Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes

Luna-Marco, Clara; de Marañon, Arantxa M.; Hermo-Argibay, Alberto; Rodriguez-Hernandez, Yohaly; Hermenejildo, Jonathan; Fernandez-Reyes, Meylin; Apostolova, Nadezda; Vila, Jose; Sola, Eva; Morillas, Carlos; Rovira-Llopis, Susana; Rocha, Milagros; Victor, Victor M.

doi:10.1016/j.redox.2023.102849

Cited by 22 publications

(11 citation statements)

References 47 publications

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“…By downregulating certain inflammatory factors and adhesion molecules in the artery wall, GLP-1RAs prevent the concentration of monocytes and macrophages, leading to inflammation inhibition in the endothelial cells and achieving an anti-AS effect. Given the importance of inflammation in the development of AS, the therapeutic concept of reducing inflammation as a strategy to prevent AS and its complications has gained increasing attention, with research on GLP-1RAs contributing significantly to advancing this concept ( Luna-Marco et al, 2023 ).…”

Section: Molecular Mechanism Of Anti-as By Glp-1rasmentioning

confidence: 99%

“…Impairment of the mitochondrial respiratory chain or high proton motive force increases ROS production. In contrast, GLP-1RAs can attenuate oxidative stress, improve respiratory chain activity, increase ATP production, and delay the progression of AS by protecting mitochondrial function ( Luna-Marco et al, 2023 ). The generation of ROS and the preservation of cellular homeostasis depend heavily on mitophagy, a process driven by the phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) ( Guan et al, 2023 ).…”

Section: Molecular Mechanism Of Anti-as By Glp-1rasmentioning

confidence: 99%

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Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Wang,

Ding,

Cheng

et al. 2024

Front. Pharmacol.

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Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of cardiovascular mortality and is increasingly prevalent in our population. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can safely and effectively lower glucose levels while concurrently managing the full spectrum of ASCVD risk factors and improving patients’ long-term prognosis. Several cardiovascular outcome trials (CVOTs) have been carried out to further investigate the cardiovascular benefits of GLP-1RAs. Analyzing data from CVOTs can provide insights into the pathophysiologic mechanisms by which GLP-1RAs are linked to ASCVD and define the use of GLP-1RAs in clinical practice. Here, we discussed various mechanisms hypothesized in previous animal and preclinical human studies, including blockade of the production of adhesion molecules and inflammatory factors, induction of endothelial cells’ synthesis of nitric oxide, protection of mitochondrial function and restriction of oxidative stress, suppression of NOD-like receptor thermal protein domain associated protein three inflammasome, reduction of foam cell formation and macrophage inflammation, and amelioration of vascular smooth muscle cell dysfunction, to help explain the cardiovascular benefits of GLP-1RAs in CVOTs. This paper provides an overview of the clinical research, molecular processes, and possible therapeutic applications of GLP-1RAs in ASCVD, while also addressing current limitations in the literature and suggesting future research directions.

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Section: Molecular Mechanism Of Anti-as By Glp-1rasmentioning

confidence: 99%

Section: Molecular Mechanism Of Anti-as By Glp-1rasmentioning

confidence: 99%

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Wang,

Ding,

Cheng

et al. 2024

Front. Pharmacol.

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“…Indeed, GLP1-RAs decrease reactive oxygen species (ROS) production in endothelial cells and cardiomyocytes and reduce circulating levels of 8-iso prostaglandin and the accumulation of monocytes/macrophages in the vascular wall. GLP1-RAs also inhibit the expression of adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1), E-selectin, and intercellular adhesion molecule-1 (ICAM-1) and their transformation in foam cells, slowing the process of atherosclerotic plaque formation [ 65 , 66 ]. Moreover, GLP1-RAs lead to endothelial-dependent vasorelaxation, inducing the expression of endothelial NO synthase (eNOS) while reducing endothelin levels [ 67 ].…”

