Oxidative stress and cardiomyocyte apoptosis are hallmarks of heart failure (HF) development. Plant homeodomain finger protein 8 (PHF8) is a histone demethylase downregulated in failing human hearts. Nevertheless, the potential role of PHF8 in HF remains unclear. Therefore, this study aimed to explore the biological action and molecular mechanism of PHF8 in HF.A rat model of left anterior descending coronary artery (LAD) ligation-induced HF and a cardiomyocyte model of oxygen-glucose deprivation/reperfusion (OGD/R) were developed after gain- or loss-of-function experiments in rats and cardiomyocytes, respectively. Heart function indexes, such as left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, and left ventricular fractional shortening, were detected. Changes in myocardial tissues were examined by pathological staining. Cardiomyocyte apoptosis and oxidative stress markers, such as malondialdehyde, reactive oxygen species, superoxide dismutase, and catalase, were examined. The relationship between PHF8 and forkhead box A2 (FOXA2) was analyzed by luciferase and chromatin immunoprecipitation-quantitative polymerase chain reaction assays.PHF8 was downregulated in LAD-ligated rats and OGD/R-exposed cardiomyocytes. Following PHF8 upregulation, pathological changes in myocardial tissues and heart dysfunction were improved in LAD-ligated rats. Importantly, cardiomyocyte apoptosis and oxidative stress were diminished in vivo and in vitro upon PHF8 upregulation. Mechanistically, PHF8 increased FOXA2 expression in a histone demethylase-dependent manner. FOXA2 silencing abrogated the protective effect of PHF8 upregulation on cardiomyocytes against OGD/R-induced apoptosis and oxidative stress.PHF8 exerts protective functions against cardiomyocyte apoptosis, oxidative stress, and heart dysfunction in HF, in correlation with FOXA2 upregulation. These results suggest that the PHF8/FOXA2 axis may be a promising therapeutic target to prevent HF.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1536/ihj.24-268 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.
FASEB J
March 2025
Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Neuron-derived clone 77 (Nur77), a member of the orphan nuclear receptor family, is expressed and activated rapidly in response to diverse physiological and pathological stimuli. It exerts complex biological functions, including roles in the nervous system, genome integrity, cell differentiation, homeostasis, oxidative stress, autophagy, aging, and infection. Recent studies suggest that Nur77 agonists alleviate symptoms of neurodegenerative diseases, highlighting its potential as a therapeutic target in such conditions.
View Article and Find Full Text PDFSpermidine alleviates copper-induced oxidative stress, inflammation and cuproptosis in the liver.
FASEB J
March 2025
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, P. R. China.
Copper exposure poses potential detrimental effects on both public and ecosystem health. Spermidine, an antioxidant, has shown promise in reducing oxidative stress and inflammation within the liver. However, its specific role in mitigating copper-induced hepatic cuproptosis and disturbances in copper metabolism remains unexplored.
View Article and Find Full Text PDFEffects of Complex I Inhibition on the Architecture of Neural Rosettes Differentiated from Human-Induced Pluripotent Stem Cells.
Stem Cells Dev
March 2025
Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Orchestrated changes in cell arrangements and cell-to-cell contacts are susceptible to cellular stressors during central nervous system development. Effects of mitochondrial complex I inhibition on cell-to-cell contacts have been studied in vascular and intestinal structures; however, its effects on developing neuronal cells are largely unknown. We investigated the effects of the classical mitochondrial stressor and complex I inhibitor, rotenone, on the architecture of neural rosettes-radially organized neuronal progenitor cells (NPCs)-differentiated from human-induced pluripotent stem cells.
View Article and Find Full Text PDFDual Functional Electroconductive Biofortified Electrospun Scaffold Functionalized With MWCNTs and Bacopa Monnieri for Accelerated Peripheral Nerve Regeneration.
Small
March 2025
Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, 247667, India.
Peripheral nerve injuries (PNIs) often lead to semi or complete loss of motor, sensory and autonomic functions. Although autografts are still the best option for PNI repair, their use is restricted due to the morbidity and availability of donor nerves. Because electrospun scaffolds may replicate the structure of native extracellular matrix (ECM), they provide a viable alternative.
View Article and Find Full Text PDFRole of Immune Cells in Perivascular Adipose Tissue in Vascular Injury in Hypertension.
Arterioscler Thromb Vasc Biol
March 2025
Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, Quebec, Canada (O.B., P.P., E.L.S.).
Hypertension is associated with vascular injury characterized by vascular dysfunction, remodeling, and stiffening, which contributes to end-organ damage leading to cardiovascular events and potentially death. Innate (macrophages and dendritic cells), innate-like (γδ T cells) and adaptive immune cells (T and B cells) play a role in hypertension and vascular injury. Perivascular adipose tissue that is the fourth layer of the blood vessel wall is an important homeostatic regulator of vascular tone.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!