Myeloperoxidase upregulates endothelin receptor type B expression
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Myeloperoxidase upregulates endothelin receptor type B expression. / Lau, Denise; Szöcs, Katalin; Klinke, Anna; Rudolph, Tanja; Rudolph, Volker; Streichert, Thomas; Blankenberg, Stefan; Baldus, Stephan.
In: J MOL CELL CARDIOL, Vol. 69, 01.04.2014, p. 76-82.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Myeloperoxidase upregulates endothelin receptor type B expression
AU - Lau, Denise
AU - Szöcs, Katalin
AU - Klinke, Anna
AU - Rudolph, Tanja
AU - Rudolph, Volker
AU - Streichert, Thomas
AU - Blankenberg, Stefan
AU - Baldus, Stephan
N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - Neutrophil recruitment and activation are principal events in inflammation. Upon activation neutrophils release myeloperoxidase (MPO), a heme enzyme, which binds to and transcytoses endothelial cells. Whereas the significance of the subendothelial deposition of MPO has evolved as a critical prerequisite for the enzyme's suppression of nitric oxide (NO⋅) bioavailability, the functional consequences of MPO binding to and interaction with endothelial and smooth muscle cells remain poorly understood. Cultured human endothelial cells (HUVECs) were exposed to MPO. Gene expression of the endothelin receptor type B (ETRB), which is critically involved not only in endothelin-1 clearance, but also in endothelin-mediated vasoconstriction, was significantly increased. Real time PCR, Western blotting and immunofluorescence confirmed up-regulation of ETRB in MPO-treated endothelial cells. Inhibition of MPO's enzymatic activity blunted the increase in ETRB protein expression. Treatment of the cells with the MAP kinase inhibitors PD98059 or SB203580 indicates that MPO activates ETRB expression via MAP kinase pathways. On human smooth muscle cells (HAoSMCs), which not only express the endothelin receptor type B (ETRB) but also express the endothelin receptor type A (ETRA), MPO also stimulated ETRB expression as opposed to ETRA expression, which remained unchanged. Functional ex vivo organ bath chamber studies with MPO-incubated rat femoral artery sections revealed increased ETRB agonist dependent constriction. Binding of MPO to endothelial and vascular smooth muscle cells increases expression of the endothelin receptor type B (ETRB) via classical MAP kinase pathways. This suggests that MPO not only affects vasomotion by reducing the bioavailability of vasodilating molecules but also by increasing responsiveness to vasoconstrictors, further advocating for MPO as a central, leukocyte-derived regulator of vascular tone.
AB - Neutrophil recruitment and activation are principal events in inflammation. Upon activation neutrophils release myeloperoxidase (MPO), a heme enzyme, which binds to and transcytoses endothelial cells. Whereas the significance of the subendothelial deposition of MPO has evolved as a critical prerequisite for the enzyme's suppression of nitric oxide (NO⋅) bioavailability, the functional consequences of MPO binding to and interaction with endothelial and smooth muscle cells remain poorly understood. Cultured human endothelial cells (HUVECs) were exposed to MPO. Gene expression of the endothelin receptor type B (ETRB), which is critically involved not only in endothelin-1 clearance, but also in endothelin-mediated vasoconstriction, was significantly increased. Real time PCR, Western blotting and immunofluorescence confirmed up-regulation of ETRB in MPO-treated endothelial cells. Inhibition of MPO's enzymatic activity blunted the increase in ETRB protein expression. Treatment of the cells with the MAP kinase inhibitors PD98059 or SB203580 indicates that MPO activates ETRB expression via MAP kinase pathways. On human smooth muscle cells (HAoSMCs), which not only express the endothelin receptor type B (ETRB) but also express the endothelin receptor type A (ETRA), MPO also stimulated ETRB expression as opposed to ETRA expression, which remained unchanged. Functional ex vivo organ bath chamber studies with MPO-incubated rat femoral artery sections revealed increased ETRB agonist dependent constriction. Binding of MPO to endothelial and vascular smooth muscle cells increases expression of the endothelin receptor type B (ETRB) via classical MAP kinase pathways. This suggests that MPO not only affects vasomotion by reducing the bioavailability of vasodilating molecules but also by increasing responsiveness to vasoconstrictors, further advocating for MPO as a central, leukocyte-derived regulator of vascular tone.
U2 - 10.1016/j.yjmcc.2013.12.007
DO - 10.1016/j.yjmcc.2013.12.007
M3 - SCORING: Journal article
C2 - 24417960
VL - 69
SP - 76
EP - 82
JO - J MOL CELL CARDIOL
JF - J MOL CELL CARDIOL
SN - 0022-2828
ER -