LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction

Péter Tibor Dancs, Éva Ruisanchez, Andrea Balogh, Cecília Rita Panta, Zsuzsanna Miklós, Rolf M. Nüsing, Junken Aoki, Jerold Chun, Stefan Offermanns, Gabor Tigyi, Zoltán Benyó

Research output: Contribution to journalArticle

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Abstract

Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6. In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and theLPA1-3 agonistVPC31143 induced dosedependent vasoconstriction. VPC31143-induced AA contraction was sensitive to pertussis toxin (PTX), the LPA1&3 antagonist Ki16425, and genetic deletion of LPA1 but not that of LPA2 or inhibition of LPA3, by diacylglycerol pyrophosphate. Surprisingly, vasoconstriction was also diminished in vessels lacking cyclooxygenase-1 [COX1 knockout (KO)] or the thromboxaneprostanoid (TP) receptor (TPKO).VPC31143 increased thromboxaneA2(TXA2) release from TA of wild-type, TP-KO, and LPA2-KO mice but not from LPA1-KO or COX1-KO mice, and PTX blocked this effect. Our findings indicate that LPA causes vasoconstriction in VSMCs, mediated by LPA1-, Gi-, and COX1-dependent autocrine/paracrine TXA2 release and consequent TP activation. We propose that this new-found interaction between the LPA/LPA1 and TXA2/TP pathways plays significant roles in vasoregulation, hemostasis, thrombosis, and vascular remodeling.

Original languageEnglish (US)
Pages (from-to)1547-1555
Number of pages9
JournalFASEB Journal
Volume31
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Lysophosphatidic Acid Receptors
Thromboxane A2
Muscle Contraction
Vascular Smooth Muscle
Muscle
Vasoconstriction
Smooth Muscle Myocytes
Abdominal Aorta
Pertussis Toxin
Thoracic Aorta
Knockout Mice
Endothelium-Dependent Relaxing Factors
Cyclooxygenase 1
Hemostasis
Endothelium
Thrombosis
Genes
Chemical activation
Cells
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Dancs, P. T., Ruisanchez, É., Balogh, A., Panta, C. R., Miklós, Z., Nüsing, R. M., ... Benyó, Z. (2017). LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. FASEB Journal, 31(4), 1547-1555. https://doi.org/10.1096/fj.201600735R

LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. / Dancs, Péter Tibor; Ruisanchez, Éva; Balogh, Andrea; Panta, Cecília Rita; Miklós, Zsuzsanna; Nüsing, Rolf M.; Aoki, Junken; Chun, Jerold; Offermanns, Stefan; Tigyi, Gabor; Benyó, Zoltán.

In: FASEB Journal, Vol. 31, No. 4, 01.04.2017, p. 1547-1555.

Research output: Contribution to journalArticle

Dancs, PT, Ruisanchez, É, Balogh, A, Panta, CR, Miklós, Z, Nüsing, RM, Aoki, J, Chun, J, Offermanns, S, Tigyi, G & Benyó, Z 2017, 'LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction', FASEB Journal, vol. 31, no. 4, pp. 1547-1555. https://doi.org/10.1096/fj.201600735R
Dancs, Péter Tibor ; Ruisanchez, Éva ; Balogh, Andrea ; Panta, Cecília Rita ; Miklós, Zsuzsanna ; Nüsing, Rolf M. ; Aoki, Junken ; Chun, Jerold ; Offermanns, Stefan ; Tigyi, Gabor ; Benyó, Zoltán. / LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. In: FASEB Journal. 2017 ; Vol. 31, No. 4. pp. 1547-1555.
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abstract = "Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6. In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and theLPA1-3 agonistVPC31143 induced dosedependent vasoconstriction. VPC31143-induced AA contraction was sensitive to pertussis toxin (PTX), the LPA1&3 antagonist Ki16425, and genetic deletion of LPA1 but not that of LPA2 or inhibition of LPA3, by diacylglycerol pyrophosphate. Surprisingly, vasoconstriction was also diminished in vessels lacking cyclooxygenase-1 [COX1 knockout (KO)] or the thromboxaneprostanoid (TP) receptor (TPKO).VPC31143 increased thromboxaneA2(TXA2) release from TA of wild-type, TP-KO, and LPA2-KO mice but not from LPA1-KO or COX1-KO mice, and PTX blocked this effect. Our findings indicate that LPA causes vasoconstriction in VSMCs, mediated by LPA1-, Gi-, and COX1-dependent autocrine/paracrine TXA2 release and consequent TP activation. We propose that this new-found interaction between the LPA/LPA1 and TXA2/TP pathways plays significant roles in vasoregulation, hemostasis, thrombosis, and vascular remodeling.",
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AU - Dancs, Péter Tibor

AU - Ruisanchez, Éva

AU - Balogh, Andrea

AU - Panta, Cecília Rita

AU - Miklós, Zsuzsanna

AU - Nüsing, Rolf M.

AU - Aoki, Junken

AU - Chun, Jerold

AU - Offermanns, Stefan

AU - Tigyi, Gabor

AU - Benyó, Zoltán

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AB - Lysophosphatidic acid (LPA) has been recognized recently as an endothelium-dependent vasodilator, but several lines of evidence indicate that it may also stimulate vascular smooth muscle cells (VSMCs), thereby contributing to vasoregulation and remodeling. In the present study, mRNA expression of all 6 LPA receptor genes was detected in murine aortic VSMCs, with the highest levels of LPA1, LPA2, LPA4, and LPA6. In endothelium-denuded thoracic aorta (TA) and abdominal aorta (AA) segments, 1-oleoyl-LPA and theLPA1-3 agonistVPC31143 induced dosedependent vasoconstriction. VPC31143-induced AA contraction was sensitive to pertussis toxin (PTX), the LPA1&3 antagonist Ki16425, and genetic deletion of LPA1 but not that of LPA2 or inhibition of LPA3, by diacylglycerol pyrophosphate. Surprisingly, vasoconstriction was also diminished in vessels lacking cyclooxygenase-1 [COX1 knockout (KO)] or the thromboxaneprostanoid (TP) receptor (TPKO).VPC31143 increased thromboxaneA2(TXA2) release from TA of wild-type, TP-KO, and LPA2-KO mice but not from LPA1-KO or COX1-KO mice, and PTX blocked this effect. Our findings indicate that LPA causes vasoconstriction in VSMCs, mediated by LPA1-, Gi-, and COX1-dependent autocrine/paracrine TXA2 release and consequent TP activation. We propose that this new-found interaction between the LPA/LPA1 and TXA2/TP pathways plays significant roles in vasoregulation, hemostasis, thrombosis, and vascular remodeling.

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