo circulating endothelial progenitor cells (EPCs), a subtype of immature cells involved in ongoing end...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Romina Tripaldi, Paola Lanuti, Paola Giustina Simeone, Rossella Liani, Giuseppina Bologna, Sonia Ciotti, Pasquale Simeone, Augusto Di Castelnuovo, Marco Marchisio, Francesco Cipollone, Francesca Santilli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/240420d0916c4f7da323f4207dc7fb87
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:240420d0916c4f7da323f4207dc7fb87
record_format	dspace
spelling	oai:doaj.org-article:240420d0916c4f7da323f4207dc7fb872021-12-02T14:29:03ZEndogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus10.1038/s41598-021-88941-x2045-2322https://doaj.org/article/240420d0916c4f7da323f4207dc7fb872021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88941-xhttps://doaj.org/toc/2045-2322Abstract Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL cholesterol clearance and has been associated with cardiovascular risk. PCSK9 inhibitors increase in vivo circulating endothelial progenitor cells (EPCs), a subtype of immature cells involved in ongoing endothelial repair. We hypothesized that the effect of PCSK9 on vascular homeostasis may be mediated by EPCs in patients with or without type 2 diabetes mellitus (T2DM). Eighty-two patients (45 with, 37 without T2DM) at high cardiovascular risk were enrolled in this observational study. Statin treatment was associated with higher circulating levels of PCSK9 in patients with and without T2DM (p < 0.001 and p = 0.036) and with reduced CD45neg/CD34bright (total EPC compartment) (p = 0.016) and CD45neg/CD34bright/CD146neg (early EPC) (p = 0.040) only among patients with T2DM. In the whole group of patients, statin treatment was the only independent predictor of low number of CD45neg/CD34bright (β = − 0.230; p = 0.038, adjusted R2 = 0.041). Among T2DM patients, PCSK9 circulating levels were inversely related and predicted both the number of CD45neg/CD34bright (β = − 0.438; p = 0.003, adjusted R2 = 0.173), and CD45neg/CD34bright/CD146neg (β = − 0.458; p = 0.002, adjusted R2 = 0.191) independently of age, gender, BMI and statin treatment. In high-risk T2DM patients, high endogenous levels of PCSK9 may have a detrimental effect on EPCs by reducing the endothelial repair and worsening the progression of atherothrombosis.Romina TripaldiPaola LanutiPaola Giustina SimeoneRossella LianiGiuseppina BolognaSonia CiottiPasquale SimeoneAugusto Di CastelnuovoMarco MarchisioFrancesco CipolloneFrancesca SantilliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Romina Tripaldi Paola Lanuti Paola Giustina Simeone Rossella Liani Giuseppina Bologna Sonia Ciotti Pasquale Simeone Augusto Di Castelnuovo Marco Marchisio Francesco Cipollone Francesca Santilli Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
description	Abstract Protease proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of LDL cholesterol clearance and has been associated with cardiovascular risk. PCSK9 inhibitors increase in vivo circulating endothelial progenitor cells (EPCs), a subtype of immature cells involved in ongoing endothelial repair. We hypothesized that the effect of PCSK9 on vascular homeostasis may be mediated by EPCs in patients with or without type 2 diabetes mellitus (T2DM). Eighty-two patients (45 with, 37 without T2DM) at high cardiovascular risk were enrolled in this observational study. Statin treatment was associated with higher circulating levels of PCSK9 in patients with and without T2DM (p < 0.001 and p = 0.036) and with reduced CD45neg/CD34bright (total EPC compartment) (p = 0.016) and CD45neg/CD34bright/CD146neg (early EPC) (p = 0.040) only among patients with T2DM. In the whole group of patients, statin treatment was the only independent predictor of low number of CD45neg/CD34bright (β = − 0.230; p = 0.038, adjusted R2 = 0.041). Among T2DM patients, PCSK9 circulating levels were inversely related and predicted both the number of CD45neg/CD34bright (β = − 0.438; p = 0.003, adjusted R2 = 0.173), and CD45neg/CD34bright/CD146neg (β = − 0.458; p = 0.002, adjusted R2 = 0.191) independently of age, gender, BMI and statin treatment. In high-risk T2DM patients, high endogenous levels of PCSK9 may have a detrimental effect on EPCs by reducing the endothelial repair and worsening the progression of atherothrombosis.
format	article
author	Romina Tripaldi Paola Lanuti Paola Giustina Simeone Rossella Liani Giuseppina Bologna Sonia Ciotti Pasquale Simeone Augusto Di Castelnuovo Marco Marchisio Francesco Cipollone Francesca Santilli
author_facet	Romina Tripaldi Paola Lanuti Paola Giustina Simeone Rossella Liani Giuseppina Bologna Sonia Ciotti Pasquale Simeone Augusto Di Castelnuovo Marco Marchisio Francesco Cipollone Francesca Santilli
author_sort	Romina Tripaldi
title	Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
title_short	Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
title_full	Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
title_fullStr	Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
title_full_unstemmed	Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus
title_sort	endogenous pcsk9 may influence circulating cd45neg/cd34bright and cd45neg/cd34bright/cd146neg cells in patients with type 2 diabetes mellitus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/240420d0916c4f7da323f4207dc7fb87
work_keys_str_mv	AT rominatripaldi endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT paolalanuti endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT paolagiustinasimeone endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT rossellaliani endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT giuseppinabologna endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT soniaciotti endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT pasqualesimeone endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT augustodicastelnuovo endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT marcomarchisio endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT francescocipollone endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus AT francescasantilli endogenouspcsk9mayinfluencecirculatingcd45negcd34brightandcd45negcd34brightcd146negcellsinpatientswithtype2diabetesmellitus
_version_	1718391239496171520

Endogenous PCSK9 may influence circulating CD45neg/CD34bright and CD45neg/CD34bright/CD146neg cells in patients with type 2 diabetes mellitus

Ejemplares similares