Unraveling the deadly dance: endothelial cells and neutrophils in sepsis-induced acute lung injury/acute respiratory distress syndrome DOI Creative Commons

Xiujuan Xu,

Qi Zhang, Zheng Lv

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: May 22, 2025

Sepsis-induced acute lung injury (ALI) and respiratory distress syndrome (ARDS) are severe complications with high morbidity mortality rates, characterized primarily by diffuse alveolar damage, endothelial dysfunction, local inflammatory responses. Neutrophils cells (ECs) play crucial roles in the pathogenesis progression of these diseases. important regulators inflammation, while dysfunction exacerbates vascular permeability cascade. The interaction between neutrophils ECs is vital for development ALI/ARDS induced sepsis, driving pathological processes inflammation tissue damage. Despite advancements treatment strategies such as protective mechanical ventilation fluid management, effective methods rapid recovery or significant improvement outcomes remain lacking. Therefore, we comprehensively summarize current literature to gain deeper insights into neutrophils, ECs, their interactions sepsis-induced ALI/ARDS, hoping provide critical mechanisms underlying sepsis-related potential pathways developing new therapeutic approaches.

Language: Английский

The pathobiology of neurovascular aging DOI
Monica M. Santisteban, Costantino Iadecola

Neuron, Journal Year: 2025, Volume and Issue: 113(1), P. 49 - 70

Published: Jan. 1, 2025

Language: Английский

Citations

3
Swimming motions evoke Ca2+events in vascular endothelial cells of larval zebrafish via mechanical activation of Piezo1 DOI Creative Commons
Bill Jia, Xin Tang, Marlies P. Rossmann

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Summary Calcium signaling in blood vessels regulates their growth 1,2 , immune response 3 and vascular tone 4 . Vascular endothelial cells are known to be mechanosensitive 5–7 it has been assumed that this mechanosensation mediates calcium responses pulsatile flow 8–10 Here we show larval zebrafish, the dominant trigger for Ca 2+ events comes from body motion, not heartbeat-driven flow. Through a series of pharmacological mechanical perturbations, showed motion is necessary sufficient induce events, while neither neural activity nor circulation either or sufficient. Knockout temporally restricted knockdown piezo1 eliminated motion-induced events. Our results demonstrate swimming-induced tissue an important driver dynamics zebrafish. Highlights Swimming motions zebrafish evoke large, rapid, pervasive transients cells. These do require firing, muscular electrical activity, endocrine factors, heart-driven Mechanical forces transients. Endothelial ion channel Piezo1.

Language: Английский

Citations

1
Endothelial TRPV4–Cx43 signalling complex regulates vasomotor tone in resistance arteries DOI Creative Commons
Pía C. Burboa, Pablo S. Gaete, Ping Shu

et al.

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Abstract S ‐nitrosylation of Cx43 gap junction channels critically regulates communication between smooth muscle cells and endothelial cells. This post‐translational modification also induces the opening undocked hemichannels. However, its specific impact on vasomotor regulation remains unclear. Considering role TRPV4 channel activation in promoting vasodilatation through nitric oxide (NO) production, we investigated direct modulation hemichannels by activation. Using proximity ligation assay, identified that are found close endothelium resistance arteries. In primary cell (EC) cultures from arteries, GSK 1016790A‐induced enhances eNOS activity, increases NO opens via ‐nitrosylation. Notably, elevated intracellular Ca 2+ levels caused were reduced blocking ex vivo mesenteric inhibiting hyperpolarization without affecting production ECs, underscoring a critical TRPV4–Cx43 signalling electrical behaviour. We perturbed Cx43/TRPV4 disrupting lipid rafts ECs using β‐cyclodextrin. Under these conditions, hemichannel influx blunted upon stimulation. Intravital microscopy arterioles further demonstrated integrity reduce TRPV4‐induced relaxation. These findings underscore new pivotal associated with pathway modulating behaviour tone regulation. image Key points TRPV4‐Cx43 interaction cells: study reveals proteins establishing functional is for vascular hemichannels: treatment Cx43, facilitating TRPV4‐mediated calcium signalling: leads to increased cells, an effect mitigated inhibition hemichannels, indicating regulatory feedback mechanism two channels. Endothelial regulation: Blocking impairs suggesting contributing vasodilatation. vasodilatation: intravital mouse activity significantly impair vasodilatation, highlighting crucial regulating function

Language: Английский

Citations

1
Cognitive Impairment and Synaptic Dysfunction in Cardiovascular Disorders: The New Frontiers of the Heart–Brain Axis DOI Creative Commons
Teresa Soda, Teresa Pasqua, Giovambattista De Sarro

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2387 - 2387

Published: Oct. 18, 2024

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in strength. This plasticity often manifests as long-term potentiation (LTP) depression (LTD), which are bidirectional modulations of efficacy. Strong epidemiological experimental evidence show that heart-brain axis could be severely compromised both neurological cardiovascular disorders. Particularly, disorders, such heart failure, hypertension, obesity, diabetes insulin resistance, arrhythmias, may lead cognitive impairment, a condition known cardiogenic dementia. Herein, we review available knowledge on molecular mechanisms dementia arise describe how LTP and/or LTD induction maintenance CA1 region hippocampus metabolic syndrome, arrhythmias. We also discuss emerging endothelial dysfunction contribute directly altering hippocampal impairing synaptically induced activation nitric oxide synthase. A better understanding CV disorders impact proper function synapses will shed novel light underpinnings dementia, thereby providing new perspective for more specific pharmacological treatments.

