The LINC complex in blood vessels: from physiology to pathological implications in arterioles

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract The LINC (linker of nucleoskeleton and cytoskeleton) complex is a critical component the cellular architecture that bridges cytoskeleton mediates mechanotransduction to from nucleus. Though it plays important roles in all blood vessels, arterioles this pivotal role maintaining endothelial cell integrity, regulating vascular tone, forming new microvessels modulating responses mechanical biochemical stimuli. It also smooth muscle cells fibroblasts, where possibly contractile secretory phenotypic transformation during atherosclerosis ageing, fibroblasts' migration inflammatory adventitia. Physiologically, contributes stability arteriolar structure, adaptations changes flow injury repair mechanisms. Pathologically, dysregulation or mutations components can lead compromised function, remodelling exacerbation cardiovascular diseases such as (arteriolosclerosis). This review summarizes our current understanding arterioles, highlighting its most physiological functions, exploring implications for pathology emphasizing some functional characteristics cells. By elucidating complex's health disease, we aim provide insights could improve future therapeutic strategies targeting complex‐related disorders. image

Язык: Английский

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Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation

Nutrients, Год журнала: 2024, Номер 16(5), С. 678 - 678

Опубликована: Фев. 28, 2024

Pregnancy is an extremely stressful period in a pregnant woman’s life. Currently, women’s awareness of the proper course pregnancy and its possible complications constantly growing. Therefore, significant percentage women increasingly reach for various dietary supplements during gestation. Some most popular substances included multi-ingredient are folic acid choline. Those associated with positive effects on fetal intrauterine development fewer pregnancy-associated complications. Recently, more attention has been paid to impacts specific environmental factors, such as diet, stress, physical activity, etc., epigenetic modifications, understood changes occurring gene expression without direct alteration DNA sequences. Substances choline may participate modifications by acting via one-carbon cycle, leading methyl-group donor formation. nutrients indirectly impact genome phenotype influencing process methylation. This review article presents current state knowledge use supplementation pregnancy, taking into account their maternal–fetal unit outcomes, determining mechanisms action, particular emphasis modifications.

Язык: Английский

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Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(24), С. 17522 - 17522

Опубликована: Дек. 15, 2023

Massive trauma remains a leading cause of death and global public health burden. Post-traumatic coagulopathy may be present even before the onset resuscitation, correlates with severity trauma. Several mechanisms have been proposed to explain development abnormal coagulation processes, but heterogeneity in injuries patient profiles makes it difficult define dominant mechanism. Regardless pattern death, significant role pathophysiology pathogenesis attributed exposure endothelial cells physical forces mechanical stimuli their local environment. In these conditions, cellular responses are translated into biochemical signals that induce/aggravate oxidative stress, inflammation, coagulopathy. Microvascular shear stress-induced alterations could treated or prevented by use innovative pharmacologic strategies effectively target shear-mediated dysfunction, including shear-responsive drug delivery systems novel antioxidants, targeting venous side circulation exploit beneficial antithrombogenic profile cells.

Язык: Английский

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Insights into the Molecular Mechanisms Regulating Cell Behavior in Response to Magnetic Materials and Magnetic Stimulation in Stem Cell (Neurogenic) Differentiation

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2028 - 2028

Опубликована: Янв. 19, 2023

Magnetic materials and magnetic stimulation have gained increasing attention in tissue engineering (TE), particularly for bone nervous reconstruction. Magnetism is utilized to modulate the cell response environmental factors lineage specifications, which involve complex mechanisms of action. fields nanoparticles (MNPs) may trigger focal adhesion changes, are further translated into reorganization cytoskeleton architecture an impact on nuclear morphology positioning through activation mechanotransduction pathways. Mechanical stress induced by stimuli translates elongation fibers, linker nucleoskeleton (LINC) complex, envelope deformation, finally leads mechanical regulation chromatin conformational changes. As such, internalization MNPs with promotes evolution stem cells neurogenic differentiation, triggering significant changes global gene expression that mediated histone deacetylases (e.g., HDAC 5/11), upregulation noncoding RNAs miR-106b~25). Additionally, exposure a environment had positive influence neurodifferentiation modulation calcium channels' activity cyclic AMP element-binding protein (CREB) phosphorylation. This review presents updated integrated perspective molecular govern cellular cues, special focus differentiation possible utility TE, as well limitations using magnetism these applications.

