Life Sciences, Год журнала: 2024, Номер 361, С. 123294 - 123294
Опубликована: Дек. 5, 2024
Язык: Английский
International Journal of Biological Sciences, Год журнала: 2024, Номер 20(11), С. 4458 - 4475
Опубликована: Янв. 1, 2024
This study investigated the mechanism by which NR4A1 regulates mitochondrial fission factor (Mff)-related and FUN14 domain 1 (FUNDC1)-mediated mitophagy following cardiac ischemia-reperfusion injury(I/R). Our findings showed that damage regulation was positively correlated with pathological pan-apoptosis of myocardial cell mitochondria. Compared wild-type mice (WT), NR4A1-knockout exhibited resistance to injury fission, characterized activation. Results increased expression level, activating mediated Mff restoring phenotype FUNDC1. The inactivation FUNDC1 phosphorylation could not mediate normalization in a timely manner, leading an excessive stress response unfolded proteins imbalance homeostasis. process disrupted quality control network, accumulation damaged mitochondria activation pan-apoptotic programs. data indicate is novel critical target I/R exertsand negative regulatory effects Mff-mediated mito-fission inhibiting FUNDC1-mediated mitophagy. Targeting crosstalk balance between NR4A1-Mff-FUNDC1 potential approach for treating I/R.
Язык: Английский
Процитировано
17
Redox Biology, Год журнала: 2024, Номер 76, С. 103321 - 103321
Опубликована: Авг. 19, 2024
Cell death constitutes a critical component of the pathophysiology cardiovascular diseases. A growing array non-apoptotic forms regulated cell (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified is intimately linked to various conditions. These RCD are governed by genetically programmed mechanisms within cell, with epigenetic modifications being common crucial regulatory method. Such include DNA methylation, RNA histone acetylation, non-coding RNAs. This review recaps roles modifications, RNAs in diseases, well which regulate key proteins involved death. Furthermore, we systematically catalog existing pharmacological agents targeting novel their action article aims underscore pivotal role precisely regulating specific pathways thus offering potential new therapeutic avenues that may prove more effective safer than traditional treatments.
Язык: Английский
Процитировано
7
Circulation Research, Год журнала: 2024, Номер 135(12), С. 1161 - 1174
Опубликована: Окт. 28, 2024
BACKGROUND: Given the growing acknowledgment of detrimental effects excessive myocardial fibrosis on pathological remodeling after ischemia-reperfusion injury (I/R), targeting modulation may offer protective and therapeutic advantages. However, effective clinical interventions therapies that target remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear. METHODS: The expression FAP (fibroblast activation protein) was studied in mouse hearts I/R. CAR-Ms were generated FAP-expressing cardiac fibroblasts phagocytosis activity tested vitro. efficacy safety treating evaluated vivo. RESULTS: significantly upregulated activated as early 3 days Upon demonstrating their ability engulf FAP-overexpressing fibroblasts, we intravenously administered mice at found improved function reduced No toxicities associated with detected heart or other organs 2 weeks Finally, conferred long-term cardioprotection against CONCLUSIONS: Our proof-of-concept study demonstrates potential alleviating potentially opens new avenues for treatment range diseases include fibrotic phenotype.
Язык: Английский
Процитировано
6
Journal of Bioenergetics and Biomembranes, Год журнала: 2025, Номер unknown
Опубликована: Фев. 21, 2025
Язык: Английский
Процитировано
0
Experimental and Molecular Pathology, Год журнала: 2025, Номер 141, С. 104957 - 104957
Опубликована: Фев. 27, 2025
Язык: Английский
Процитировано
0
Analytical Biochemistry, Год журнала: 2025, Номер unknown, С. 115840 - 115840
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0
Cardiovascular Toxicology, Год журнала: 2024, Номер 24(9), С. 918 - 928
Опубликована: Июль 18, 2024
Язык: Английский
Процитировано
3
International Journal of Medical Sciences, Год журнала: 2024, Номер 21(13), С. 2464 - 2479
Опубликована: Янв. 1, 2024
MAPKK4 has been implicated in the pathological mechanisms underlying myocardial and vascular injury, specifically influencing endothelial cell damage programmed death via subcellular pathways. Nevertheless, regulatory role of coronary microvascular injury following infarction remains unconfirmed, exploration targeted mitochondrial protective therapeutic agents unaddressed. In light this gap, we established a gene-modified mouse model ischemia-reperfusion employed Buyang Huanwu decoction (BYHW), traditional cardiovascular formula, to assess its efficacy treating post-ischemia-reperfusion. The study aimed elucidate mechanism by which BYHW mitigates induced through attenuation apoptosis. Experimental outcomes revealed that high-dose significantly ameliorated post-ischemia-reperfusion, restoring structural integrity microvasculature reducing inflammation oxidative stress. Contrarily, transgenic mice overexpressing MAPKK4, intervention failed attenuate To further investigate, simulated hypoxia/reoxygenation cells using MAPKK4-related cellular gene modification model. results indicated attenuates inflammatory enhances viability hypoxic stress, inhibiting apoptosis pathway. However, overexpression MAPKK4/p38 negated effects BYHW, showing no impact on stress under conditions. Molecular interaction studies confirmed active components Astragaloside IV Ligustrazine, interact with MAPKK4/P38 axis.
Язык: Английский
Процитировано
1
Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)
Опубликована: Окт. 29, 2024
Abstract Cardiovascular disease (CVD) remains a global economic burden even in the 21st century with 85% of deaths resulting from heart attacks. Despite efforts reducing risk factors, and enhancing pharmacotherapeutic strategies, challenges persist early identification progression functional recovery damaged hearts. Targeting mitochondrial dysfunction, key player pathogenesis CVD has been less successful due to its role other coexisting diseases. Additionally, it is only organelle an agathokakological function that remedy poison for cell. In this review, we describe origins cardiac mitochondria heteroplasmy subpopulations namely interfibrillar, subsarcolemmal, perinuclear, intranuclear maintaining disease-associated remodeling. The cumulative evidence retrograde communication nucleus addressed, highlighting need study genotype-phenotype relationships specific functions by using approaches like genome-wide association (GWAS). Finally, discuss practicality computational methods combined single-cell sequencing technologies address genetic screening contributory genes towards CVD.
Язык: Английский
Процитировано
0
Small Science, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 21, 2024
Fibrosis is a pathological process characterized by the excessive deposition of extracellular matrix in tissue's space, leading to structural injury and organ dysfunction, even failure, posing threat human life. Despite mounting evidence suggesting that fibrosis reversible, effective treatments for fibrotic diseases are lacking. Accumulating has elucidated ribonucleic acid (RNA) modifications have emerged as novel mechanisms regulating gene expression. N6‐methyladenosine (m6A) modification well‐known prevalent RNA posttranscriptional participates essential biological processes such splicing, translation, degradation. It tightly implicated wide range cellular various diseases, particularly fibrosis. The m6A dynamic reversible regulated methylases, commonly known “writers,” demethylases referred “erasers,” while recognized “readers.” suggests on RNAs associated with visceral organs including lungs, heart, liver, kidney. In this review, recent advances impact methylation highlighted potential prospects therapy treating discussed.
Язык: Английский
Процитировано
0