Hypercholesterolemia impairs the Glucagon-like peptide 1 action on platelets: Effects of a lipid-lowering treatment with simvastatin. Issue 180 (August 2019)

• Record Type: Journal Article
• Authors: Barale, Cristina; Frascaroli, Chiara; Cavalot, Franco; Russo, Isabella
• Is Part Of: Thrombosis research. Issue 180(2019)
• Page Start: 74
• Page End: 85
• Publication Date: 2019-08
• Subjects: Glucagon-like peptide 1 -- Platelets -- Nitric oxide -- Hypercholesterolemia -- Reactive oxygen species -- Simvastatin; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2019.06.010
• Languages: English
• ISSNs: 0049-3848

Abstract

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 (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. Highlights: GLP-1 increases the inhibition by NO and reduces activation of platelets. In hypercholesterolemia the GLP-1 effects on platelets are deeply reduced. Simvastatin increases platelet sensitivity to NO and reduces platelet activation. The resistance to GLP-1 effects on platelets is not affected by simvastatin therapy.