The Unexpected Role of the Endothelial Nitric Oxide Synthase at the Neurovascular Unit: Beyond the Regulation of Cerebral Blood Flow DOI Open Access
Giorgia Scarpellino,

Valentina Brunetti,

Roberto Berra‐Romani

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9071 - 9071

Published: Aug. 21, 2024

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then exert tight control over much broader range of processes, including neurotransmitter release, neuronal excitability, synaptic plasticity. Endothelial NO synthase (eNOS) usually far from the mind neurophysiologists, who have focused most their attention on (nNOS) as primary source at neurovascular unit (NVU). Nevertheless, available evidence suggests eNOS could also contribute generating burst that, serving volume intercellular messenger, produced in response activity brain parenchyma. Herein, we review role both regulation cerebral blood flow plasticity discuss mechanisms by which cerebrovascular endothelial cells may transduce inputs into signal. We further suggest play critical vascular-to-neuronal communication integrating signals converging onto streaming active neurons.

Language: Английский

Vascular mechanotransduction DOI
Michael J. Davis, Scott Earley,

Yi‐Shuan Li

et al.

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(2), P. 1247 - 1421

Published: Jan. 5, 2023

This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial (ECs), including their sensing mechanical stimuli transduction signals that result acute functional modulation longer-term transcriptomic epigenetic regulation blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures receptors, junction proteins. mechanosignaling pathways presented cytoskeleton, integrins, extracellular matrix, intracellular signaling molecules. These are followed by discussions on transcriptome epigenetics, relevance health disease, interactions between VSMCs ECs. Throughout this review, we offer suggestions for specific topics require further understanding. In closing section conclusions perspectives, summarize what is known point out need treat vasculature as a system, not only ECs but also matrix other types such resident macrophages pericytes, so can fully understand physiology pathophysiology vessel whole, thus enhancing comprehension, diagnosis, treatment, prevention diseases.

Language: Английский

Citations

114
Blood pressure pulsations modulate central neuronal activity via mechanosensitive ion channels DOI
Luna Jammal, Sebastian H. Bitzenhofer, Ileana L. Hanganu‐Opatz

et al.

Science, Journal Year: 2024, Volume and Issue: 383(6682)

Published: Feb. 1, 2024

The transmission of the heartbeat through cerebral vascular system causes intracranial pressure pulsations. We discovered that arterial pulsations can directly modulate central neuronal activity. In a semi-intact rat brain preparation, elicited correlated local field oscillations in olfactory bulb mitral cell layer. These did not require synaptic but reflected baroreceptive transduction cells. This was mediated by fast excitatory mechanosensitive ion channel and modulated spiking awake animals, entrained activity subset neurons within ~20 milliseconds. Thus, we propose this fast, intrinsic interoceptive mechanism perception-for example, during arousal-within possibly across various other areas.

Language: Английский

Citations

61
PIEZO1 and PECAM1 interact at cell-cell junctions and partner in endothelial force sensing DOI Creative Commons
Eulashini Chuntharpursat‐Bon, Oleksandr V. Povstyan, Melanie J. Ludlow

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: April 1, 2023

Abstract Two prominent concepts for the sensing of shear stress by endothelium are PIEZO1 channel as a mediator mechanically activated calcium ion entry and PECAM1 cell adhesion molecule apex triad with CDH5 VGFR2. Here, we investigated if there is relationship. By inserting non-disruptive tag in native mice, reveal situ overlap PECAM1. Through reconstitution high resolution microscopy studies show that interacts directs it to cell-cell junctions. extracellular N-terminus critical this, but C-terminal intracellular domain linked also contributes. similarly drives junctions unlike its interaction dynamic, increasing stress. does not interact required Ca 2+ -dependent formation adherens associated cytoskeleton, consistent conferring force-dependent junctional remodelling. The data suggest pool at junctions, coming together mechanisms intimate cooperation molecules tailoring structure mechanical requirement.

Language: Английский

Citations

51
Mechanisms of mechanotransduction and physiological roles of PIEZO channels DOI
Bailong Xiao

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Language: Английский

Citations

28
Oxidative stress and ion channels in neurodegenerative diseases DOI Creative Commons
Razan Orfali,

Adnan Z. Alwatban,

Rawan S. Orfali

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 29, 2024

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of channels. Abundant associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington’s disease. Reactive oxygen nitrogen species compounds trigger posttranslational alterations that target specific sites within subunits responsible for assembly. These include adjustment cysteine residues through reactions induced by reactive (ROS), nitration, S-nitrosylation assisted nitric oxide tyrosine peroxynitrite. Several channels directly investigated their functional responses to oxidizing agents stress. This review primarily explores relationship potential links between in conditions, such as cerebellar ataxias Parkinson’s correlation could hold promise developing innovative therapies common diseases.

