Semaglutide attenuates excessive exercise-induced myocardial injury through inhibiting oxidative stress and inflammation in rats

Liu, Qiang; Tuo, Xinling; Li, Biyou; Deng, Zuhu; Qiu, Yonghong; Xie, Hui

doi:10.1016/j.lfs.2020.117531

Cited by 31 publications

(34 citation statements)

References 23 publications

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“…GLP-1RAs have the potential to inhibit cardiac inflammation via retarding the production of pyroptotic cytokines, caspase-1 and the AMPK-thioredoxin interacting protein (TXNIP) pathway in high-fat diet-fed rats [80]. Specifically, GLP-1RAs exert protective effects on exercise-induced cardiomyopathy via increasing autophagy, reducing inflammation-related proteins and ROS generation via restoring the expression of catalase and manganese superoxide dismutase (MnSOD) [81].…”

Section: Effects Of Glp-1ras On Cardiomyopathymentioning

confidence: 99%

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

120

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Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.

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Section: Effects Of Glp-1ras On Cardiomyopathymentioning

confidence: 99%

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

120

View full text Add to dashboard Cite

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“…GLP-1 receptor stimulation appears to attenuate these processes in preclinical models and human studies in various ways. GLP-1 receptor stimulation (e.g., through GLP-1 (24-27), exenatide (28), liraglutide (26,(29)(30)(31)(32), or semaglutide (33) prevents ROS and reduces vascular oxidative stress. The secretion of adhesion molecules including VCAM-1, MCP-1, ICAM-1, and E-selectin is also reduced by GLP-1 (34), exenatide (34)(35)(36), liraglutide (37), and dulaglutide (22).…”

Section: Mechanisms For the Cardiovascular Benefits Of Glp-1rasmentioning

confidence: 99%

Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6

Nauck

2021

Front. Endocrinol.

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To exclude an excess risk of cardiovascular (CV) events, CV outcomes trials (CVOTs) have assessed the effects of new glucose-lowering therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients with type 2 diabetes and established CV disease or CV risk factors. The CV safety of semaglutide vs. placebo, when added to standard care, was evaluated in the SUSTAIN 6 trial for the formulation administered once-weekly subcutaneously and in PIONEER 6 for the new once-daily oral formulation. In SUSTAIN 6 and PIONEER 6, both powered to demonstrate noninferiority (upper 95% confidence interval [CI] of the hazard ratio [HR] <1.8), there were fewer first major adverse CV events with semaglutide vs. placebo, with HRs of 0.74 (95% CI 0.58–0.95) and 0.79 (0.57–1.11), respectively. In SUSTAIN 6, the results were significant for noninferiority and superiority, although the latter was not prespecified. Surprisingly, CV and all-cause mortality were significantly reduced by oral semaglutide in PIONEER 6. The ongoing SOUL CVOT will further inform about CV outcomes with oral semaglutide vs. placebo (NCT03914326). Findings from SUSTAIN 6 and PIONEER 6 fall within the spectrum reported with other GLP-1RA CVOTs: noninferiority vs. placebo for major CV events was seen with lixisenatide and exenatide extended-release, while superiority was demonstrated with liraglutide, albiglutide, and dulaglutide. Beneficial outcomes have been recognized in international guidelines, which recommend subcutaneous liraglutide, semaglutide, and dulaglutide to reduce the risk of CV events in high-risk patients. Both indirect mechanisms via risk factor modification and direct effects via GLP-1 receptors in the CV system have been proposed to be responsible for CV event reductions. The exact mechanism(s) remains to be characterized, but appears to be mainly linked to anti-atherosclerotic effects. Further research is needed to elucidate the relevant mechanisms for CV benefits of GLP-1RAs.

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“…Treatment with oral semaglutide led to a greater reduction in the inflammatory marker C-reactive protein compared to the sodium-glucose co-transporter-2 inhibitor (SGLT-2i) empagliflozin, without any difference in reduction in body weight between compounds ( 28 ). Findings from animal studies suggest that GLP-1R activation may promote anti-arteriosclerotic mechanisms inducing plaque stabilisation and preventing plaque progression ( 29 , 30 , 31 , 32 , 33 ). Interestingly, GLP-1RA treatment is associated with small reductions in systolic blood pressure, which seem independent of GLP-1RA-induced weight loss ( 34 ).…”

Section: Effects Of Glp-1ras In Type 2 Diabetesmentioning

confidence: 99%

“…These results are in line with previous findings on the effect of GLP-1RAs on NASH ( 53 , 54 ). As the GLP-1R is not expressed on human hepatocytes, the GLP-1RA-mediated effects on fatty liver are probably indirectly mediated through GLP-1RA-induced weight loss and ensuing improvement in insulin resistance, and, potentially, anti-inflammatory effects associated with GLP-1RA treatment ( 29 ). Integrating the actions of GLP-1 with other receptor agonists is emerging as a potential new drug class with pharmaceutical potential in treating, for example, liver diseases.…”

Section: Treatment With Glp-1ras For Other Indications Than T2d and Obesitymentioning

confidence: 99%

How glucagon-like peptide 1 receptor agonists work

Andreasen

Andersen

Knop

et al. 2021

Endocrine Connections

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Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

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Semaglutide attenuates excessive exercise-induced myocardial injury through inhibiting oxidative stress and inflammation in rats

Cited by 31 publications

References 23 publications

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6

How glucagon-like peptide 1 receptor agonists work

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