Язык: Английский

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Deciphering the dynamics: Exploring the impact of mechanical forces on histone acetylation

The FASEB Journal, Год журнала: 2024, Номер 38(15)

Опубликована: Авг. 3, 2024

Abstract Living cells navigate a complex landscape of mechanical cues that influence their behavior and fate, originating from both internal external sources. At the molecular level, translation these physical stimuli into cellular responses relies on intricate coordination mechanosensors transducers, ultimately impacting chromatin compaction gene expression. Notably, epigenetic modifications histone tails govern accessibility gene‐regulatory sites, thereby regulating Among modifications, acetylation emerges as particularly responsive to microenvironment, exerting significant control over activities. However, precise role in mechanosensing transduction remains elusive due complexity network. To address this gap, our aim is systematically explore key regulators multifaceted roles response biomechanical stimuli. In review, we initially introduce ubiquitous force experienced by then dynamic alterations its associated co‐factors, including HDACs, HATs, acetyl‐CoA, cues. Furthermore, delve interactions between mechanosensors/mechanotransducers, offering comprehensive analysis. Ultimately, review aims provide holistic understanding nuanced interplay forces within an academic framework.

Язык: Английский

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Metaboloepigenetics: Role in the Regulation of Flow-Mediated Endothelial (Dys)Function and Atherosclerosis

Cells, Год журнала: 2025, Номер 14(5), С. 378 - 378

Опубликована: Март 5, 2025

Endothelial dysfunction is the main initiating factor in atherosclerosis. Through mechanotransduction, shear stress regulates endothelial cell function both homeostatic and diseased states. Accumulating evidence reveals that epigenetic changes play critical roles etiology of cardiovascular diseases, including The metabolic regulation epigenetics has emerged as an important control gene expression states, but to best our knowledge, this connection remains largely unexplored In review, we (1) summarize how (or flow) (dys)function; (2) explore alterations occur endothelium response disturbed flow; (3) review metabolism under different conditions; (4) suggest mechanisms which may link altered epigenome by modulations metabolite availability. We believe plays role reprogramming could pave way for novel metabolism-based therapeutic strategies.

Язык: Английский

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The Dilemma of Nuclear Mechanical Forces in DNA Damage and Repair

Biochemical and Biophysical Research Communications, Год журнала: 2025, Номер unknown, С. 151639 - 151639

Опубликована: Март 1, 2025

Язык: Английский

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Changes in nuclear and actin mechanics from G1 to G2 affect nuclear integrity

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 16, 2025

Abstract The structural integrity of the nucleus is dependent on nuclear mechanical elements chromatin and lamins to resist antagonistic actin cytoskeleton forces. Imbalance results in blebbing, rupture, cellular dysfunction found many human diseases. We used Fluorescent Ubiquitin Cell Cycle Indicator (FUCCI) cells determine how cell cycle changes affect force balance. While blebs are present equally throughout interphase, form predominantly G1 then persist into G2 due increased actin-based confinement focal adhesion density vs. cells. Upon artificial confinement, nuclei ruptured more than nuclei. Single micromanipulation measurements confirmed that stronger both chromatin-based lamin-based stiffness regimes. Decreased can be explained by loss peripheral H3K9me3 from G2, recapitulated inhibition via Chaetocin. cycle-based mechanics impact shape.

Язык: Английский

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P300 Modulates Endothelial Mechanotransduction of Fluid Shear Stress

Cellular and Molecular Bioengineering, Год журнала: 2024, Номер 17(5), С. 507 - 523

Опубликована: Июнь 11, 2024

Язык: Английский

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Epigenetic Network in Immunometabolic Disease

Advanced Biology, Год журнала: 2023, Номер 8(1)

Опубликована: Окт. 4, 2023

Abstract Although a large amount of data consistently shows that genes affect immunometabolic characteristics and outcomes, epigenetic mechanisms are also heavily implicated. Epigenetic changes, including DNA methylation, histone modification, noncoding RNA, determine gene activity by altering the accessibility chromatin to transcription factors. Various factors influence these alterations, genetics, lifestyle, environmental cues. Moreover, acquired signals can be transmitted across generations, thus contributing early disease traits in offspring. A closer investigation is critical this aspect as it help understand underlying molecular further gain insights into potential therapeutic targets for preventing treating diseases arising from immuno‐metabolic dysregulation. In review, role alterations transcriptional modulation involved insulin resistance, systemic inflammation, macrophage polarization, endothelial dysfunction, metabolic cardiomyopathy, nonalcoholic fatty liver (NAFLD), discussed. An overview emerging chromatin‐modifying drugs importance individual profile personalized approaches patients with disorders presented.

Язык: Английский

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