The Glp-1 Analog Liraglutide Protects Against Angiotensin II and Pressure Overload-Induced Cardiac Hypertrophy via PI3K/Akt1 and AMPKa Signaling

Li, Ran; Shan, Yingguang; Wang, Xi; Wang, Xule; Wang, Fang

doi:10.3389/fphar.2019.00537

Cited by 33 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…and AKT2, but not AKT3 were reported to inhibit fibrogenesis in hepatocytes and HSC [39]. Besides, previous studies had revealed that the PI3K/AKT signaling pathway was associated with hypertrophy and fibrosis in different tissues such as cardiac hypertrophy [40] and liver fibrosis [18]. Moreover, our data also found that AA treatment upregulated the phosphorylation of AMPK.…”

Section: Discussionsupporting

confidence: 61%

Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

Liu

Yang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background Osteoarthritis (OA), the most common joint disorder, is characterized by a progressive degradation of articular cartilage. Increasing evidence suggests that OA is closely associated with cartilage pathologies including chondrocyte hypertrophy and fibrosis.Methods In this study, we showed that Asiatic acid (AA) treatment reduced chondrocyte hypertrophy and fibrosis. First, the cytotoxicity of AA (0, 5, 10, and 20 μM) to chondrocytes was evaluated, and 5 μM was selected for subsequent experiments. Then, we detected the gene and protein level of chondrocyte hypertrophic markers including type X collagen (COL-X), matrix metalloproteinase - 13 (MMP-13), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and chondrocyte fibrosis markers including type I collagen (COL-Ι) and alpha-smooth muscle actin (α-SMA), and chondrogenic markers including SRY-related HMG box 9 (SOX9), type II collagen (COL-II) and aggrecan (ACAN). Further, we texted the mechanism of AA on inhibiting chondrocyte hypertrophy and fibrosis. Finally, we verified the results in an anterior cruciate ligament transection (ACLT) rat OA model.Results We found that AA treatment inhibited the hypertrophic and fibrotic phenotype of chondrocytes, without affecting the chondrogenic phenotype. Moreover, we found AA treatment activated AMP-activated protein kinase (AMPK) and inhibited phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) signaling pathway in vitro. The results in an ACLT-rat OA model also indicated that AA significantly attenuated chondrocyte hypertrophy and fibrosis.Conclusion AA treatment could reduce hypertrophic and fibrotic differentiation, and maintain the chondrogenic phenotype of articular chondrocytes by targeting the AMPK/PI3K/AKT signaling pathway. Our study suggested that AA might be a prospective drug component that targets hypertrophic and fibrotic chondrocytes for OA treatment.

show abstract

Section: Discussionsupporting

confidence: 61%

Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

Liu

Yang

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…However, the mechanism by which GLP-1 agonists exert their cardiovascular protective action, especially to improve ventricular remodeling, is still unclear. It was reported that liraglutide, one kind of GLP-1 agonist, inhibited angiotensin II and pressure overload-induced cardiac remodeling by regulating PI3K/Akt1 and AMPKα signaling [63]. Wang et al [64] also found that the cardiac protection of GLP-1 agonists might be dependent on inhibition of oxidative stress through the mammalian target of rapamycin complex 1/p70 ribosomal protein S6 kinase pathway.…”