Language: Английский

Citations

7
Pericyte Electrical Signalling and Brain Haemodynamics DOI Creative Commons
Thomas A. Longden, Dominic Isaacs

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2025, Volume and Issue: 136(5)

Published: March 30, 2025

ABSTRACT Dynamic control of membrane potential lies at the nexus a wide spectrum biological processes, ranging from individual cell secretions to orchestration complex thought and behaviour. Electrical signals in all vascular types (smooth muscle cells, endothelial cells pericytes) contribute haemodynamics energy delivery across spatiotemporal scales throughout tissues. Here, our goal is review synthesize key studies electrical signalling within brain vasculature integrate these with recent data illustrating an important role for pericytes, doing so attempting work towards holistic description blood flow by signalling. We use this as framework generating further questions that we believe are pursue. Drawing parallels signal integration nervous system may facilitate deeper insights into how organized it controls network level.

Language: Английский

Citations

0
Endothelial Piezo1 stimulates angiogenesis to offer protection against intestinal ischemia–reperfusion injury in mice DOI Creative Commons

Cuifen Wang,

Shangfei Luo,

Yameng Yan

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 22, 2025

Abstract Background Intestinal ischemia–reperfusion (I/R) injury, which occurs in the ileum and not only leads to intestinal tissue damage, but also may trigger systemic inflammatory responses, is a prevalent pathological condition that typically associated with acute ischemia, surgical procedures, or trauma. However, precise underlying pathogenic mechanisms have yet been fully uncovered. In this study, we explored specific roles by endothelial Piezo1 involved I/R injury. Methods We evaluated of using both vivo mouse injury vitro hypoxia-reoxygenation (H/R) models. The expression was assessed immunofluorescence RT-qPCR. experiments involving knockout activation agonist Yoda1 were conducted observe effects on angiogenesis Results found post-intestinal mice, markedly increased mainly abundant cells. Specific exhibited more severe phenotype characterized accelerating damage structure, increasing response, inhibiting angiogenesis. Yoda1-mediated significantly ameliorated Activation induced H/R promoted Human Umbilical Vein Endothelial Cells (HUVECs), inhibited GsMTx4. mediated linked an increase extracellular Ca 2+ influx, turn enhanced hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway. Conclusions Our findings indicate plays crucial role protecting against promoting cells, possibly through /HIF-1α/VEGF This suggests targeting channels could be therapeutic strategy for

Language: Английский

Citations

0
Non-invasive therapeutics for neurotrauma: a mechanistic overview DOI Creative Commons
James D. O’Leary, Bevan S. Main, Mark P. Burns

et al.

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: May 14, 2025

Traumatic brain injury is a leading cause of death and major risk factor for the development both memory motor disorders. To date, there are no proven interventions to improve patient outcome after neurotrauma. A promising avenue treatment has emerged in use non-invasive therapies recovery injury. number stimulation techniques have been developed, such as transcranial direct current stimulation, magnetic vagus nerve well low intensity ultrasound photobiomodulation therapy. However, standardized regimens not developed. There clear need better understand underlying mechanisms therapeutics on pathology so more effectively guide strategy. Here we review literature preclinical neurotrauma offer insight into potential mechanism action novel targets traumatic

Language: Английский

Citations

0
Unraveling the deadly dance: endothelial cells and neutrophils in sepsis-induced acute lung injury/acute respiratory distress syndrome DOI Creative Commons

Xiujuan Xu,

Qi Zhang, Zheng Lv

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: May 22, 2025

Sepsis-induced acute lung injury (ALI) and respiratory distress syndrome (ARDS) are severe complications with high morbidity mortality rates, characterized primarily by diffuse alveolar damage, endothelial dysfunction, local inflammatory responses. Neutrophils cells (ECs) play crucial roles in the pathogenesis progression of these diseases. important regulators inflammation, while dysfunction exacerbates vascular permeability cascade. The interaction between neutrophils ECs is vital for development ALI/ARDS induced sepsis, driving pathological processes inflammation tissue damage. Despite advancements treatment strategies such as protective mechanical ventilation fluid management, effective methods rapid recovery or significant improvement outcomes remain lacking. Therefore, we comprehensively summarize current literature to gain deeper insights into neutrophils, ECs, their interactions sepsis-induced ALI/ARDS, hoping provide critical mechanisms underlying sepsis-related potential pathways developing new therapeutic approaches.

Language: Английский

Citations

0