TGF-β1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease

Sun, Yu; Huang, Ziyang; Wang, Zhenhua; Li, Cuiping; Meng, Xianliang; Zhang, Yunjiao; Ma, Nan

doi:10.1007/s11010-015-2431-1

Cited by 22 publications

(11 citation statements)

References 28 publications

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“… 24 Changes in the ECM of atrial fibroblast in rheumatic heart disease have been associated with TIMP-4 expression. 25 …”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinases in exercise and obesity

Jaoude¹,

Koh²

2016

VHRM

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Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endoproteinases that have the ability to break down extracellular matrix. The large range of MMPs’ functions widens their spectrum of potential role as activators or inhibitors in tissue remodeling, cardiovascular diseases, and obesity. In particular, MMP-1, -2, and -9 may be associated with exercise and obesity. Thus, the current study reviewed the effects of different types of exercise (resistance and aerobic) on MMP-1, -2, and -9. Previous studies report that the response of MMP-2 and -9 to resistance exercise is dependent upon the length of exercise training, since long-term resistance exercise training increased both MMP-2 and -9, whereas acute bout of resistance exercise decreased these MMPs. Aerobic exercise produces an inconsistent result on MMPs, although some studies showed a decrease in MMP-1. Obesity is related to a relatively lower level of MMP-9, indicating that an exercise-induced increase in MMP-9 may positively influence obesity. A comprehensive understanding of the relationship between exercise, obesity, and MMPs does not exist yet. Future studies examining the acute and chronic responses of these MMPs using different subject models may provide a better understanding of the molecular mechanisms that are associated with exercise, obesity, and cardiovascular disease.

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“… 24 Changes in the ECM of atrial fibroblast in rheumatic heart disease have been associated with TIMP-4 expression. 25 …”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinases in exercise and obesity

Jaoude¹,

Koh²

2016

VHRM

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“…TGF-β signaling is involved in the differentiation of fibroblasts into myofibroblasts[ 62 ] and is a key regulator of myofibroblast biology. [ 61 ] Recent studies have also revealed cooperative interactions between YAP and TGF-β-regulated Smads that couple mechanotransduction in fibroblasts to TGF-β-induced profibrotic gene expression programs that are important in fibrosis.…”

Section: Ross T Alk Between Hmentioning

confidence: 99%

Advanced Role of Hippo Signaling in Endometrial Fibrosis

Zhu

Pan

et al. 2017

Chinese Medical Journal

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Objective:Intrauterine adhesion (IUA) is a major health problem that causes infertility, menstrual irregularities, and recurrent pregnancy losses in women. Unfortunately, treatments for IUA are limited, and there are currently no effective strategies for preventing IUA recurrence. In this review, we introduced the role of Hippo signaling in the normal endometrium and IUA and described the mechanisms by which the Hippo pathway integrates with the Wnt and transforming growth factor-β (TGF-β) signaling pathways to form an intricate network governing the development of fibrosis.Data Sources:Original research articles in English that were published until July 2017 were collected from the PubMed database.Study Selection:Literature search was conducted using the search terms “endometrial fibrosis OR fibrosis AND or OR intrauterine adhesion OR Asherman syndrome OR IUA,” “Hippo AND or OR Hippo/TAZ,” “TGF-β,” and “Wnt.” Related original research articles were included in the comprehensive analysis.Results:Endometrial fibrosis is recognized as a key pathological event in the development of IUA, which is characterized by epithelial/fibroblast–myofibroblast transition. Myofibroblasts play crucial roles in the pathogenesis of fibrous scarring, and myofibroblast differentiation can be triggered by multiple signaling pathways. Hippo signaling is a critical regulator of the epithelial/fibroblast–myofibroblast transition and α-smooth muscle actin, which exhibits a specific spatiotemporal expression in the endometrium.Conclusions:Hippo signaling plays a critical role in fibrous diseases and participates in cross talks with Wnt and TGF-β signaling. Our findings not only contributed to knowledge on the pathogenesis of endometrial fibrosis, but can also serve as a useful resource for developing specific molecular inhibitors for IUA treatment and prevention.

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“…Increased afterload is associated with AF and myocardial fibrosis [ 5 ] and while TIMP-1 has been reported to increase, MMP1 was shown to decrease in AF patients’ serum [ 9 ]. Conversely, atrium TIMP-4 in AF patients with rheumatic heart disease was lower when compared with Sinus Rhythm (SR) patients, while MMP-2, type I, and type II collagen were increased in the AF group [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Atrial matrix remodeling in atrial fibrillation patients with aortic stenosis

Fragão-Marques

Miranda

Martins

et al. 2020

BMC Cardiovasc Disord

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Background This study aimed to evaluate atrium extracellular matrix remodeling in atrial fibrillation (AF) patients with severe aortic stenosis, through histological fibrosis quantification and extracellular matrix gene expression analysis, as well as serum quantification of selected protein targets. Methods A posthoc analysis of a prospective study was performed in a cohort of aortic stenosis patients. Between 2014 and 2019, 56 patients with severe aortic stenosis submitted to aortic valve replacement surgery in a tertiary hospital were selected. Results Fibrosis was significantly increased in the AF group when compared to sinus rhythm (SR) patients (p = 0.024). Moreover, cardiomyocyte area was significantly higher in AF patients versus SR patients (p = 0.008). Conversely, collagen III gene expression was increased in AF patients (p = 0.038). TIMP1 was less expressed in the atria of AF patients. MMP16/TIMP4 ratio was significantly decreased in AF patients (p = 0.006). TIMP1 (p = 0.004) and TIMP2 (p = 0.012) were significantly increased in the serum of AF patients. Aortic valve maximum (p = 0.0159) and mean (p = 0.031) gradients demonstrated a negative association with serum TIMP1. Conclusions Atrial fibrillation patients with severe aortic stenosis present increased atrial fibrosis and collagen type III synthesis, with extracellular matrix remodelling demonstrated by a decrease in the MMP16/TIMP4 ratio, along with an increased serum TIMP1 and TIMP2 proteins.

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TGF-β1 and TIMP-4 regulate atrial fibrosis in atrial fibrillation secondary to rheumatic heart disease

Cited by 22 publications

References 28 publications

Matrix metalloproteinases in exercise and obesity

Matrix metalloproteinases in exercise and obesity

Advanced Role of Hippo Signaling in Endometrial Fibrosis

Atrial matrix remodeling in atrial fibrillation patients with aortic stenosis

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