The role of endothelial nitric oxide in the anti-restenotic effects of liraglutide in a mouse model of restenosis

Kushima, Hideki; Mori, Yusaku; Koshibu, Masakazu; Hiromura, Munenori; Kohashi, Kenichi; Terasaki, Michishige; Fukui, Tetsuya; Hirano, Tsutomu

doi:10.1186/s12933-017-0603-x

Cited by 41 publications

(44 citation statements)

References 58 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exenatide has direct vascular protective effects on endothelial cells and modulates vascular inflammation [22][23][24]. Liraglutide is a GLP-1-derived peptide, and it has been shown that liraglutide could also enhance endothelial function and suppress endothelial inflammation and atherosclerosis in animal models [25][26][27][28]. Lixisenatide has been evaluated in broad clinical studies.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: GLP-1 receptor agonist lixisenatide protects against high free fatty acids-induced oxidative stress and inflammatory response

Zhao

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Increased free fatty acids (FFA) are one of the risk factors for type 2 diabetes. FFA also contribute to endothelial dysfunction in both the prediabetes and diabetes conditions. Therefore, FFA are an important link between diabetes and endothelial dysfunction. In therapeutic application, GLP-1 receptor agonists have been implemented to lower blood glucose in diabetes. Here, we investigate the role of the common clinically used GLP-1 receptor agonist lixisenatide in endothelial cells. We demonstrate that lixisenatide could protect endothelial cells from high FFA-induced toxicity and cell death. Lixisenatide also suppresses FFA-caused cellular ROS generation and production of the lipid oxidation byproduct 4-HNE. Lixisenatide inhibits FFA-triggered production of TNF-a, IL-6, VCAM-1 and ICAM-1. The presence of lixisenatide in co-culture experiments suppresses adhesion of monocytes to endothelial cells. Moreover, lixisenatide ameliorates FFA-induced decreased eNOS phosphorylation and NO reduction. We also demonstrate that lixisenatide inhibits FFA-induced IjBa activation, nuclear p65 translocation and NF-jB activation. This evidence indicates that lixisenatide suppresses activation of the NF-jB pathway in endothelial cells. Collectively, our findings suggest that lixisenatide might have therapeutic potential to modulate diabetes-associated vascular complications.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: GLP-1 receptor agonist lixisenatide protects against high free fatty acids-induced oxidative stress and inflammatory response

Zhao

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

show abstract

“…Also, NO inhibits proliferation and migration of VSMCs processes that contribute to the development of atherosclerotic plaques 29 . We previously reported that liraglutide treatment increases NO levels in plasma and phosphorylated endothelial NO synthase levels in the aorta 18 . In addition, liraglutide treatment suppresses peripheral arterial remodeling in mouse models, and this effect is completely abolished by inhibiting NO synthase.…”

Section: Discussionmentioning

confidence: 96%

“…Blood pressure and pulse rate were measured using the tail-cuff method, as previously described Model MK-2000ST ; Muromachi Kikai, Tokyo, Japan 18 .…”

Section: Blood Pressure and Pulse Rate Measurementsmentioning

confidence: 99%

“…Total RNA was extracted from the brachiocephalic arteries using Isogen Nippon Gene, Tokyo, Japan , and used to synthesize cDNA using ReverTra Ace Toyobo, Osaka, Japan as previously described 18 . Gene expression was assessed by real-time reverse transcription PCR using the TaqMan gene expression assay and a sequence detection system StepOne ; Life Technologies Japan, Tokyo, Japan .…”

Section: Assessment Of Gene Expressionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of Vascular Endothelial Cells in the Anti-atherogenic Effects of Liraglutide in Diabetic Apolipoprotein E-null Mice

