Flow-induced reprogramming of endothelial cells in atherosclerosis

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(11), P. 738 - 753

Published: May 24, 2023

Atherosclerotic diseases such as myocardial infarction, ischaemic stroke and peripheral artery disease continue to be leading causes of death worldwide despite the success treatments with cholesterol-lowering drugs drug-eluting stents, raising need identify additional therapeutic targets. Interestingly, atherosclerosis preferentially develops in curved branching arterial regions, where endothelial cells are exposed disturbed blood flow characteristic low-magnitude oscillatory shear stress. By contrast, straight regions stable flow, which is associated high-magnitude, unidirectional stress, relatively well protected from through shear-dependent, atheroprotective cell responses. Flow potently regulates structural, functional, transcriptomic, epigenomic metabolic changes mechanosensors mechanosignal transduction pathways. A study using single-cell RNA sequencing chromatin accessibility analysis a mouse model flow-induced demonstrated that reprogrammes situ healthy phenotypes diseased ones characterized by inflammation, endothelial-to-mesenchymal transition, endothelial-to-immune cell-like transition changes. In this Review, we discuss emerging concept disturbed-flow-induced reprogramming (FIRE) potential pro-atherogenic mechanism. Defining mechanisms reprogrammed promote crucial area research could lead identification novel targets combat high prevalence atherosclerotic disease. Jo colleagues involved dysfunction atherosclerosis, including mechanism, highlight targeting flow-sensitive genes, proteins

Language: Английский

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Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 18, 2025

Gastric cancer is a highly aggressive malignancy characterized by complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are key component of the TME, exhibit significant heterogeneity and play crucial roles in progression. Therefore, comprehensive understanding CAFs essential for developing novel therapeutic strategies gastric cancer. This study investigates characteristics functional information CAF subtypes explores intercellular communication between malignant epithelial cells (ECs) analyzing single-cell sequencing data from 24 samples. CellChat was employed to map communication, Seurat used integrate with spatial transcriptome reconstruct map. The relationship apCAFs analyzed using multicolor immunohistochemistry. Cells were categorized into nine distinct categories, revealing positive correlation proportions fibroblasts. Furthermore, six fibroblast subpopulations identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle (SMCs), proliferative (pCAFs). Each these linked various biological processes immune responses. Malignant ECs exhibited heightened particularly subpopulations, through specific ligand-receptor interactions. High-density regions displayed exclusivity, pericytes serving as source iCAFs, mCAFs, apCAFs. Notably, showed increased interactions, certain pairs potentially impacting prognosis Multiplex immunohistochemistry (mIHC) confirmed close proximity Our provided characterization revealed intricate networks within TME. identified their interactions could serve potential targets.

Language: Английский

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TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy

Human Reproduction Update, Journal Year: 2024, Volume and Issue: 30(4), P. 442 - 471