Section: Mechanisms Of Glp1-ra Benefits In Cardiovascular Diseasesmentioning

confidence: 99%

Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

Gallo,

Volpe

2024

IJMS

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Different multifactorial pathophysiological processes are involved in the development of heart failure (HF), including neurohormonal dysfunction, the hypertrophy of cardiomyocytes, interstitial fibrosis, microvascular endothelial inflammation, pro-thrombotic states, oxidative stress, decreased nitric oxide (NO) bioavailability, energetic dysfunction, epicardial coronary artery lesions, coronary microvascular rarefaction and, finally, cardiac remodeling. While different pharmacological strategies have shown significant cardiovascular benefits in HF with reduced ejection fraction (HFrEF), there is a residual unmet need to fill the gap in terms of knowledge of mechanisms and efficacy in the outcomes of neurohormonal agents in HF with preserved ejection fraction (HFpEF). Recently, type-2 sodium–glucose transporter inhibitors (SGLT2i) have been shown to contribute to a significant reduction in the composite outcome of HF hospitalizations and cardiovascular mortality across the entire spectrum of ejection fraction. Moreover, glucagon-like peptide-1 receptor agonists (GLP1-RA) have demonstrated significant benefits in patients with high cardiovascular risk, excess body weight or obesity and HF, in particular HFpEF. In this review, we will discuss the biological pathways potentially involved in the action of SGLT2i and GLP1-RA, which may explain their effective roles in the treatment of HF, as well as the potential implications of the use of these agents, also in combination therapies with neurohormonal agents, in the clinical practice.

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“…GLP-1RAs have shown clinical benefits, including improved insulin sensitivity, improved metabolic profiles and reduced cardiovascular events. 16 GLP-1RAs lead to significant weight loss, 17 lower inflammatory markers 18 and reduced hepatic steatosis and lipotoxicity. 19 Clinical evidence of the safety and effectiveness of GLP-1RAs medications in cirrhosis is lacking, as the cirrhotic population is generally excluded from Randomised Clinical Trials (RCTs).…”

Section: Introductionmentioning

confidence: 99%

“…GLP‐1RAs have shown clinical benefits, including improved insulin sensitivity, improved metabolic profiles and reduced cardiovascular events 16 . GLP‐1RAs lead to significant weight loss, 17 lower inflammatory markers 18 and reduced hepatic steatosis and lipotoxicity 19 …”

Section: Introductionmentioning

confidence: 99%

Impacts of glucagon‐like peptide‐1 receptor agonists on the risk of adverse liver outcomes in patients with metabolic dysfunction‐associated steatotic liver disease cirrhosis and type 2 diabetes

Elsaid,

Li,

Firkins

et al. 2024

Aliment Pharmacol Ther

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SummaryBackground/AimsWe examined the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) initiation on long‐term Adverse Liver Outcomes (ALO) in patients with Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) cirrhosis and type 2 diabetes using real‐world data from the MarketScan database.MethodsWe conducted a retrospective cohort study of patients with MASLD cirrhosis and type 2 diabetes between 2012 and 2020. Cox proportional hazard models examine the association between GLP‐1RAs initiation, modelled as time‐dependent, and the risk of ALO, a composite endpoint defined by the first occurrence of hepatic decompensation(s), portal hypertension, hepatocellular carcinoma (HCC) or liver transplantation (LT). We used Overlap Propensity Score Weighting (OPSW) to account for confounding. The study included 459 GLP‐1RAs and 4837 non‐GLP‐1RAs patients.ResultsThe non‐GLP‐1RAs patients presented with 1411 (29%) ALO over 7431.7 person years, while GLP‐1RAs patients had 32 (7%) ALO over 586.6 person years – risk rate difference 13.5 (95% CI: 11.4–15.7) per 100 person‐years. The OPSW‐adjusted risk of ALO was reduced by 36% (hazard ratio [HR]: 0.64; 95% CI: 0.54–0.76) in patients with vs. without GLP‐1RAs initiation. GLP‐1RAs initiation was associated with significant reductions in the adjusted risk of hepatic decompensation (HR: 0.74; 95% CI: 0.61–0.88), portal hypertension (HR: 0.73; 95% CI: 0.60–0.88), HCC (HR: 0.37; 95% CI: 0.20–0.63) and LT (HR: 0.24; 95% CI: 0.12–0.43).ConclusionThe use of GLP‐1RAs was associated with significant risk reductions in long‐term adverse liver outcomes, including hepatic decompensation, portal hypertension, HCC and LT, in MASLD cirrhosis patients with type 2 diabetes.

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Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes

Cited by 22 publications

References 47 publications

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Glucagon-like peptide-1 receptor agonists: new strategies and therapeutic targets to treat atherosclerotic cardiovascular disease

Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

Impacts of glucagon‐like peptide‐1 receptor agonists on the risk of adverse liver outcomes in patients with metabolic dysfunction‐associated steatotic liver disease cirrhosis and type 2 diabetes

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