GLP-1 Improves Diastolic Function and Survival in Heart Failure with Preserved Ejection Fraction

Nguyễn, Tiến Dũng; Shingu, Yasushige; Amorim, Paulo A.; Schenkl, C.; Schwarzer, Michael; Doenst, Torsten

doi:10.1007/s12265-018-9795-z

Cited by 30 publications

(23 citation statements)

References 43 publications

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“…GLP-1 receptors are present in cardiac tissue (23) . In a rat model of HFpEF, GLP-1 infusions directly led to improved diastolic function and improved survivorship (24) . Therefore, along with increased cardiac SERCA2a, it is possible that postprandial GLP-1 is also contributing to the decrease in IVRT and E/e' that is observed in the SG animals.…”

Section: Discussionmentioning

confidence: 96%

Sleeve gastrectomy in obese Wistar rats improves diastolic function and promotes cardiac recovery independent of weight loss

Hayes

Patz

Corbett

et al. 2019

Surgery for Obesity and Related Diseases

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Background: Heart failure with preserved ejection fraction (HFpEF) is the most common cause of heart failure, and is characterized by impaired diastolic relaxation. Bariatric surgery significantly improves diastolic relaxation, but a mechanism beyond weight loss remains unknown. Objective: We tested the hypothesis that a sleeve gastrectomy (SG) will improve diastolic dysfunction independent of weight loss due to post-operative alterations in the entero-cardiac axis. Setting: University Research laboratory. Methods: Male, Wistar rats were fed a high-fat diet (HFD) or low-fat diet (LFD) for 10 weeks followed by SG-HFD, pair-fed sham HFD, ad-lib sham HFD, or ad-lib sham LFD (n=9-14 per group). At least 2 months postoperatively, cardiac function, meal tolerance, glucose tolerance, and cardiac gene expression were compared between groups. Results: Only the SG cohort showed significant improvements in post-operative diastolic relaxation (isovolumetric relaxation time pre: 14.7 ± 2.3 msec, post: 11.2 ± 1.8 msec, p<0.001). SG significantly increased active glucagon-like peptide-1 (p=0.03). Compared to pair-fed sham HFD rats, SG-HFD rats had significantly altered mRNA cardiac gene expression including sarco/ endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) (p<0.001).

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Section: Discussionmentioning

confidence: 96%

Sleeve gastrectomy in obese Wistar rats improves diastolic function and promotes cardiac recovery independent of weight loss

Hayes

Patz

Corbett

et al. 2019

Surgery for Obesity and Related Diseases

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show abstract

“…Mounting evidence indicate that GLP-1 exert a broad range of protective effects on cardiovascular diseases, including hypertension [22], chronic heart failure [23, 24], and ischemia-reperfusion injury [25]. Not only in preconstricted systemic circulation arteries, but also in pulmonary arteries, GLP-1 receptor agonist could induce a relaxation in endothelium-dependent manner [16, 26].…”

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide-1 (GLP-1) mediates the protective effects of dipeptidyl peptidase IV inhibition on pulmonary hypertension

Wang

et al. 2019

J Biomed Sci

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BackgroundPulmonary hypertension (PH) is a progressive disease leading to death ultimately. Our recently published data demonstrated that inhibiting dipeptidyl peptidase IV (DPP-4) alleviated pulmonary vascular remodeling in experimental PH. However, whether glucagon-like peptide-1 (GLP-1) mediated the protective effect of DPP-4 inhibition (DPP-4i) on PH is unclear.ResultsIn the present study, GLP-1 receptor antagonist (exendin-3) abolished the protective effects of DPP-4 inhibitor (sitagliptin) on right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling (PVR) in monocrotaline (MCT, 60 mg/kg)-induced PH in rat. Notably, activation of GLP-1 receptor by GLP-1 analogue liraglutide directly attenuated RVSP and PVR in MCT-induced PH, as well as bleomycin- and chronic hypoxia-induced PH. Moreover, liraglutide potently inhibited MCT-induced inflammation and suppressed MCT-induced down-regulation of vascular endothelial marker (VE-cadherin and vWF) in lung. In vitro studies showed liraglutide reversed TGF-β1 (5 ng/ml) combining IL-1β (5 ng/ml) induced endothelial-mesenchymal transition (EndMT) in human umbilical vein endothelial cells (HUVECs), which could be abolished by GLP-1 receptor antagonist (exendin-3). Furtermore, liraglutide suppressed TGF-β1-IL-1β-induced phosphorylation of both Smad3 and ERK1/2.ConclusionsOur data suggest that GLP-1 mediated the protective effects of DPP-4i on pulmonary vascular and RV remodeling in experimental PH, which may be attributed to the inhibitory effect on EndMT.

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“…DDP-4 inhibitors were reported to prevent cardiac diastolic dysfunction [47], ameliorate cardiac function in pressure overload heart failure [48], and attenuate the annual exacerbation of diastolic dysfunction [49]. Multiple lines of evidence have demonstrated the beneficial effects of GLP-1 RAs on heart function [50–52]. Meta-analyses have also suggested that these drugs can improve LVEF in patients with or without HF [53, 54].…”

Section: Discussionmentioning

confidence: 99%

Targeting the DPP-4-GLP-1 pathway improves exercise tolerance in heart failure patients: a systematic review and meta-analysis

Chen

Huang

Zeng

et al. 2019

BMC Cardiovasc Disord

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BackgroundThe most significant manifestation of heart failure is exercise intolerance. This systematic review and meta-analysis was performed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide 1 receptor agonists (GLP-1 RAs), widely used anti-diabetic drugs, could improve exercise tolerance in heart failure patients with or without type 2 diabetes mellitus.MethodsAn electronic search of PubMed, EMBASE and the Cochrane Library was carried out through March 8th, 2019, for eligible trials. Only randomized controlled studies were included. The primary outcome was exercise tolerance [6-min walk test (6MWT) and peak O2 consumption], and the secondary outcomes included quality of life (QoL), adverse events (AEs) and all-cause death.ResultAfter the literature was screened by two reviewers independently, four trials (659 patients) conducted with heart failure patients with or without type 2 diabetes met the eligibility criteria. The results suggested that targeting the DPP-4-GLP-1 pathway can improve exercise tolerance in heart failure patients [MD 24.88 (95% CI 5.45, 44.31), P = 0.01] without decreasing QoL [SMD -0.51 (95% CI -1.13, 0.10), P = 0.10]; additionally, targeting the DPP-4-GLP-1 pathway did not show signs of increasing the incidence of serious AEs or mortality.ConclusionOur results suggest that DPP-4 inhibitors or GLP-1 RAs improve exercise tolerance in heart failure patients. Although the use of these drugs for heart failure has not been approved by any organization, they may be a better choice for type 2 diabetes mellitus patients with heart failure. Furthermore, as this pathway contributes to the improvement of exercise tolerance, it may be worth further investigation in exercise-intolerant patients with other diseases.

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GLP-1 Improves Diastolic Function and Survival in Heart Failure with Preserved Ejection Fraction

Cited by 30 publications

References 43 publications

Sleeve gastrectomy in obese Wistar rats improves diastolic function and promotes cardiac recovery independent of weight loss

Sleeve gastrectomy in obese Wistar rats improves diastolic function and promotes cardiac recovery independent of weight loss

Glucagon-like peptide-1 (GLP-1) mediates the protective effects of dipeptidyl peptidase IV inhibition on pulmonary hypertension

Targeting the DPP-4-GLP-1 pathway improves exercise tolerance in heart failure patients: a systematic review and meta-analysis

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