Moderate to high concentrations of high-density lipoprotein from healthy subjects paradoxically impair human endothelial progenitor cells and related angiogenesis by activating Rho-associated kinase pathways.
Arterioscler Thromb Vasc Biol
; 32(10): 2405-17, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22904272
ABSTRACT
OBJECTIVE:
Recent clinical evidence has failed to demonstrate the benefits of elevation of serum high-density lipoprotein (HDL), suggesting potential loss of protective effects of HDL at high concentrations. This study aimed to investigate the concentration-related effects of HDL on in vitro and in vivo functions of human endothelial progenitor cells (EPCs) and related angiogenesis. METHODS ANDRESULTS:
Early and late outgrowth EPCs were generated from human circulating mononuclear cells. Oxidized low-density lipoprotein reduced viability of late outgrowth EPCs, which was reversed dose dependently by HDL. In the absence of oxidized low-density lipoprotein, HDL at low concentrations (5-50 µg/mL, equal to 0.5-5 mg/dL in human) enhanced EPC tube formation by activating phosphatidylinositol-3 kinase/Akt/endothelial NO synthase pathways. Moderate to high concentrations (400-800 µg/mL) of HDL paradoxically enhanced EPC senescence and impaired tube formation by activating Rho-associated kinase (ROCK) and inhibiting phosphatidylinositol-3 kinase/Akt and p38 mitogen-activated protein kinase pathways. Rho-associated kinase inhibitors, either Y27632 or statins, prevented high HDL-induced EPC senescence and improved in vitro tube formation, as well as in vivo capacity of angiogenesis of EPCs.CONCLUSIONS:
While protecting EPCs from the injury of oxidized low-density lipoprotein, moderate to high concentrations of HDL paradoxically impaired EPCs and related angiogenesis in the absence of oxidized low-density lipoprotein by activating Rho-associated kinase pathways, providing mechanistic evidence of potential hazard effects of HDL.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Endotélio Vascular
/
Transdução de Sinais
/
Neovascularização Fisiológica
/
Quinases Associadas a rho
/
Lipoproteínas HDL
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article