Section: Discussionmentioning

confidence: 99%

Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis

Zhang

Wang

et al. 2020

Cardiovasc Diabetol

View full text Add to dashboard Cite

Background: Although a variety of antidiabetic drugs have significant protective action on the cardiovascular system, it is still unclear which antidiabetic drugs can improve ventricular remodeling and fundamentally delay the process of heart failure. The purpose of this network meta-analysis is to compare the efficacy of sodium glucose cotransporter type 2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) agonists, metformin (MET), sulfonylurea (SU) and thiazolidinediones (TZDs) in improving left ventricular (LV) remodeling in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). Methods: We searched articles published before October 18, 2019, regardless of language or data, in 4 electronic databases: PubMed, EMBASE, Cochrane Library and Web of Science. We included randomized controlled trials in this network meta-analysis, as well as a small number of cohort studies. The differences in the mean changes in left ventricular echocardiographic parameters between the treatment group and control group were evaluated. Results: The difference in the mean change in LV ejection fraction (LVEF) between GLP-1 agonists and placebo in treatment effect was greater than zero (MD = 2.04% [0.64%, 3.43%]); similar results were observed for the difference in the mean change in LV end-diastolic diameter (LVEDD) between SGLT-2 inhibitors and placebo (MD = − 3.3 mm [5.31, − 5.29]), the difference in the mean change in LV end-systolic volume (LVESV) between GLP-1 agonists and placebo (MD = − 4.39 ml [− 8.09, − 0.7]); the difference in the mean change in E/e′ between GLP-1 agonists and placebo (MD = − 1.05[− 1.78, − 0.32]); and the difference in the mean change in E/e′ between SGLT-2 inhibitors and placebo (MD = − 1.91[− 3.39, − 0.43]). Conclusions: GLP-1 agonists are more significantly associated with improved LVEF, LVESV and E/e′, SGLT-2 inhibitors are more significantly associated with improved LVEDD and E/e′, and DPP-4 inhibitors are more strongly associated with a negative impact on LV end-diastolic volume (LVEDV) than are placebos. SGLT-2 inhibitors are superior to other drugs in pairwise comparisons.

show abstract

“…43,44 Liraglutide also inhibits cardiac remodeling via regulating PI3K/Akt1 and AMPKα signaling. 45 Thus, the effects of liraglutide on myocardial fibrosis are multifactorial and partially related to activation of adenosine 5‘-monophosphate (AMP)-activated protein kinase-α (AMPKα) signaling.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide Attenuates Myocardial Fibrosis via Inhibition of AT1R-Mediated ROS Production in Hypertensive Mice

Chen

Yang

Wang

et al. 2020

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

Background/Aims: Glucagon-like peptide-1 receptor agonist liraglutide has been reported to exert cardioprotective effects, but its effect on cardiac fibrosis remains controversial. The aim of this study was to investigate the effects of liraglutide on cardiac fibrosis and potential mechanisms. Methods: C57BL/6 mice (3-month old) were randomly divided into control, hypertension, and hypertension + liraglutide groups. The hypertensive state was created by infusion of Ang II (100 ng/kg·min) for 4 weeks through subcutaneously implanted osmotic pumps. The control mice were infused with saline. Mice were also given vehicle or liraglutide (400 μg/kg·day). Blood pressure (BP), blood sugar, myocardial fibrosis, AT1R expression, and reactive oxygen species (ROS) levels were measured. To further elucidate the mechanisms of fibrosis, mouse cardiac fibroblasts were isolated and treated with liraglutide (300 nM/L) or losartan (10 μM) for 3 hours, followed by Ang II (10−7 M) for additional 12 hours. Reactive oxygen species production and expressions of collagen-1 and -3 were measured. Results: Liraglutide reduced BP and blood sugar but did not affect the body weight of the hypertensive mice. Liraglutide also inhibited collagen accumulation, AT1R expression, and ROS generation in the hearts of the hypertensive mice. In in vitro studies, pretreatment with liraglutide and losartan (as control) markedly inhibited Ang II-induced ROS production and collagen expression in the cultured cardiac fibroblasts. Conclusion: Liraglutide reduces myocardial fibrosis in the hypertensive mice, which appears to be dependent on at least in part inhibition of ROS production.

show abstract

The Glp-1 Analog Liraglutide Protects Against Angiotensin II and Pressure Overload-Induced Cardiac Hypertrophy via PI3K/Akt1 and AMPKa Signaling

Cited by 33 publications

References 38 publications

Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

Effects of antidiabetic drugs on left ventricular function/dysfunction: a systematic review and network meta-analysis

Liraglutide Attenuates Myocardial Fibrosis via Inhibition of AT1R-Mediated ROS Production in Hypertensive Mice

Contact Info

Product

Resources

About