Stretch-activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries

Lhomme, Audrey; Gilbert, Guillaume; Pelé, Thomas; Deweirdt, Juliette; Henrion, Didier; Baudrimont, Isabelle; Campagnac, Marilyne; Marthan, Roger; Guibert, Christelle; Ducret, Thomas; Savineau, Jean‐Pierre; Quignard, Jean-François

doi:10.1165/rcmb.2018-0197oc

Cited by 49 publications

(41 citation statements)

References 36 publications

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“…It might be surprising that activation of endothelial Piezo1 channels can cause both vasodilation 7,31,32,34 and vasoconstriction 21 and that endothelial-specific Piezo1 disruption can both elevate resting systolic blood pressure 7 and blunt elevated diastolic and systolic blood pressure caused by whole-body physical activity. 21 However, Piezo1 presents an intriguing dichotomy for endothelial cells because it forms a Ca 2+ -permeable nonselective cationic channel.…”

Section: Challenges and Controversiesmentioning

confidence: 99%

Force Sensing by Piezo Channels in Cardiovascular Health and Disease

Beech

Kalli

2019

ATVB

172

153

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Mechanical forces are fundamental in cardiovascular biology, and deciphering the mechanisms by which they act remains a testing frontier in cardiovascular research. Here, we raise awareness of 2 recently discovered proteins, Piezo1 and Piezo2, which assemble as transmembrane triskelions to combine exquisite force sensing with regulated calcium influx. There is emerging evidence for their importance in endothelial shear stress sensing and secretion, NO generation, vascular tone, angiogenesis, atherosclerosis, vascular permeability and remodeling, blood pressure regulation, insulin sensitivity, exercise performance, and baroreceptor reflex, and there are early suggestions of relevance to cardiac fibroblasts and myocytes. Human genetic analysis points to significance in lymphatic disease, anemia, varicose veins, and potentially heart failure, hypertension, aneurysms, and stroke. These channels appear to be versatile force sensors, used creatively to inform various force-sensing situations. We discuss emergent concepts and controversies and suggest that the potential for new important understanding is substantial.

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Section: Challenges and Controversiesmentioning

confidence: 99%

Force Sensing by Piezo Channels in Cardiovascular Health and Disease

Beech

Kalli

2019

ATVB

172

153

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“…Stretch-activated channel (SAC) was initially discovered in skeletal muscle cells by Guharay , [ 20 ] and subsequent studies have shown that SAC is widely present in various cell s[ 21 ]. Qiu found that mechanical tension stimulates the SAC signaling pathway and regulates the expression of corresponding mRNAs and proteins in a rat aortic dissection mode l[ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α

Huang

Liu

Pan

et al. 2021

J Cardiothorac Surg

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Background This study aimed to explore whether the mechanical stretching-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in pulmonary veins occurred through the stretch-activated channel (SAC)/ mitogen-activated protein kinases (MAPKs) pathway. Methods Sixty male Sprague-Dawley rats were divided into three sham groups and seven model groups. A metal clip was placed on the ascending aorta in the model group to establish PH-LHD rat model. The sham group received a similar operation without ascending aorta clamped. On day 25, pulmonary vein was given mechanical stretching with 0 g, 2.0 g tension in two model groups and two sham groups. Another four model groups were given 2.0 g tension after MAPKs pathway inhibitors soaked. The last sham group and model group rats’ pulmonary veins, pulmonary artery and lung tissues were obtained on day 35. Pulmonary vein, pulmonary artery and lung tissue were evaluated by echocardiography, HE staining, immunohistochemistry and western blotting respectively. Results On day 25, left heart weight, right ventricular pressure (35.339 cmH2O) and left atrial pressure (13.657 cmH2O) were increased in model group than those in sham group. Echocardiography showed left heart failure in the PH-LHD group (Interventrieular septum dimension 1.716 mm, left ventricular internal end diastolic dimension 4.888 mm, left ventricular posterior wall thickness in diastole 1.749 mm, ejection fraction 76.917%). But there was no difference in lung tissue between the sham group and PH-LHD group as showed by HE staining. Our results showed that the expression of IL-6 and TNF-α was highly expressed in PH-LHD rats’ serum and pulmonary vein, which were further increased after 2.0 g tension was given and were decreased after SAC/MAPKs inhibitors treatment. Meanwhile, on day 25, immunohistochemistry analysis showed the expression of IL-6 and TNF-α was higher in the PH-LHD rats’ pulmonary vein than that in pulmonary artery and lung tissue, and these expressions in pulmonary vein of PH-LHD group were also higher than that in sham group. However, on day 35, IL-6 and TNF-α were all increased in the pulmonary veins, arteries and lung tissues. Besides, our results uncovered that SAC/MAPKs pathway were upregulating in PH-LHD rats’ pulmonary vein. Conclusion In conclusion, pulmonary vein mechanical stretching exacerbated PH-LHD possibly through the SAC/MAPKs pathway and upregulating expression of IL-6 and TNF-α.

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“…Both laminar and disturbed flows activate the same initial mechanosignaling pathway involving Piezo1-and G q /G 11 -mediated signaling [2]. Accordingly, Piezo1 channel activator Yoda1 induces NO-mediated relaxation of murine intrapulmonary arteries [101].…”

Section: Mechanosensitive Channels In the Endotheliummentioning

confidence: 99%

It takes more than two to tango: mechanosignaling of the endothelial surface

Fels

Kusche-Vihrog

2020

Pflugers Arch - Eur J Physiol

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The endothelial surface is a highly flexible signaling hub which is able to sense the hemodynamic forces of the streaming blood. The subsequent mechanosignaling is basically mediated by specific structures, like the endothelial glycocalyx building the top surface layer of endothelial cells as well as mechanosensitive ion channels within the endothelial plasma membrane. The mechanical properties of the endothelial cell surface are characterized by the dynamics of cytoskeletal proteins and play a key role in the process of signal transmission from the outside (lumen of the blood vessel) to the interior of the cell. Thus, the cell mechanics directly interact with the function of mechanosensitive structures and ion channels. To precisely maintain the vascular tone, a coordinated functional interdependency between endothelial cells and vascular smooth muscle cells is necessary. This is given by the fact that mechanosensitive ion channels are expressed in both cell types and that signals are transmitted via autocrine/paracrine mechanisms from layer to layer. Thus, the outer layer of the endothelial cells can be seen as important functional mechanosensitive and reactive cellular compartment. This review aims to describe the known mechanosensitive structures of the vessel building a bridge between the important role of physiological mechanosignaling and the proper vascular function. Since mutations and dysfunction of mechanosensitive proteins are linked to vascular pathologies such as hypertension, they play a potent role in the field of channelopathies and mechanomedicine.

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Stretch-activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries

Cited by 49 publications

References 36 publications

Force Sensing by Piezo Channels in Cardiovascular Health and Disease

Force Sensing by Piezo Channels in Cardiovascular Health and Disease

Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α

It takes more than two to tango: mechanosignaling of the endothelial surface

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