Nuclear receptor subfamily 4 group A member 1 promotes myocardial ischemia/reperfusion injury through inducing mitochondrial fission factor-mediated mitochondrial fragmentation and inhibiting FUN14 domain containing 1-depedent mitophagy

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

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3D‐Printed Myocardium‐Specific Structure Enhances Maturation and Therapeutic Efficacy of Engineered Heart Tissue in Myocardial Infarction

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Abstract Despite advancements in engineered heart tissue (EHT), challenges persist achieving accurate dimensional accuracy of scaffolds and maturing human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs), a primary source functional cardiac cells. Drawing inspiration from muscle fiber arrangement, three‐dimensional (3D)‐printed multi‐layered microporous polycaprolactone (PCL) scaffold is created with interlayer angles set at 45° to replicate the precise structure native tissue. Compared control group 90° PCL scaffolds, exhibited superior biocompatibility for cell culture improved hiPSC‐CM maturation calcium handling. RNA sequencing demonstrated that promotes mature phenotype hiPSC‐CMs by upregulating ion channel genes. Using scaffold, multi‐cellular EHT successfully constructed, incorporating cardiomyocytes, endothelial cells, mesenchymal These complex EHTs significantly enhanced engraftment vivo, attenuated ventricular remodeling, function mouse myocardial infarction. In summary, myocardium‐specific structured developed this study represents promising advancement cardiovascular regenerative medicine.

Язык: Английский

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Innovative Approaches to Boost Mesenchymal Stem Cells Efficacy in Myocardial Infarction Therapy

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101476 - 101476

Опубликована: Янв. 9, 2025

Stem cell-based therapy has emerged as a promising approach for heart repair, potentially regenerating damaged tissue and improving outcomes patients with disease. However, the efficacy of stem therapies remains limited by several challenges, including poor cell survival, low retention rates, integration, functional outcomes. This article reviews current enhancement strategies to optimize mesenchymal cardiac repair. Key approaches include optimizing delivery methods, enhancing engraftment, promoting functions through genetic molecular modifications, paracrine effects cells, leveraging biomaterials engineering techniques. By focusing on these techniques, paper highlights innovative that can transform into more viable effective treatment option The ongoing research technological advancements continue push boundaries, hoping make mainstream

Язык: Английский

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Placement of an elastic, biohybrid patch in a model of right heart failure with pulmonary artery banding

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 20, 2025

Introduction In a model of right heart failure secondary to pulmonary artery banding (PAB), mechanical approach using an elastic, biodegradable epicardial patch with integrated extracellular matrix digest was evaluated for its potential inhibit disease progression. Methods Adult male syngeneic Lewis rats aged 6–7 weeks old were used. Biohybrid cardiac patches generated by co-processing poly(ester carbonate urethane) urea (PECUU) and the porcine matrix. Three after PAB, attached epicardium ventricle (RV). Cardiac function echocardiography catheterization 9 comparing (n = 7) sham 10) groups. Results Nine RV wall thickened, cavity enlarged reduced left ventricular cavity, interstitial fibrosis increased. However, these effects diminished in group. Left ejection fraction group higher than ( p < 0.001), end-systolic pressure lower 0.045), tricuspid annular plane systolic excursion improved 0.007). addition, von Willebrand factor expression significantly greater Conclusions The placement degradable, biohybrid onto fixed afterload myocardial output, moderated stress, associated fibrosis.

Язык: Английский

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A functional cardiac patch promotes cardiac repair by modulating the CCR2− cardiac-resident macrophage niche and their cell crosstalk

Cell Reports Medicine, Год журнала: 2025, Номер unknown, С. 101932 - 101932

Опубликована: Янв. 1, 2025

C-C chemokine receptor type 2 (CCR2-) cardiac-resident macrophages (CCR2- cRMs) are known to promote cardiac repair after myocardial infarction (MI). However, the substantial depletion and slow recovery of CCR2- cRMs pose significant barriers in recovery. Here, we construct a functional conductive patch (CCP) that can provide exogenously elastic microenvironment induce endogenously reparative mediated by for MI repair. This CCP exhibits suitable mechanical properties, conductivity, high water retention, reminiscent natural myocardium, which actively engage modulating cRM renewal their cell crosstalk. The expression Connexin43 between cardiomyocytes (CMs) regulate paracrine signaling activate epicardial epithelial-to-mesenchymal transition (EMT) toward endothelial cells using rat Wt1CreERT2 transgenic lineage tracing mice. Overall, this study provides promising strategy synergistic

