Piezo1 Channel Activation Reverses Pulmonary Artery Vasoconstriction in an Early Rat Model of Pulmonary Hypertension: The Role of Ca2+ Influx and Akt-eNOS Pathway

Ribeiro, Thais Porto; Barbeau, Solène; Baudrimont, Isabelle; Vacher, Pierre; Freund-Michel, Véronique; Cardouat, Guillaume; Berger, Patrick; Guibert, Christelle; Ducret, Thomas; Quignard, Jean-François

doi:10.3390/cells11152349

Cited by 15 publications

(8 citation statements)

References 47 publications

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“…This suggests that other mechanoreceptors are responsible for flow mediated vasodilation in the pulmonary circulation. In support of this, evidence has been presented more recently that Piezo1 channels activate flow mediated vasodilatation in the pulmonary circulation (Lhomme, Gilbert et al 2019, Porto Ribeiro, Barbeau et al 2022).…”

Section: Discussionmentioning

confidence: 83%

Shear stress-induced restoration of pulmonary endothelial barrier function following ischaemia reperfusion injury requires VEGFR2 signalling

Walsh,

Kostyunina,

Boylan

et al. 2024

Preprint

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Normal physiological shear stress produced by blood flow is sensed by the vascular endothelium and required for the maintenance of both the normal structure and barrier function of the endothelium. Many common, critical illnesses are characterised by periods of abnormally reduced or absent shear stress e.g. haemorrhagic shock, myocardial infarction and pulmonary embolism and are complicated by oedema formation following restoration of normal perfusion (IRI).We tested the hypothesis that, in lungs injured by a period of ischaemia and reperfusion (IRI), reduced shear stress contributes to increased endothelial barrier permeability and oedema formation following the restoration of perfusion. Furthermore, we examined the role of VEGFR2 as a mechanosensor in the response of the pulmonary endothelium to altered shear stress in this condition.Following IRI, we perfused isolated ventilated mouse lungs with a low viscosity solution (LVS) or a higher, physiological viscosity solution (PVS) at constant flow to produce differing shear stresses on the endothelium of the intact pulmonary circulation. Lungs perfused with LVS developed pulmonary oedema due to increased endothelial permeability whereas those perfused with PVS were protected from oedema formation by reduced endothelial permeability. This effect of PVS required normal VEGFR2 tyrosine kinase activity but was unaffected by blocking VEGFA binding to the receptor.These data show for the first time that shear stress has an important role in restoring endothelial barrier function in the pulmonary circulation following injury and have important implications for the treatment of pulmonary oedema in critically ill patients following ischaemia reperfusion injury.

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Section: Discussionmentioning

confidence: 83%

Shear stress-induced restoration of pulmonary endothelial barrier function following ischaemia reperfusion injury requires VEGFR2 signalling

Walsh,

Kostyunina,

Boylan

et al. 2024

Preprint

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“…Previous studies reported the blockade of piezo1 by ruthenium red and gadolinium [ 19 , 20 , 21 ]. When cells were exposed to Yoda1 in the presence of 50 µM ruthenium red, the Yoda1-induced increased Rb uptake response was abolished ( Figure 7 A).…”

