Increased Expression of Connective Tissue Growth Factor and Transforming Growth Factor-Beta-1 in Atrial Myocardium of Patients with Chronic Atrial Fibrillation

Li, Yong; Zhao, Jian; Yang, Zong Ying; Chen, Lin; Wang, Xue Feng; Yan, Rui; Xiao, Ying

doi:10.1159/000347126

Cited by 42 publications

(24 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CTGF, an immediate response gene of the CCN (Cyr61, Ctgf, Nov) family, is a critical cytokine in the pathophysiology of fibrosis that upregulates COL1 and COL3 in cardiomyocytes [61]. CTGF is essential in AGTR1-mediated intracellular signaling and can activate cytokines, such as transforming growth factor-β, resulting in myocardial remodeling, vascular fibrosis, endothelial dysfunction, and atherosclerosis progress [62].…”

Section: Discussionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

View full text Add to dashboard Cite

Epidemiological studies have revealed that offspring conceived by in vitro fertilization (IVF) have an elevated risk of cardiovascular malformations at birth, and are more predisposed to cardiovascular diseases. The renin-angiotensin system (RAS) plays an essential role in both the pathogenesis of congenital heart disease in fetuses and cardiovascular dysfunction in adults. This study aimed to assess the relative expression levels of genes in the RAS pathway in mice conceived using IVF, compared to natural mating with superovulation. Results demonstrated that expression of the angiotensin II receptor type 1 (AGTR1), connective tissue growth factor (CTGF), and collagen 3 (COL3), in the myocardial tissue of IVF-conceived mice, was elevated at 3 weeks, 10 weeks, and 1.5 years of age, when compared to their non-IVF counterparts. These data were supported by microRNA microarray analysis of the myocardial tissue of aged IVF-conceived mice, where miR-100, miR-297, and miR-758, which interact with COL3, AGTR1, and COL1 respectively, were upregulated when compared to naturally mated mice of the same age. Interestingly, bisulfite sequencing data indicated that IVF-conceived mice exhibited decreased methylation of CpG sites in Col1. In support of our in vivo investigations, miR-297 overexpression was shown to upregulate AGTR1 and CTGF, Effects of in vitro fertilization on myocardium, 2018, Vol. 99, No. 6 1277 and increased cell proliferation in cultured H9c2 cardiomyocytes. These findings indicate that the altered expression of RAS in myocardial tissue might contribute to cardiovascular malformation and/or dysfunction in IVF-conceived offspring. Furthermore, these cardiovascular abnormalities might be the result of altered DNA methylation and abnormal regulation of microRNAs. Summary SentenceAltered expression of the renin-angiotensin system in myocardial tissue might contribute to an increased risk of cardiovascular malformations and dysfunction in IVF offspring, and is involved in abnormal regulations of DNA methylation and microRNAs.

show abstract

Section: Discussionmentioning

confidence: 99%

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Wang

Zhang

Fang

et al. 2018

Biology of Reproduction

View full text Add to dashboard Cite

show abstract

“…106 CCN2 expression is elevated in cardiac hypertrophy and failing hearts 77,102 and in patients with permanent and non-paroxysmal AF. 90,92 Elevated CCN2 levels were predictive of AF recurrence after catheter ablation of non-paroxysmal AF, independent of other risk factors. 92 In experimental models using isolated cardiomyocytes, CCN2 increased cell size through AKT signaling 101,107 and induced fibrosis with upregulation of collagen I and III in a pacing-induced HF model through TGF-β1-independent, but angiotensin II-dependent manner.…”

Section: Mechanism Underlying Atrial Fibrillation and Circulatory Biomentioning

confidence: 93%

“…77,102,103 The expression of CCN2 is induced by angiotensin II 91,101,103 7 and TGF-β1 in cardiac fibroblasts and cardiomyocytes. 104 CCN2 acts as a mediator of TGF-β1 effect 102 through the Smad pathway 90 and angiotensin II effect through small G-protein Rac-1and nicotinamide adenine dinucleotide phosphate oxidase. 91 TGF-β1 appears to be involved in the initial acute phase of inflammation and repair after myocardial necrosis, whereas CCN2 is found in the ongoing fibrosis after myocardial injury 105 and has been suggested to facilitate fibrosis promoted by hemodynamic stress.…”

Section: Mechanism Underlying Atrial Fibrillation and Circulatory Biomentioning

confidence: 99%

Circulating Biomarkers Predictive of Postoperative Atrial Fibrillation

Turagam

Mirza

Werner

et al. 2016

Cardiology in Review

View full text Add to dashboard Cite

Postoperative atrial fibrillation (PoAF), a common complication of cardiac surgery, contributes significantly to morbidity, mortality, and increasing health care costs. Despite advances in surgical and medical management, the overall incidence of PoAF has not changed significantly, partly due to the limited understanding of mechanisms underlying acute surgery-related factors, such as myocardial injury, inflammation, sympathetic activation, and oxidative stress, which play an important role in the initiation of PoAF, while a preexisting atrial substrate appears to be more important in the maintenance of this dysrhythmia. Thus, in a majority of patients, PoAF becomes a manifestation of an underlying arrhythmogenic substrate that is unmasked following acute surgical stress. As such, the ability to identify which patients have this proarrhythmic substrate and are, therefore, at high risk for developing AF postoperatively, is important for the improved selection for prophylactic interventions, closer monitoring for complications, and establishing the probability of AF in the long term. This review highlights the role of the underlying substrate in promoting PoAF, proposed mechanisms, and the potential role of serum biomarkers to identify patients at risk for PoAF.

show abstract

“…TGF-β1 is another profibrotic molecule upregulated in AF, as demonstrated in animal models of AF (30,129) as well as in clinical studies on patients with AF (139,193). TGF-β1 is an established positive regulator of cardiac fibrosis and its specific overexpression in the heart leads to atrial fibrosis and increased susceptibility to AF (54, 58), suggesting that TGF-β1 is sufficient for developing an AF-prone substrate (193).…”

Section: Mechanisms Underlying Atrial Fibrillationmentioning

confidence: 93%

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

Pellman

Sheikh

2015

Comprehensive Physiology

108

View full text Add to dashboard Cite

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation.

show abstract

Increased Expression of Connective Tissue Growth Factor and Transforming Growth Factor-Beta-1 in Atrial Myocardium of Patients with Chronic Atrial Fibrillation

Cited by 42 publications

References 76 publications

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Alteration in the expression of the renin-angiotensin system in the myocardium of mice conceived by in vitro fertilization†

Circulating Biomarkers Predictive of Postoperative Atrial Fibrillation

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

Contact Info

Product

Resources

About