MFGE8 attenuates Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway

Ge, Zhuowang; Chen, Youming; Wang, Bo; Zhang, Xuan; Yan, Yilin; Zhou, Lei; Zhang, Yachen; Xie, Ying

doi:10.1016/j.yjmcc.2020.01.001

Cited by 37 publications

(32 citation statements)

References 38 publications

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“…13 In our previous work, MFGE8 suppressed atrial fibrosis via TGF-β1/Smad2/3 pathway in an integrinβ3-dependent way and attenuated the vulnerability to atrial fibrillation. 19 Accordingly, in the present study, immunofluorescence images showed significantly decreased expression of MFGE8 in Vimentin- Figure 5A,B).…”

Section: Mfge8 Regulates Endmt Induced By Tgf-β1 Through Smad2/3 Sisupporting

confidence: 63%

“…In the aspect of cardiac fibrosis, Deng et al considered MFGE8 as an endogenous negative regulator of pathological cardiac hypertrophy, because after aortic coarctation in Mfge8 ‐knockout ( Mfge8 ‐KO) mice, substantial hypertrophic enlargement in cardiomyocytes, systolic dysfunction, and myocardial fibrosis was observed 13 . In our previous work, MFGE8 suppressed atrial fibrosis via TGF‐β1/Smad2/3 pathway in an integrinβ3‐dependent way and attenuated the vulnerability to atrial fibrillation 19 . Accordingly, in the present study, immunofluorescence images showed significantly decreased expression of MFGE8 in Vimentin‐labelled fibrosis region in the rat model of TAC‐induced cardiac fibrosis compared with that of the control group (Figure 1B).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, in recent years, a growing number of studies have emphasized the latent role of MFGE8 in organ fibrosis, such as blunting the degree of liver fibrosis in mice 17 and decreasing tissue fibrosis in mice model with lung fibrosis 18 . In our previous study, we found the protective role of MFGE8 in attenuating Ang‐II‐induced atrial fibrosis and atrial fibrillation through TGF‐β1‐Smad2/3 pathway 19 . However, how MFGE8 functions and the inner molecular mechanisms between MFGE8 and EndMT remain to be explored.…”

Section: Introductionmentioning

confidence: 92%

“…18 In our previous study, we found the protective role of MFGE8 in attenuating Ang-II-induced atrial fibrosis and atrial fibrillation through TGF-β1-Smad2/3 pathway. 19 However, how MFGE8 functions and the inner molecular mechanisms between MFGE8 and EndMT remain to be explored.…”

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confidence: 99%

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MFGE8 is down‐regulated in cardiac fibrosis and attenuates endothelial‐mesenchymal transition through Smad2/3‐Snail signalling pathway

Wang

et al. 2020

J Cellular Molecular Medi

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Heart failure (HF) is an end-stage manifestation of many cardiac diseases leading to severe functional impairment and cardiac insufficiency. The basic pathogenesis of heart failure is thought to be associated with ventricular remodelling, which is characterized by excessive cardiac fibrosis (CF). 1 Current studies indicate that myofibroblasts transformed from endothelial cells (ECs) through endothelial-mesenchymal transition (EndMT) process are responsible for cardiac fibrosis. 2,3 During EndMT, ECs experience loss of epithelia

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Section: Mfge8 Regulates Endmt Induced By Tgf-β1 Through Smad2/3 Sisupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

mentioning

confidence: 99%

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MFGE8 is down‐regulated in cardiac fibrosis and attenuates endothelial‐mesenchymal transition through Smad2/3‐Snail signalling pathway

Wang

et al. 2020

J Cellular Molecular Medi

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“…Angiotensin-II (Ang ) is a major mediator of the renin-angiotensin-aldosterone system (RAAS) and plays an essential role in the formation of atrial brosis [11,12]. Upon binding to its type 1 receptor (AT 1 -R),…”

Section: Introductionmentioning

confidence: 99%

Sacubitril/valsartan Decreased Atrial Fibrillation Susceptibility by Inhibiting Angiotensin II-induced Atrial Fibrosis through p-Smad2/3, p-JNK, and p-p38 Signaling Pathways

Zhang

et al. 2020

Preprint

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Background: Sacubitril/valsartan (SAC/VAL), combined inhibitors of angiotensin receptor (AT-R) and neprilysin receptor, prevents Angiotensin Ⅱ (AngⅡ) from binding AT1-R and blocks degradation of natriuretic peptides. Despite its efficacy in reducing ventricular fibrosis and preserving cardiac functions, which has been extensively demonstrated in myocardial infarction or pressure overload models, few studies have been conducted to determine whether SAC/VAL could attenuate atrial fibrosis and decrease atrial fibrillation (AF) susceptibility. Methods: Sprague-Dawley rats were divided into three groups after implantation of an osmotic pump preloaded with AngⅡ and received corn oil, VAL, or SAC/VAL treatment for 28 days. Electrophysiological study was performed to determine inducibility and duration of AF. Echocardiography was performed before and 28 days after osmotic mini-pump implantation to evaluate cardiac functions. Enzyme-linked immunosorbent assay was perfomed to detect the serum concentration of atrial natriuretic peptide (ANP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and AngⅡ. Masson staining was performed to determine the extent of interstitial fibrosis. Immunohistochemical, and immunofluorescence staining as well as transwell and MTT assay were also performed. Western blot analysis was perfomed to figure out how SAC/VAL exerts its anti-fibrosis effects in atriums.Results: After 28 days of AngⅡ stimulation, rats in SAC/VAL group exhibited reduced reduced extent of atrial fibrosis, inhibited proliferation, migration, and differentiation of atrial fibroblasts and decreased susceptibility to atrial fibrillation. We further found that SAC/VAL exerted its effect on AngⅡ-induced atrial fibrosis by inhibiting the p-Smad2/3, p-JNK, and p-p38 MAPK signaling pathways in vivo. Conclusions: Our study provided experimental evidence for the inhibition of atrial fibrosis and reduced susceptibility to AF by SAC/VAL. These results emphasize the importance of SAC/VAL in the prevention of AngⅡ-induced atrial fibrosis and may help to enrich the options for atrial fibrillation pharmacotherapy.

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Integrins: Key Targets in Tissue Fibrosis and Tumor Stroma

Veerman

Prakash

2023

Integrins in Health and Disease

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MFGE8 attenuates Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway

Cited by 37 publications

References 38 publications

MFGE8 is down‐regulated in cardiac fibrosis and attenuates endothelial‐mesenchymal transition through Smad2/3‐Snail signalling pathway

MFGE8 is down‐regulated in cardiac fibrosis and attenuates endothelial‐mesenchymal transition through Smad2/3‐Snail signalling pathway

Sacubitril/valsartan Decreased Atrial Fibrillation Susceptibility by Inhibiting Angiotensin II-induced Atrial Fibrosis through p-Smad2/3, p-JNK, and p-p38 Signaling Pathways

Integrins: Key Targets in Tissue Fibrosis and Tumor Stroma

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