Hypercholesterolemia impairs the Glucagon-like peptide 1 action on platelets: Effects of a lipid-lowering treatment with simvastatin.
Thromb Res
; 180: 74-85, 2019 Aug.
Article
em En
| MEDLINE
| ID: mdl-31229924
ABSTRACT
BACKGROUND:
The incretin hormone Glucagon-like peptide 1(GLP-1) plays a pivotal role in maintaining glucose homeostasis with effects also on the cardiovascular system. GLP-1 influences platelet functions by increasing the inhibitory action of nitric oxide (NO) and reducing oxidative stress. To date, the role of hypercholesterolemia (HyC) on platelet GLP-1 effects needs to be elucidated.METHODS:
Forty-five subjects with primary HyC and twenty normocholesterolemic controls (NoC) were enrolled. In platelets from all subjects, the native GLP-1 (7-36), the truncated GLP-1 (9-36) and the GLP-1 analogue Liraglutide were evaluated in their ability to interfere with the activation of NO/PKG/VASP, PI-3K/Akt e MAPK/ERK-1/2 pathways and oxidative stress. Furthermore, in HyC subjects the role of a lipid-lowering therapy with statin on GLP-1 related peptide effects on platelet function was evaluated.RESULTS:
Unlike in NoC, in platelets from HyC subjects the GLP-1 related peptides GLP-1 (7-36), GLP-1 (9-36) and Liraglutide all failed to i) increase the antiaggregating effects of NO and the NO-induced VASP-ser239 phosphorylation, ii) decrease phosphorylation levels of Akt and ERK-2 and iii) reduce reactive oxygen species (ROS) generation. The treatment with simvastatin (40â¯mg/die) in HyC (nâ¯=â¯18) significantly reduced total and LDL cholesterol levels, platelet aggregability/activation, ROS production and NO action but did not modify platelet sensitivity to the GLP-1 effects.CONCLUSION:
Collectively, these results indicate that hypercholesterolemia per se is characterized by a resistance to GLP-1 effects on platelets and this impairment is not corrected by treatment with simvastatin.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Plaquetas
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Sinvastatina
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Peptídeo 1 Semelhante ao Glucagon
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Hipercolesterolemia
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Hipolipemiantes
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Thromb Res
Ano de publicação:
2019
Tipo de documento:
Article