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Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE218761 | GEO | 2024/12/14

REPOSITORIES: GEO

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Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [Visium]

Project description:Fibrosis is important pathogenesis in heart failure with preserved ejection fraction (HFpEF). We previously reported that the overexpression of cardiac transcription factors, Mef2c/Gata4/Tbx5/Hand2 (MGTH) could directly reprogram cardiac fibroblasts (CFs) into induced CMs (iCMs) and reduce fibrosis. Here we show that in vivo cardiac reprogramming generated iCMs from resident CFs, improved cardiac function, and reversed fibrosis in HFpEF model using a novel transgenic mouse system. Visium revealed spatial information on changes in gene expression in HFpEF.

2024-12-14 | GSE218759 | GEO

Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [scRNA-seq]

Project description:Fibrosis is important pathogenesis in heart failure with preserved ejection fraction (HFpEF). We previously reported that the overexpression of cardiac transcription factors, Mef2c/Gata4/Tbx5/Hand2 (MGTH) could directly reprogram cardiac fibroblasts (CFs) into induced CMs (iCMs) and reduce fibrosis. Here we show that in vivo cardiac reprogramming generated iCMs from resident CFs, improved cardiac function, and reversed fibrosis in HFpEF model using a novel transgenic mouse system. scRNA-seq of non-cardiomyocytes revealed that cardiac reprogramming suppressed fibroblastic gene expression via conversion of profibrotic profile to a quiescent state. Thus, in vivo cardiac reprogramming may be a promising approach for HFpEF.

2024-12-14 | GSE218757 | GEO

Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [RNA-seq]

Project description:Fibrosis is important pathogenesis in heart failure with preserved ejection fraction (HFpEF). We previously reported that the overexpression of cardiac transcription factors, Mef2c/Gata4/Tbx5/Hand2 (MGTH) could directly reprogram cardiac fibroblasts (CFs) into induced CMs (iCMs) and reduce fibrosis. Here we show that in vivo cardiac reprogramming generated iCMs from resident CFs, improved cardiac function, and reversed fibrosis in HFpEF model using a novel transgenic mouse system. RNA-seq revealed that the MGTH activated the cardiac program and concomitantly suppressed fibroblast and inflammatory signatures. Thus, cardiac reprogramming improves HFpEF via myocardial regeneration and anti-fibrosis.

2024-12-14 | GSE218733 | GEO

Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction

Project description:Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction

| PRJNA905408 | ENA

Primary and Secondary Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

Project description:Approximately 50% of patients with symptoms and signs of heart failure have a left ventricular ejection fraction (LVEF) ≥50% and are often simply referred to as 'heart failure with preserved EF', 'HFpEF'. Many of such patients have HF secondary to specific cardiac conditions (i.e., valvular or pericardial disease) in which the symptoms and signs occur despite the LVEF being preserved due to diastolic dysfunction secondary to the underlying disease (secondary HFpEF), differently from those HFpEF patients in which the impaired LV filling is due to a primary diastolic dysfunction (primary HFpEF). When primary HFpEF patients are properly diagnosed, they appear to have a milder form of HF with a lower cardiovascular mortality compared with HFrEF and secondary HFpEF population, but a risk of HF hospitalization that is significantly higher than patients with similar cardiovascular risk factors but without the diagnosis of HFpEF. We herein review the diagnostic approach to HFpEF and present a differential diagnosis of HFpEF in a primary and secondary form.

| S-EPMC6608585 | biostudies-literature

Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [Visium]

Project description:Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [Visium]

| PRJNA905414 | ENA

Diastolic dysfunction in individuals with and without heart failure with preserved ejection fraction.

Project description:AimLeft ventricular diastolic dysfunction (DD), a common finding in the general population, is considered to be associated with heart failure with preserved ejection faction (HFpEF). Here we evaluate the prevalence and correlates of DD in subjects with and without HFpEF in a middle-aged sample of the general population.Methods and resultsFrom the first 10,000 participants of the population-based Hamburg City Health Study (HCHS), 5913 subjects (mean age 64.4 ± 8.3 years, 51.3% females), qualified for the current analysis. Diastolic dysfunction (DD) was identified in 753 (12.7%) participants. Of those, 11.2% showed DD without HFpEF (ALVDD) while 1.3% suffered from DD with HFpEF (DDwHFpEF). In multivariable regression analysis adjusted for major cardiovascular risk factors, ALVDD was associated with arterial hypertension (OR 2.0, p < 0.001) and HbA1c (OR 1.2, p = 0.007). Associations of both ALVDD and DDwHFpEF were: age (OR 1.7, p < 0.001; OR 2.7, p < 0.001), BMI (OR 1.2, p < 0.001; OR 1.6, p = 0.001), and left ventricular mass index (LVMI). In contrast, female sex (OR 2.5, p = 0.006), atrial fibrillation (OR 2.6, p = 0.024), CAD (OR 7.2, p < 0.001) COPD (OR 3.9, p < 0.001), and QRS duration (OR 1.4, p = 0.005) were strongly associated with DDwHFpEF but not with ALVDD.ConclusionThe prevalence of DD in a sample from the first 10,000 participants of the population-based HCHS was 12.7% of whom 1.3% suffered from HFpEF. DD with and without HFpEF showed significant associations with different major cardiovascular risk factors and comorbidities warranting further research for their possible role in the formation of both ALVDD and DDwHFpEF.

| S-EPMC8971165 | biostudies-literature

Myocardial strain for heart failure with preserved ejection fraction but without diastolic dysfunction.

Project description:AimsSome patients with apparent heart failure (HF) have an ejection fraction (EF) ≥ 50% and elevated levels of natriuretic peptides (NPs), but no significant diastolic dysfunction. Among these, some may have HF, others may not. Myocardial strain is an excellent prognostic factor.Methods and resultsAmong 4312 consecutive patients with acute HF from three tertiary hospitals, we included 355 patients with EF of ≥50% and elevated levels of NPs, without significant diastolic dysfunction. Patients were classified as having impaired global longitudinal strain (GLS < 16%) or normal GLS (GLS ≥ 16%). The primary endpoint was 5 year all-cause mortality. The mean age was 70.3 years and 49% were female. Overall, 107 patients (30.1%) died at 5 years. As per the definition, 176 (49.6%) patients had impaired GLS and 179 (50.4%) had normal GLS. Patients with normal GLS had lower 5 year all-cause mortality than those with impaired GLS (P < 0.001). When comparing with the 11 365 age-matched and sex-matched controls, patients with normal GLS had the same long-term survival as the controls (P = 0.834), whereas those with impaired GLS had 48% increased risk of all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.17-1.89).ConclusionsAmong patients with apparent HF and preserved EF but without diastolic dysfunction, those with impaired GLS may be considered to have HF.

| S-EPMC9715819 | biostudies-literature

Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [scRNA-seq]

Project description:Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [scRNA-seq]

| PRJNA905412 | ENA

Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [RNA-seq]

Project description:Cardiac reprogramming and Gata4 overexpression reduce fibrosis and improve diastolic dysfunction in heart failure with preserved ejection fraction [RNA-seq]

| PRJNA905370 | ENA

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