Role of TGF-&amp;beta; on cardiac structural and electrical remodeling

Ramos-Mondragón, Roberto; Galindo, Carlos A; Ávila, Guillermo

doi:10.2147/vhrm.s3985

Cited by 42 publications

(7 citation statements)

References 93 publications

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“…One of its gene targets is the mothers against decapentaplegic homolog 4 ( SMAD4 ) which upon binding with DACH1 can result in repression of TGFβ signaling and TGFβ-induced apoptosis [23] . In this regard, increased TGFβ1 activity has been implicated in heart and vascular development, hypertension and progressive myocardial fibrosis [24] , [25] . In a recent proof-of-concept analysis, researchers merged co-expression and interaction networks and detected/inferred novel networks to explain the frequent but not invariable coexistence of diabetes and other dysfunctions.…”

Section: Discussionmentioning

confidence: 99%

Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

et al. 2014

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In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57–3.96, P = 8.4×10−5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02–1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07–2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19–9.19, P = 0.0214) and 3.27(1.25–11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese.

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Section: Discussionmentioning

confidence: 99%

Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

et al. 2014

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“…Myocardial fibrogenesis is induced by TGF-b1 (13,15,(24)(25)(26). To test whether TGF-b1 is increased in deceased COVID-19 patients, we measured TGF-b1 mRNA levels by quantitative RT-PCR in left ventricular tissue taken from patients with COVID-19.…”

Section: Fibrotic Markers Are Increased In Deceased Covid-19 Patientsmentioning

confidence: 99%

“…TGF-b1 binding to its receptor leads to phosphorylation of intracellular SMAD3, which upregulates profibrotic genes (15,24,25), resulting in increased expression of collagens or fibronectin. Although altered levels of SMAD3 RNA would not necessarily equate to altered SMAD3 activity, it has been shown in a variety of tissues that TGF-b1-induced upregulation of SMAD3 can be an important inducer of reactive oxygen species (ROS) via upregulation of NADPH oxidases II and IV (NOX2/NOX4) (25)(26)(27)(28)(29).…”

Section: Fibrotic Markers Are Increased In Deceased Covid-19 Patientsmentioning

confidence: 99%

Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

et al. 2021

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Increased left ventricular fibrosis has been reported in patients hospitalized with coronavirus disease 2019 (COVID-19). It is unclear whether this fibrosis is a consequence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection or a risk factor for severe disease progression. We observed increased fibrosis in the left ventricular myocardium of deceased COVID-19 patients, compared with matched controls. We also detected increased mRNA levels of soluble interleukin-1 receptor-like 1 (sIL1-RL1) and transforming growth factor β1 (TGF-β1) in the left ventricular myocardium of deceased COVID-19 patients. Biochemical analysis of blood sampled from patients admitted to the emergency department (ED) with COVID-19 revealed highly elevated levels of TGF-β1 mRNA in these patients compared to controls. Left ventricular strain measured by echocardiography as a marker of pre-existing cardiac fibrosis correlated strongly with blood TGF-β1 mRNA levels and predicted disease severity in COVID-19 patients. In the left ventricular myocardium and lungs of COVID-19 patients, we found increased neuropilin-1 (NRP-1) RNA levels, which correlated strongly with the prevalence of pulmonary SARS-CoV-2 nucleocapsid. Cardiac and pulmonary fibrosis may therefore predispose these patients to increased cellular viral entry in the lung, which may explain the worse clinical outcome observed in our cohort. Our study demonstrates that patients at risk of clinical deterioration can be identified early by echocardiographic strain analysis and quantification of blood TGF-β1 mRNA performed at the time of first medical contact.

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“…Inflammation and oxidative stress have been found to be responsible of many molecular mechanisms of CD including activation of immune cells such as macrophages, T and B cells, neutrophils and inflammatory cytokines (IL-6, TNF-α). These cytokines and activated immune cells could affect the contractility and electrical myocytes stability inducing fibroblast activation and cellular fibrosis [24][25][26]. These atrial changes provide reentrant arrhythmias confirmed clinically and electrocardiogram [27].…”

Section: Discussionmentioning

confidence: 83%

Celiac Disease and Risk of Atrial Fibrillation: A Meta-analysis and Systematic Review

Hidalgo

Boonpheng

Nasr

et al. 2020

Cureus

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IntroductionSeveral studies have found celiac disease may be associated with a variety of cardiac manifestations. Atrial fibrillation (AF) is one of the most common arrhythmias that can cause significant morbidity. However, the risk of atrial fibrillation in patients with celiac disease according to epidemiological studies remains unclear. The aim of this meta-analysis study is to assess the risk of atrial fibrillation in patients diagnosed with celiac disease compared to controls. MethodsA systematic literature review was conducted in MEDLINE, EMBASE, Cochrane databases from inception through December 2017 to identify studies that evaluated the risk of atrial fibrillation in patients with celiac disease. We included randomized controlled trial, cross sectional and cohort studies that reported the odds ratio, relative risk, hazard ratio, and standardized incidence ratio comparing the risk of developing atrial fibrillation among patients with celiac disease, versus patients without celiac disease as control. The Newcastle-Ottawa scale was used to determine the quality of the studies. Effect estimates from individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. ResultsCeliac disease is an autoimmune condition. This inflammatory state predisposes patients to develop AF. After a review of the literature, four observational studies with a total of 64,397 participants were enrolled. The association between celiac disease and increased risk of atrial fibrillation was significant, with a pooled OR of 1.38 (95% CI: 1.01-1.88). No publication bias as assessed by the funnel plots and Egger's regression asymmetry test with p = 0.54. However, the heterogeneity of the included studies was high (I2 = 96). ConclusionA significant association between celiac disease and risk of atrial fibrillation was reported in this study. There is a 38% increased risk of atrial fibrillation. Additional studies are needed to clarify the mechanistic link between atrial fibrillation and celiac disease. Some of the limitations of this study are that all were observational studies, some were medical registry-based and there was high heterogeneity between studies.

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Role of TGF-β on cardiac structural and electrical remodeling

Cited by 42 publications

References 93 publications

Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

Cardiac Fibrosis Is a Risk Factor for Severe COVID-19

Celiac Disease and Risk of Atrial Fibrillation: A Meta-analysis and Systematic Review

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