Language: Английский

Citations

23
Piezo1 as a force-through-membrane sensor in red blood cells DOI Creative Commons
George Vaisey, Priyam Banerjee, Alison J. North

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 14, 2022

Piezo1 is the stretch activated Ca

Language: Английский

Citations

40
Mechanosensing by Vascular Endothelium DOI Creative Commons
Xin Rui Lim, Osama F. Harraz

Annual Review of Physiology, Journal Year: 2023, Volume and Issue: 86(1), P. 71 - 97

Published: Oct. 20, 2023

Mechanical forces influence different cell types in our bodies. Among the earliest experienced mammals is blood movement vascular system. Blood flow starts at embryonic stage and ceases when heart stops. exposes endothelial cells (ECs) that line all vessels to hemodynamic forces. ECs detect these mechanical (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes diameter. In this review, we focus on mechanosensing how ion channels, receptors, membrane structures mediate intricate mechanotransduction responses. We further highlight often reflect collaborative efforts involving several mechanosensors mechanotransducers. close with a consideration of current knowledge regarding dysregulation during disease. Because disruptions are hallmarks cardiovascular disease, studying holds great promise for advancing understanding physiology pathophysiology.

Language: Английский

Citations

33
Mitochondrial oxidative stress in brain microvascular endothelial cells: Triggering blood-brain barrier disruption DOI Creative Commons

Yi Wang,

Jing Wu, Jiexin Wang

et al.

Mitochondrion, Journal Year: 2023, Volume and Issue: 69, P. 71 - 82

Published: Jan. 26, 2023

Blood-brain barrier disruption plays an important role in central nervous system diseases. This review provides information on the of mitochondrial oxidative stress brain microvascular endothelial cells cellular dysfunction, intercellular junctions, transporter abnormal angiogenesis, neurovascular decoupling, and involvement aggravation vascular inflammation illustrates related molecular mechanisms. In addition, recent drug nondrug therapies targeting cerebral cell mitochondria to repair blood–brain are discussed. shows that disorder a key occurrence development damage may be critical various pathological mechanisms damage. These new findings suggest potential strategy for treatment diseases through modulation cells.

Language: Английский

Citations

30
Piezo1-dependent regulation of pericyte proliferation by blood flow during brain vascular development DOI Creative Commons

Huaxing Zi,

Xiaolan Peng, Jianbin Cao

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(1), P. 113652 - 113652

Published: Jan. 1, 2024

Blood flow is known to regulate cerebrovascular development through acting on vascular endothelial cells (ECs). As an indispensable component of the neurovascular unit, brain pericytes physically couple with ECs and play vital roles in blood-brain barrier integrity maintenance coupling. However, it remains unclear whether blood affects pericyte development. Using vivo time-lapse imaging larval zebrafish, we monitored developmental dynamics found that they proliferate expand their population increase coverage vessels. In combination pharmacological genetic approaches, demonstrated enhances proliferation Piezo1 expressed ECs. Moreover, identified EC-intrinsic Notch signaling downstream promote activation pericytes. Thus, our findings reveal a role proliferation, extending functional spectrum hemodynamics

Language: Английский

Citations

13
Capillary malformations DOI Creative Commons
Adrienne M. Hammill, Elisa Boscolo

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(8)

Published: April 14, 2024

Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with CM localized on the forehead have an increased risk developing neurocutaneous disorder called encephalotrigeminal angiomatosis Sturge-Weber syndrome (SWS), complications including seizure, developmental delay, glaucoma, and vision loss. In 2013, groundbreaking study revealed causative activating somatic mutations gene (GNAQ) encoding guanine nucleotide-binding protein Q subunit α (Gαq) SWS patient tissues. this Review, we discuss disease phenotype, GNAQ mutations, their cellular origin. We also present endothelial Gαq-related signaling pathways, current animal models to its complications, future options for therapeutic treatment. Further work remains fully elucidate molecular mechanisms underlying formation maintenance abnormal vessels.

Language: Английский

Citations

10