Koshibu

Mori

Kushima

et al. 2019

Showa Univ J Med Sci

Self Cite

View full text Add to dashboard Cite

Glucagon-like peptide 1 receptor agonists GLP-1RAs have been shown to exert anti-atherosclerotic effects via multiple mechanisms on different types of cells. However, it is unclear which of these mechanisms are crucial. We investigated the role of vascular endothelial cells VECs in the anti-atherogenic effects of the GLP-1RA liraglutide in a mouse model of atherosclerosis. Streptozotocin-induced diabetic apolipoprotein E-null mice were randomly assigned to treatment with either vehicle saline or liraglutide 107 nmol/kg/day , and were subjected to femoral artery wire injury to remove VECs. After 4 weeks, vessel samples were collected for analysis. Streptozotocin-injected mice had fasting plasma glucose levels of 300 mg/dl and hemoglobin A1c levels of 9 , indicating that the injections had induced severe hyperglycemia. However, there were no differences in metabolic characteristics such as levels of hemoglobin A1c, fasting plasma glucose, total cholesterol, and triglycerides between the vehicle and liraglutide groups. Analysis of atherosclerotic plaque formation revealed that liraglutide treatment signi cantly suppressed plaque formation in the aorta. In addition, liraglutide treatment reduced plaque volume and intra-plaque macrophage accumulation at the aortic sinus. Furthermore, liraglutide treatment suppressed vascular expression of pro-in ammatory cytokines. In uninjured femoral arteries, no plaques were observed ; however, severe plaque formation occurred in femoral arteries that had been injured by wire insertion to remove VECs. Unlike in the uninjured aorta, liraglutide treatment did not affect plaque volume or arterial remodeling intimal and medial thinning, and arterial dilation in wire-injured femoral arteries. Of the various cells that liraglutide affects, VECs play a central role in liraglutide s anti-atherogenic effects in diabetic mice.

show abstract

“…However, these drugs can also directly target vascular cells finally resulting in reduced atherogenesis. Preclinical data suggested that liraglutide can suppress restenosis via endothelial nitric oxide release in a mouse model of femoral artery wire injury in presence of severe hyperglycaemia . In addition, liraglutide decreased the progression of atherogenesis, contributing to plaque stability and endothelial function both in preclinical and clinical studies .…”

Section: Direct Evidences For New Anti‐diabetic Drugs Against CV Diseasementioning

confidence: 99%

Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists

et al. 2019

View full text Add to dashboard Cite

Bonaventura A, ). Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT-2 inhibitors and GLP-1 receptor agonists (Review). J Intern Med 2019; 286: 16-31.Patients with type 2 diabetes mellitus (T2D) present an increased risk for cardiovascular (CV) complications. In addition to improvement in glycaemic control, glucose-lowering therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-dependent glucose cotransporter (SGLT)-2 inhibitors, have been shown to significantly reduce CV events. In 2008, the US Food and Drug Administration mandated that all new glucose-lowering drugs undergo CV outcomes trials (CVOTs) to determine their CV safety. These trials have largely demonstrated no major CV safety concerns. Most notably, the GLP-1RAs and SGLT-2 inhibitors have been found to be not only safe, but also cardioprotective compared to placebo. The SGLT-2 inhibitors have opened a new perspective for clinicians treating patients with T2D and established CV disease in light of their 'pleiotropic' effects, specifically on heart failure, while GLP-1RAs seem to present more favourable effects on atherosclerotic events. In this review, we discuss the role of GLP-1RAs and SGLT-2 inhibitors to reduce CV risk in T2D patients and suggest an individualized therapeutic approach in this population based on the presence of metabolic and CV comorbidities.

show abstract

The role of endothelial nitric oxide in the anti-restenotic effects of liraglutide in a mouse model of restenosis

Cited by 41 publications

References 58 publications

RETRACTED ARTICLE: GLP-1 receptor agonist lixisenatide protects against high free fatty acids-induced oxidative stress and inflammatory response

RETRACTED ARTICLE: GLP-1 receptor agonist lixisenatide protects against high free fatty acids-induced oxidative stress and inflammatory response

Involvement of Vascular Endothelial Cells in the Anti-atherogenic Effects of Liraglutide in Diabetic Apolipoprotein E-null Mice

Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists

Contact Info

Product

Resources

About