Section: Resultsmentioning

confidence: 99%

Activation of Piezo1 Increases Na,K-ATPase-Mediated Ion Transport in Mouse Lens

Shahidullah

Rosales

Delamere

2022

IJMS

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Lens ion homeostasis depends on Na,K-ATPase and NKCC1. TRPV4 and TRPV1 channels, which are mechanosensitive, play important roles in mechanisms that regulate the activity of these transporters. Here, we examined another mechanosensitive channel, piezo1, which is also expressed in the lens. The purpose of the study was to examine piezo1 function. Recognizing that activation of TRPV4 and TRPV1 causes changes in lens ion transport mechanisms, we carried out studies to determine whether piezo1 activation changes either Na,K-ATPase-mediated or NKCC1-mediated ion transport. We also examined channel function of piezo1 by measuring calcium entry. Rb uptake was measured as an index of inwardly directed potassium transport by intact mouse lenses. Intracellular calcium concentration was measured in Fura-2 loaded cells by a ratiometric imaging technique. Piezo1 immunolocalization was most evident in the lens epithelium. Potassium (Rb) uptake was increased in intact lenses as well as in cultured lens epithelium exposed to Yoda1, a piezo1 agonist. The majority of Rb uptake is Na,K-ATPase-dependent, although there also is a significant NKCC-dependent component. In the presence of ouabain, an Na,K-ATPase inhibitor, Yoda1 did not increase Rb uptake. In contrast, Yoda1 increased Rb uptake to a similar degree in the presence or absence of 1 µM bumetanide, an NKCC inhibitor. The Rb uptake response to Yoda1 was inhibited by the selective piezo1 antagonist GsMTx4, and also by the nonselective antagonists ruthenium red and gadolinium. In parallel studies, Yoda1 was observed to increase cytoplasmic calcium concentration in cells loaded with Fura-2. The calcium response to Yoda1 was abolished by gadolinium or ruthenium red. The calcium and Rb uptake responses to Yoda1 were absent in calcium-free bathing solution, consistent with calcium entry when piezo1 is activated. Taken together, these findings point to stimulation of Na,K-ATPase, but not NKCC, when piezo1 is activated. Na,K-ATPase is the principal mechanism responsible for ion and water homeostasis in the lens. The functional role of lens piezo1 is a topic for further study.

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“…It has been reported that PIEZO1 is upregulated in pulmonary arterial ECs during pulmonary hypertension, 76 and pharmacological manipulation of its activity has been reported to modulate vascular defects induced in models of vascular calcification, 77 hyperglycemia, 78 and pulmonary hypertension. 79 Moreover, PIEZO1 is directly involved in atherosclerosis, 54 a common condition corresponding to a slowly worsening chronic inflammatory disease (Figure 3B). Atherosclerosis occurs preferentially in branches and curves in arteries exposed to disturbed blood flow inducing inflammation, endothelialmesenchymal transition, thrombosis, vasoconstriction, and barrier dysfunction.…”

Section: Pathogenic Effects Of Endothelial Piezo1 Activity Under Dist...mentioning

confidence: 99%

PIEZO Ion Channels in Cardiovascular Functions and Diseases

Coste,

Delmas

2024

Circulation Research

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The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after mechanosensitive excitatory channels involved in touch and proprioception in mammals. However, more and more pieces of evidence point to the importance of PIEZO channels in cardiovascular activities and disease development. PIEZO channel-related cardiac functions include transducing hemodynamic forces in endothelial and vascular cells, red blood cell homeostasis, platelet aggregation, and arterial blood pressure regulation, among others. PIEZO channels contribute to pathological conditions including cardiac hypertrophy and pulmonary hypertension and congenital syndromes such as generalized lymphatic dysplasia and xerocytosis. In this review, we highlight recent advances in understanding the role of PIEZO channels in cardiovascular functions and diseases. Achievements in this quickly expanding field should open a new road for efficient control of PIEZO-related diseases in cardiovascular functions.

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Piezo1 Channel Activation Reverses Pulmonary Artery Vasoconstriction in an Early Rat Model of Pulmonary Hypertension: The Role of Ca2+ Influx and Akt-eNOS Pathway

Cited by 15 publications

References 47 publications

Shear stress-induced restoration of pulmonary endothelial barrier function following ischaemia reperfusion injury requires VEGFR2 signalling

Shear stress-induced restoration of pulmonary endothelial barrier function following ischaemia reperfusion injury requires VEGFR2 signalling

Activation of Piezo1 Increases Na,K-ATPase-Mediated Ion Transport in Mouse Lens

PIEZO Ion Channels in Cardiovascular Functions and Diseases

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