Effects of incretin agonists on endothelial nitric oxide synthase expression and nitric oxide synthesis in human coronary artery endothelial cells exposed to TNFα and glycated albumin

Garczorz, Wojciech; Francuz, Tomasz; Siemianowicz, Krzysztof; Kosowska, Agnieszka; Kłych, Agnieszka; Aghdam, Mohammad Reza F.; Jagoda, Krystyna

doi:10.1016/j.pharep.2014.08.007

Cited by 11 publications

(7 citation statements)

References 37 publications

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“…84 We observed that GLP-1RAs are associated with a reduction in TNFα; elevated levels of TNFα have been implicated in endothelial dysfunction in laboratory experiments. 85 Adiponectin has a complex relationship with cardiovascular risk. Meta-analysis of observational studies including people with and without T2DM did not show a benefit of higher adiponectin levels on cardiovascular disease risk.…”

Section: Discussionmentioning

confidence: 99%

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Bray

Foster‐Davies

Salem

et al. 2021

Diabetes Obesity Metabolism

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Aim: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes.Methods: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation: C-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG). Results: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m 2 and diabetes duration 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference À0.54 mg/L [À0.75, À0.34]; standard mean difference [SMD] À0.39 [À0.62, À0.15]; SMD À0.84 [À1.61, À0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. Conclusions: There is strong evidence supporting clinically relevant antiinflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs. * Jonathan J. H. Bray and Harri Foster-Davies are co-first authors.

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Section: Discussionmentioning

confidence: 99%

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Bray

Foster‐Davies

Salem

et al. 2021

Diabetes Obesity Metabolism

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“…Human ovarian cancer cell lines, SKOV-3 and CAOV-3 (ATCC), were cultured in DMEM (Sigma) or McCoy (Sigma) medium, respectively, with 1% antibiotics (Sigma) and 10% FBS (Sigma) at 37°C in 5% CO 2 humidified incubator. Human Iliac artery endothelial cells and human aortic endothelial cells (Lonza, Basel, Switzerland) were cultured in EBM-2 culture medium as previously described ( 20 ). Three ovarian tumor cell lines were isolated de novo from anonymous patients undergoing surgical removal of the ovaries due to ovarian cancer with patients’ consent.…”

Section: Methodsmentioning

confidence: 99%

Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells

Kosowska

Gallego‐Colon

Garczorz

et al. 2017

Endocrine Connections

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Diabetes and cancer are prevalent diseases whose incidence is increasing globally. Diabetic women have a moderate risk increase in ovarian cancer, suggested to be due to an interaction between these two disorders. Furthermore, patients manifesting both diseases have associated worse prognosis, reduced survival and shorter relapse-free survival. According to current recommendations, incretin drugs such as Exenatide, a synthetic analog of Exendin-4, and Liraglutide are used as therapy for the type 2 diabetes (T2D). We studied the effects of GLP-1 and Exendin-4 on migration, apoptosis and metalloproteinase production in two human ovarian cancer cells (SKOV-3 and CAOV-3). Exendin-4 inhibited migration and promoted apoptosis through caspase 3/7 activation. Exendin-4 also modulated the expression of key metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). Vascular endothelial cells, which contribute to the formation and progression of metastasis, were also analyzed. TNF-α-stimulated endothelial cells from iliac artery after Exendin-4 treatment showed reduced production of adhesion molecules (ICAM-1 and VCAM-1). Additionally, incretin treatment inhibited activation of apoptosis in TNF-α-stimulated endothelial cells. In the same experiment, MMPs (MMP-1 and MMP-9), which are relevant for tumor development, were also reduced. Our study demonstrated that incretin drugs may reduce cancer cell proliferation and dissemination potential, hence limiting the risk of metastasis in epithelial ovarian cancer.

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“…Intracellular NO was analyzed using the NO-specific fluorescent dye DAF-FM DA (Life Technologies; Garczorz et al , 2015). Briefly, cells were loaded with 5 μM DAF-FM DA at 37°C for 30 min in the dark.…”

Section: Methodsmentioning

confidence: 99%

The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS–Ser-633 phosphorylation and nitric oxide production

Kong

Chen

et al. 2016

MBoC

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Effects of incretin agonists on endothelial nitric oxide synthase expression and nitric oxide synthesis in human coronary artery endothelial cells exposed to TNFα and glycated albumin

Abstract: TNFα and GA decrease production of NO in HCAEC, presumably by inducing reactive oxygen species or eNOS uncoupling. Incretin agonists in tested concentrations in the presence of l-arginine were not able to reverse this effect and instead led to a further reduction in NO production.

Cited by 11 publications

References 37 publications

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Glucagon‐like peptide‐1 receptor agonists improve biomarkers of inflammation and oxidative stress: A systematic review and meta‐analysis of randomised controlled trials

Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells

The role of HYAL2 in LSS-induced glycocalyx impairment and the PKA-mediated decrease in eNOS–Ser-633 phosphorylation and nitric oxide production

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