Hypercholesterolemia impairs the Glucagon-like peptide 1 action on platelets: Effects of a lipid-lowering treatment with simvastatin
| Autor: | Cristina Barale, Chiara Frascaroli, Isabella Russo, Franco Cavalot |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Blood Platelets Male Platelets Simvastatin endocrine system Statin Platelet Aggregation Glucagon-like peptide 1 Hypercholesterolemia Nitric oxide Reactive oxygen species medicine.drug_class 030204 cardiovascular system & hematology Pharmacology medicine.disease_cause 03 medical and health sciences 0302 clinical medicine medicine Humans Glucose homeostasis Platelet Phosphorylation Hypolipidemic Agents chemistry.chemical_classification Liraglutide digestive oral and skin physiology Hematology Middle Aged Glucagon-like peptide-1 Oxidative Stress chemistry 030220 oncology & carcinogenesis Female hormones hormone substitutes and hormone antagonists Oxidative stress medicine.drug |
| Zdroj: | Thrombosis Research. 180:74-85 |
| ISSN: | 0049-3848 |
| Popis: | 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 (40 mg/die) in HyC (n = 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. |
| Databáze: | OpenAIRE |
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