Язык: Английский

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Roles of retinoic acid-related orphan receptor α in high glucose-induced cardiac fibroblasts proliferation

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 30, 2025

Diabetic cardiomyopathy, characterized by myocardial fibrosis, is a common complication of diabetes. Retinoic acid-related orphan receptor α (RORα) participates in various pathological and physiological cardiovascular processes. The current research aims to elucidate the roles mechanisms RORα high glucose induced cardiac fibroblasts proliferation. Primary neonatal were isolated from Sprague-Dawley rats, pre-administrated with antagonist SR3335 (20 µM) or agonist SR1078 (10 followed stimulation normal (5.5 mM) (33.3 respectively. Lactate Dehydrogenase (LDH) release into culture medium, cellular adenosine-triphosphate (ATP), cell number detected. Expressions Collagen I, III, proliferating nuclear antigen (PCNA), α-smooth muscle actin (α-SMA), receptor-interacting protein kinase 1 (RIPK1) 3 (RIPK3) evaluated. extent oxidative stress was also assessed. Our study found that elevated LDH release, reduced ATP production, increased cells numbers, expression PCNA, α-SMA, RIPK1 RIPK3, decreased mitochondrial membrane potential, strengthened intensity dihydroethidium (DHE) MitoSOX fluorescence. Above effects all further exacerbated but significantly reversed SR1078. In conclusion, promoted injury proliferation, enhanced collagen synthesis, facilitated necroptosis stimulation, whereas showed opposing effects. proposed as novel target against glucose-induced which beneficial clarify ideal therapeutic implication for diabetic cardiomyopathy.

Язык: Английский

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3D Bioprinted Cardiac Patch Devices for Regenerative Therapies

Current Treatment Options in Cardiovascular Medicine, Год журнала: 2025, Номер 27(1)

Опубликована: Янв. 31, 2025

Язык: Английский

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MT2A promotes angiogenesis in chronically ischemic brains through a copper–mitochondria regulatory mechanism

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 6, 2025

Язык: Английский

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Inflammatory Cell-Targeted Delivery Systems for Myocardial Infarction Treatment

Bioengineering, Год журнала: 2025, Номер 12(2), С. 205 - 205

Опубликована: Фев. 19, 2025

Myocardial infarction (MI) is a cardiovascular disease (CVD) with high morbidity and mortality worldwide, which serious threat to human life health. Inflammatory immune responses are initiated immediately after MI, unbalanced inflammation post-MI can lead cardiac dysfunction, scarring, ventricular remodeling, emphasizing the critical need for an effective inflammation-regulating treatment. With development of novel therapies, drug delivery system specific inflammatory cells offers significant potential. In this review, we introduce fibroblasts involved in MI summarize newly developed systems related use injectable hydrogels, patches, nanoparticles, extracellular vesicles (EVs). Finally, highlight recent trends cell-targeting involving different strategies that facilitate treatment MI.

Язык: Английский

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Polymeric Heart Valves: Do They Represent a Reliable Alternative to Current Prosthetic Devices?

Polymers, Год журнала: 2025, Номер 17(5), С. 557 - 557

Опубликована: Фев. 20, 2025

With the increasing number of people suffering from heart valve diseases (e.g., stenosis and/or insufficiency), attention paid to prosthetic valves has grown significantly. Developing a device that fully replaces functionality native remains huge challenge. Polymeric (PHVs) represent an appealing option, offering potential combine robustness mechanical with enhanced biocompatibility bioprosthetic ones. Over years, novel biomaterials (such as promising new polymers and nanocomposites) innovative designs have been explored for possible applications in manufacturing PHVs. This work provides comprehensive overview PHVs' evolution terms materials, design, fabrication techniques, including vitro vivo studies. Moreover, it addresses drawbacks associated PHV implementation, such their limited propensity sudden failure vivo. Future directions further development are presented. Notably, PHVs can be particularly relevant transcatheter application, most recent minimally invasive approach replacement. Despite current challenges, area research revolutionize treatment diseases, more durable less solutions patients.

Язык: Английский

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