Premium
Piezo1 Regulation of Lung Endothelial Barrier Function in Left Heart Failure
Author(s) -
Friedrich Emily,
Hong Zhigang,
Zhong Ming,
Rehman Jalees,
Komarova Yulia,
Malik Asrar B.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.750.19
Subject(s) - piezo1 , endothelium , pulmonary edema , vascular permeability , lung , barrier function , heart failure , microbiology and biotechnology , cardiology , medicine , mechanosensitive channels , chemistry , biology , ion channel , receptor
Pulmonary edema is a potentially life‐threatening condition in which interstitial and alveolar spaces fill with fluid. This can be the result of left heart failure and a rise in lung capillary pressure. Piezo1 is a mechanosensitive ion channel expressed in endothelium that is activated by changes in plasma membrane curvature due to high pressure. Here, we address the role of Piezo1 in sensing increased lung capillary pressure that leads to endothelial barrier disruption through disassembly of Vascular Endothelial (VE)‐cadherin (VE‐cad) adhesion at adherens junctions (AJ). We showed that pulmonary capillary pressure rise of 16 cmH 2 O elicited increased permeability to liquid and albumin in lungs of Piezo1 +/+ mice and these responses were prevented in mice deleted of Piezo1 gene in endothelial cells ( Piezo1 iΔEC ). Piezo1 iΔEC mice demonstrated no significant change in lung vascular albumin permeability at 24h after aorta constriction, which causes capillary pressure and left heart failure, in contrast to Piezo1 +/+ mice, which demonstrated 4‐fold increase in permeability. Consistent with increased lung capillary permeability, activation of Piezo1‐mediated signaling increased VE‐cadherin phosphorylation at both Y685 and Y731 that coincided with VE‐cad internalization and AJ disassembly. Thus, Piezo1‐activated signaling in endothelial cells causes endothelial barrier disruption. These results uncover endothelial cell expressed Piezo1 as a new drug target for treatment pulmonary edema associated with left heart failure. Support or Funding Information This work was supported by National Institutes of Health Grants T32 grant and HL45638 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .