Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves

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Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves. / Witt, Wolfgang; Jannasch, Anett; Burkhard, Daniela; Christ, Torsten; Ravens, Ursula; Brunssen, Coy; Leuner, Anja; Morawietz, Henning; Matschke, Klaus; Waldow, Thomas.

in: CARDIOVASC RES, Jahrgang 93, Nr. 3, 01.03.2012, S. 490-7.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Witt, W, Jannasch, A, Burkhard, D, Christ, T, Ravens, U, Brunssen, C, Leuner, A, Morawietz, H, Matschke, K & Waldow, T 2012, 'Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves', CARDIOVASC RES, Jg. 93, Nr. 3, S. 490-7. https://doi.org/10.1093/cvr/cvs002

APA

Witt, W., Jannasch, A., Burkhard, D., Christ, T., Ravens, U., Brunssen, C., Leuner, A., Morawietz, H., Matschke, K., & Waldow, T. (2012). Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves. CARDIOVASC RES, 93(3), 490-7. https://doi.org/10.1093/cvr/cvs002

Vancouver

Bibtex

@article{4966b6ea856b4c49bc541fc83bad3683,
title = "Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves",
abstract = "AIMS: Sphingosine-1-phosphate (S1P) has emerged as a potent bioactive lipid with multiple functions in cardiovascular pathophysiology. Potential roles of S1P in heart valve diseases and expression of relevant receptors (S1P1, S1P2, or S1P3) in valve tissue and in valvular interstitial cells (VICs), the major cell population with essential functions in maintenance of valvular structure, are currently unknown.METHODS AND RESULTS: Exposure to S1P (62-2000 nM) of cultured VICs from porcine aortic valves on cell culture polystyrene resulted in contraction and nodule formation. The S1P-dependent contraction was completely inhibited by blockers of S1P2, RhoA, and RhoA-associated protein kinase (ROCK). Activated RhoA was clearly increased after S1P treatment, whereas activated Rac1 was only slightly reduced. In addition, exposure to S1P induced a transient increase in cytosolic Ca(2+). Application of channel blockers and other effectors of Ca(2+) homeostasis showed that the S1P effect is largely caused by Ca(2+) release from internal stores. However, resistance to blocking S1P2, different kinetics, as well as concentration dependence exclude a major role of Ca(2+) influx in S1P-induced nodule formation. In order to verify the effects in situ, contractions of valve tissue slices were measured. The S1P-induced isometric contraction of valve leaflets was of similar force amplitude as observed with adrenaline. The effect was fully reversed by blocking S1P2.CONCLUSION: The results suggest that S1P induces contraction of VICs from porcine aortic valves by signalling via S1P2, RhoA, and ROCK. In this way, S1P may contribute to regulation of tissue tension in aortic valves.",
keywords = "Animals, Aortic Valve/cytology, Calcium/metabolism, Cells, Cultured, Epinephrine/physiology, Gene Expression/physiology, Isometric Contraction/drug effects, Lysophospholipids/pharmacology, Receptors, Lysosphingolipid/genetics, Signal Transduction/drug effects, Sphingosine/analogs & derivatives, Stress, Mechanical, Sus scrofa, rac1 GTP-Binding Protein/metabolism, rhoA GTP-Binding Protein/metabolism",
author = "Wolfgang Witt and Anett Jannasch and Daniela Burkhard and Torsten Christ and Ursula Ravens and Coy Brunssen and Anja Leuner and Henning Morawietz and Klaus Matschke and Thomas Waldow",
year = "2012",
month = mar,
day = "1",
doi = "10.1093/cvr/cvs002",
language = "English",
volume = "93",
pages = "490--7",
journal = "CARDIOVASC RES",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Sphingosine-1-phosphate induces contraction of valvular interstitial cells from porcine aortic valves

AU - Witt, Wolfgang

AU - Jannasch, Anett

AU - Burkhard, Daniela

AU - Christ, Torsten

AU - Ravens, Ursula

AU - Brunssen, Coy

AU - Leuner, Anja

AU - Morawietz, Henning

AU - Matschke, Klaus

AU - Waldow, Thomas

PY - 2012/3/1

Y1 - 2012/3/1

N2 - AIMS: Sphingosine-1-phosphate (S1P) has emerged as a potent bioactive lipid with multiple functions in cardiovascular pathophysiology. Potential roles of S1P in heart valve diseases and expression of relevant receptors (S1P1, S1P2, or S1P3) in valve tissue and in valvular interstitial cells (VICs), the major cell population with essential functions in maintenance of valvular structure, are currently unknown.METHODS AND RESULTS: Exposure to S1P (62-2000 nM) of cultured VICs from porcine aortic valves on cell culture polystyrene resulted in contraction and nodule formation. The S1P-dependent contraction was completely inhibited by blockers of S1P2, RhoA, and RhoA-associated protein kinase (ROCK). Activated RhoA was clearly increased after S1P treatment, whereas activated Rac1 was only slightly reduced. In addition, exposure to S1P induced a transient increase in cytosolic Ca(2+). Application of channel blockers and other effectors of Ca(2+) homeostasis showed that the S1P effect is largely caused by Ca(2+) release from internal stores. However, resistance to blocking S1P2, different kinetics, as well as concentration dependence exclude a major role of Ca(2+) influx in S1P-induced nodule formation. In order to verify the effects in situ, contractions of valve tissue slices were measured. The S1P-induced isometric contraction of valve leaflets was of similar force amplitude as observed with adrenaline. The effect was fully reversed by blocking S1P2.CONCLUSION: The results suggest that S1P induces contraction of VICs from porcine aortic valves by signalling via S1P2, RhoA, and ROCK. In this way, S1P may contribute to regulation of tissue tension in aortic valves.

AB - AIMS: Sphingosine-1-phosphate (S1P) has emerged as a potent bioactive lipid with multiple functions in cardiovascular pathophysiology. Potential roles of S1P in heart valve diseases and expression of relevant receptors (S1P1, S1P2, or S1P3) in valve tissue and in valvular interstitial cells (VICs), the major cell population with essential functions in maintenance of valvular structure, are currently unknown.METHODS AND RESULTS: Exposure to S1P (62-2000 nM) of cultured VICs from porcine aortic valves on cell culture polystyrene resulted in contraction and nodule formation. The S1P-dependent contraction was completely inhibited by blockers of S1P2, RhoA, and RhoA-associated protein kinase (ROCK). Activated RhoA was clearly increased after S1P treatment, whereas activated Rac1 was only slightly reduced. In addition, exposure to S1P induced a transient increase in cytosolic Ca(2+). Application of channel blockers and other effectors of Ca(2+) homeostasis showed that the S1P effect is largely caused by Ca(2+) release from internal stores. However, resistance to blocking S1P2, different kinetics, as well as concentration dependence exclude a major role of Ca(2+) influx in S1P-induced nodule formation. In order to verify the effects in situ, contractions of valve tissue slices were measured. The S1P-induced isometric contraction of valve leaflets was of similar force amplitude as observed with adrenaline. The effect was fully reversed by blocking S1P2.CONCLUSION: The results suggest that S1P induces contraction of VICs from porcine aortic valves by signalling via S1P2, RhoA, and ROCK. In this way, S1P may contribute to regulation of tissue tension in aortic valves.

KW - Animals

KW - Aortic Valve/cytology

KW - Calcium/metabolism

KW - Cells, Cultured

KW - Epinephrine/physiology

KW - Gene Expression/physiology

KW - Isometric Contraction/drug effects

KW - Lysophospholipids/pharmacology

KW - Receptors, Lysosphingolipid/genetics

KW - Signal Transduction/drug effects

KW - Sphingosine/analogs & derivatives

KW - Stress, Mechanical

KW - Sus scrofa

KW - rac1 GTP-Binding Protein/metabolism

KW - rhoA GTP-Binding Protein/metabolism

U2 - 10.1093/cvr/cvs002

DO - 10.1093/cvr/cvs002

M3 - SCORING: Journal article

C2 - 22232739

VL - 93

SP - 490

EP - 497

JO - CARDIOVASC RES

JF - CARDIOVASC RES

SN - 0008-6363

IS - 3

ER -