Published: March 22, 2024

Abstract BACKGROUND The placenta is a unique and pivotal organ in reproduction, controlling crucial growth cell differentiation processes that ensure successful pregnancy. Placental development tightly regulated dynamic process, which the transforming factor beta (TGFβ) superfamily plays central role. This family of pleiotropic factors heavily involved regulating various aspects reproductive biology, particularly trophoblast during first trimester TGFβ signalling precisely regulates invasion transition from cytotrophoblasts to extravillous trophoblasts, an epithelial-to-mesenchymal transition-like process. Later pregnancy, ensures proper vascularization angiogenesis placental endothelial cells. Beyond its role trophoblasts cells, contributes polarization function decidual macrophages by promoting maternal tolerance semi-allogeneic foetus. Disturbances early have been associated with several pregnancy complications, including preeclampsia (PE) one severe complications. Emerging evidence suggests pathogenesis PE, thereby offering potential target for intervention human placenta. OBJECTIVE AND RATIONALE comprehensive review aims explore elucidate roles major members superfamily, TGFβs, bone morphogenetic proteins (BMPs), activins, inhibins, nodals, (GDFs), context function. focusses on their interactions within types placenta, namely immune both normal pregnancies complicated PE throughout SEARCH METHODS A literature search was carried out using PubMed Google Scholar, searching terms: ‘TGF preeclampsia’, ‘pregnancy TGF signalling’, ‘preeclampsia tgfβ’, bmp’, gdf’, activin’, ‘endoglin pregnancy’, ‘tgfβ ‘bmp ‘gdf ‘activin ‘Hofbauer tgfβ ‘placental ‘endothelial cells ‘endothelium ‘trophoblast Smad’, development’, ‘TGFβ function’, dysfunction ‘vascular remodelling TGFβ’, ‘inflammation ‘immune response NK cells’, tregs’, ‘NK ‘Tregs preeclampsia’. Only articles published English until 2023 were used. OUTCOMES understanding interconnected functions main provides valuable insights into essential foetus By orchestrating invasion, vascularization, tolerance, tissue remodelling, ligands contribute functioning healthy maternal–foetal interface. However, dysregulation has implicated where shallow defective vascular decreased uteroplacental perfusion, observed are all affected altered signalling. WIDER IMPLICATIONS important implications research clinical practice. Further investigation required understand underlying mechanisms, different regulation under pathophysiological conditions, order discover new therapeutic targets. Distinguishing between clinically manifested subtypes studying holistically step. To put this knowledge practice, pre-clinical animal models combined technologies needed. may also lead improved identify targets, ultimately improving outcomes reducing burden PE.

Language: Английский

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Neuroprotective effects of phytochemicals through autophagy modulation in ischemic stroke

Inflammopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Language: Английский

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The placenta: epigenetic insights into trophoblast developmental models of a generation-bridging organ with long-lasting impact on lifelong health

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(4), P. 2523 - 2560

Published: May 12, 2023

The placenta is a unique organ system that functionally combines both maternal and fetal cell types with distinct lineage origins. Normal placentation critical for developmental progression reproductive success. Although the best known its nutrient supply function to fetus, genetic experiments in mice highlight also pivotal directing proper formation of specific organs. These roles underscore importance pregnancy outcome lifelong health span, which makes it essential better understand molecular processes governing placental development find adequate models study it. In this review, we provide an overview instructional role epigenome dictating fate decisions specifically trophoblast lineage. We then focus on recent advances exploring stem organoid reflecting feto-maternal interface humans much-improved tools events early development. discuss cells derived from as well those artificially induced resemble placenta, how they can be combined embryonic endometrial uterus reconstitute implantation site. allude exciting prospects these harnessed biomedicine enhance our understanding pathological underpinnings complications patient-specific manner, ultimately facilitate therapeutic approaches tissue- organ-based regenerative medicine.

Language: Английский

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A spatiotemporal transcriptomic atlas of mouse placentation

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 22, 2024

Language: Английский

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Profiling the cell-specific small non-coding RNA transcriptome of the human placenta

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

The human placenta is the composite of multiple cell types, each which contributes uniquely to placental function. Small non-coding RNAs (sncRNAs) are regulators gene expression and can be cell-specific. sncRNA transcriptome individual types has not yet been investigated due difficulties in their procurement isolation. Using a custom sequencing method, we explored seven species (miRNA, piRNA, rRNA, scaRNA, snRNA, snoRNA, tRNA) from whole chorionic villi four major sample-matched FACS-sorted type (cytotrophoblast, stromal, endothelial, Hofbauer) samples 9 first trimester 17 term placentas. After normalization for technical variables, clustered primarily by lineage. No sncRNAs were expressed type, however, mean differed 115 sncRNAs. Known placentally-expressed showed differing trimester. Expression few varied sex. Lastly, DNA methylation correlation was significant, although high (> R 2 ± 0.6) observed some sncRNA-CpG pairs. This study represents exploration bulk informing about regulatory patterns underlying development.

