Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiac Disorders

Wroge, Jamie; Williams, Nancy Toedter

doi:10.1177/1060028016663218

Cited by 14 publications

(14 citation statements)

References 47 publications

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“…Previous studies have demonstrated that GLP-1 infusion has beneficial effects on cardiovascular function in conjunction with its anti-diabetic properties by improving EF, NYHA functional status and peak exercise oxygen consumption (Sokos, et al, 2006;Wroge & Williams, 2016). GLP-1 analogue infusion following AMI has also been shown to have cardioprotective benefits, likely from activation of the PI3K-Akt pathway and through increasing cytosolic cAMP, which inhibit the mitochondrial permeability transition pore (mPTP), and increase myocardial expression of PPAR-β/δ, nuclear factor related factor 2 (Nrf-2), and haemoxygenase-1 (HO-1; Giblett, et al, 2016).…”

Section: Glp-1 Analoguesmentioning

confidence: 99%

“…Liraglutide therapy has also been shown to increase plasma ANP levels due to atrial GLP-1 receptor activation, which has potent natriuretic and antihypertensive effects via increased vascular cGMP (Kim, et al, 2013). In both rat and mouse models of HF, exenatide treatment delayed the progression towards HF and increased survival rates following AMI (Wroge & Williams, 2016).…”

Section: Glp-1 Analoguesmentioning

confidence: 99%

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Cardiac metabolism — A promising therapeutic target for heart failure

Noordali

Loudon

Frenneaux

et al. 2018

Pharmacology & Therapeutics

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Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants.Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed.

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Section: Glp-1 Analoguesmentioning

confidence: 99%

Section: Glp-1 Analoguesmentioning

confidence: 99%

Cardiac metabolism — A promising therapeutic target for heart failure

Noordali

Loudon

Frenneaux

et al. 2018

Pharmacology & Therapeutics

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“…Interestingly, besides regulation of glucose homeostasis, GLP-1 mimetic peptides have also been shown to exert cardioprotective effects in cardiovascular-related death, non-fatal MI, and non-fatal stroke (Advani et al, 2013; Wroge and Williams, 2016). …”

Section: Incretin Mimeticsmentioning

confidence: 99%

The Potential Therapeutic Application of Peptides and Peptidomimetics in Cardiovascular Disease

et al. 2017

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Cardiovascular disease (CVD) remains a leading cause of mortality and morbidity worldwide. Numerous therapies are currently under investigation to improve pathological cardiovascular complications, but yet, there have been very few new medications approved for intervention/treatment. Therefore, new approaches to treat CVD are urgently required. Attempts to prevent vascular complications usually involve amelioration of contributing risk factors and underlying processes such as inflammation, obesity, hyperglycaemia, or hypercholesterolemia. Historically, the development of peptides as therapeutic agents has been avoided by the Pharmaceutical industry due to their low stability, size, rate of degradation, and poor delivery. However, more recently, resurgence has taken place in developing peptides and their mimetics for therapeutic intervention. As a result, increased attention has been placed upon using peptides that mimic the function of mediators involved in pathologic processes during vascular damage. This review will provide an overview on novel targets and experimental therapeutic approaches based on peptidomimetics for modulation in CVD. We aim to specifically examine apolipoprotein A-I (apoA-I) and apoE mimetic peptides and their role in cholesterol transport during atherosclerosis, suppressors of cytokine signaling (SOCS)1-derived peptides and annexin-A1 as potent inhibitors of inflammation, incretin mimetics and their function in glucose-insulin tolerance, among others. With improvements in technology and synthesis platforms the future looks promising for the development of novel peptides and mimetics for therapeutic use. However, within the area of CVD much more work is required to identify and improve our understanding of peptide structure, interaction, and function in order to select the best targets to take forward for treatment.

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“…GLP-1 is commonly studied as an anti-diabetic agent [32] with recent studies also reporting some beneficial cardioprotective effects of GLP-1 receptor agonists [33]. Incretin based therapy, especially GLP-1 receptor agonists, have become a prime therapeutic approach in treating type 2 diabetes [34].…”

Section: Discussionmentioning

confidence: 99%

Selective beneficial cardiometabolic effects of vertical sleeve gastrectomy are predominantly mediated through glucagon-like peptide (GLP-1) in Zucker diabetic fatty rats

Sricharan

Lau

Palaia

et al. 2016

Annals of Medicine &Amp; Surgery

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BackgroundGlucagon-like peptide-1 (GLP-1) level was significantly increased post Vertical Sleeve Gastrectomy (VSG), an effect believed to contribute to its beneficial cardiometabolic effects.ObjectiveTo validate the beneficial GLP-1 mediated cardiometabolic effects post VSG using GLP-1 antagonist (exendin 9-39) in Zucker diabetic fatty rats.MethodsAnimals were divided into three (n = 5) groups: (i) sham, (ii) VSG, and (iii) VSG received exendin 9–39 (GLP-1 receptor antagonist). The study was performed over 12 weeks and parameters were measured 12 weeks post-surgery.Results and discussionAs expected, fasting blood glucose and insulin levels were improved post VSG due to enhanced GLP-1 secretion. However, both fasting glucose and insulin levels were impaired in the presence of GLP-1 antagonist. Baseline total cholesterol level pre-surgery was 100±1 mg/dl which remained unchanged in the VSG group but significantly increased to 140±8 mg/dl in the presence of antagonist. Interestingly, post-surgery there was a nearly 70% reduction in triglyceride level in the VSG group compared to sham which was overcome in the presence of antagonist. Myographic studies using aortic rings showed no significant change between groups. Additionally, blood pressure and heart rate also remained unchanged in all groups. Serum bile acid and L-PGDS levels increased post VSG but significantly decreased in the presence of antagonist, suggesting a strong association with GLP-1 and a novel mechanism of action.ConclusionEnhanced GLP-1 secretion post VSG imparted beneficial cardiometabolic effects on blood glucose, insulin, total cholesterol, triglyceride, bile acids and L-PGDS levels which were abated in the presence of GLP-1 antagonist.

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Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiac Disorders

Cited by 14 publications

References 47 publications

Cardiac metabolism — A promising therapeutic target for heart failure

Cardiac metabolism — A promising therapeutic target for heart failure

The Potential Therapeutic Application of Peptides and Peptidomimetics in Cardiovascular Disease

Selective beneficial cardiometabolic effects of vertical sleeve gastrectomy are predominantly mediated through glucagon-like peptide (GLP-1) in Zucker diabetic fatty rats

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