Language: Английский

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Extracellular Vesicles Alter Trophoblast Function in Pregnancies Complicated by COVID‐19

Journal of Extracellular Vesicles, Journal Year: 2025, Volume and Issue: 14(4)

Published: April 1, 2025

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and resulting disease (COVID‐19) cause placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal pathology from COVID‐19 is common, direct placenta rare. This suggests that pathophysiology associated with maternal COVID‐19, rather than infection, responsible for dysfunction. We hypothesized circulating extracellular vesicles (EVs), altered by during pregnancy, contribute to To examine this hypothesis, we characterized EVs pregnancies complicated tested their effects on trophoblast cell physiology in vitro. Trophoblast exposure isolated patients an active (AI), but not controls, key functions including hormone production invasion. Thus, participants AI, both symptomatic asymptomatic cases, can disrupt vital functions. EV cargo differed between depending gestational timing Controls, may disruption transcriptome morphology. Our findings show have throughout EVs, are likely participate dysfunction induced COVID‐19.

Language: Английский

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IMMUNOHISTOCHEMICAL FEATURES OF BAX-DEPENDENT APOPTOSIS IN THE TROPHOBLAST OF PLACENTAL CHOROIDAL VILLI AT DELIVERY AFTER 40 WEEKS

Eastern Ukrainian Medical Journal, Journal Year: 2025, Volume and Issue: 13(1), P. 285 - 292

Published: Jan. 1, 2025

The relevance of studying the molecular mechanisms that regulate apoptosis in placental tissues, especially later stages pregnancy, is significant for understanding this organ's normal and pathological functioning. Apoptosis, or programmed cell death, essential maintaining tissue homeostasis, ensuring function, adequate metabolism between mother fetus. One main proteins BAX – a molecule actively involved initiation process through activation caspases. study aimed to determine features BAX-dependent trophoblast chorionic villi by immunohistochemical method at delivery after 40 weeks. Materials methods: material (pieces from intermediate zone fetal plate basal plate) was fixed 22–24 hours neutral buffered (Lilly) 10% aqueous formalin solution. Then, dehydrated an ascending alcohol series (from 50 degrees “absolute” alcohol) embedded paraffin 58 °C. Histological serial sections 5 μm thickness were obtained on sledge microtome MS-2. After deparaffinization histological sections, hematoxylin eosin staining performed, techniques used other accordance with manufacturer’s protocols (DAKO). In particular, reactions primary antibodies against pro-apoptotic protein anti-apoptotic Bcl-2 performed. Visualization carried out using polymeric system visualize reaction results diaminobenzidine dye (it gives clear brown color locations studied antigens). Along descriptive histopathological examination, we also performed computer morphometry previously digital copies optical microscopic images (Delta Optical Evolution 100 microscope planachromatic objectives required magnification Olympus SP550UZ camera adapter). Digital image analyzed legal copy ImageJ v1.53t program, specialized histometric studies. eosin-stained subjected scoring test (repeated counting, which provides data proportion “syncytial nodules”). assessed specific intensity computerized microdensitometry. To do this, built-in standard tools program obtain value brightness 8-bit analysis (with gradation zero 255) microprobe method. Further, converted relative density (in units) logarithmic transformation. way convenient interpreting as it ranged (absolute transparency) one opacity). processed statistical methods. help calculations PAST v 4.17, preliminary normality distribution Shapiro–Wilk test. According criterion, hypothesis not rejected (at p=0.05) all samples; thus, parametric methods used: calculation arithmetic mean its error, unpaired two-sided Student's addition test, non-parametric Mann–Whitney used, but significance reported only Results: Thus, point view regulation weeks vs. physiological pregnancy delivery, conditions are created enhanced death apoptosis, since there increase concentration BAX-protein, while antagonist, Bcl-2, decreases markedly. Conclusions: At weeks, processes activated trophoblast, syncytial nodules increases accordingly.

Language: Английский

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The maternal-fetal interface at single-cell resolution: uncovering the cellular anatomy of the placenta and decidua

American Journal of Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: 232(4), P. S55 - S79

Published: April 1, 2025

Language: Английский

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