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Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells

Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells
Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells
Stimulation of vascular smooth muscle (VSM) ?1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. ?6 (D6d) and ?5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2? secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction.
polyunsaturated fatty acids, vascular smooth muscle cells, calcium
31-39
Irvine, Nicola A.
411ef006-e98e-4d92-8faa-6805df87b01d
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Fielding, Barbara
26abb9ff-58bd-468e-bb37-10d1e27c5c70
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Irvine, Nicola A.
411ef006-e98e-4d92-8faa-6805df87b01d
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Fielding, Barbara
26abb9ff-58bd-468e-bb37-10d1e27c5c70
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Hanson, Mark A.
1952fad1-abc7-4284-a0bc-a7eb31f70a3f
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159

Irvine, Nicola A., Lillycrop, Karen A., Fielding, Barbara, Torrens, Christopher, Hanson, Mark A. and Burdge, Graham C. (2015) Polyunsaturated fatty acid biosynthesis is involved in phenylephrine-mediated calcium release in vascular smooth muscle cells. Prostaglandins, Leukotrienes and Essential Fatty Acids, 101, 31-39. (doi:10.1016/j.plefa.2015.08.001). (PMID:26324193)

Record type: Article

Abstract

Stimulation of vascular smooth muscle (VSM) ?1-adrenoceptors induces myosin phosphorylation and vasoconstriction via mobilisation of intracellular calcium and production of specific eicosanoids. Polyunsaturated fatty acid (PUFA) biosynthesis in VSM cells is involved, although the precise mechanism is not known. To address this, we characterised PUFA biosynthesis in VSM cells and determined its role in intracellular calcium release and eicosanoid production. Murine VSM cells converted 18:2n-6 to longer chain PUFA including 22:5n-6. ?6 (D6d) and ?5 (D5d) desaturase, and elongase (Elovl) 5 were expressed. Elovl2 was not detected in human, mouse or rat VSM cells, or in rat or mouse aortae, but tit was not associated with hypermethylation of its promoter. D6d or D5d inhibition reduced 18:3n-6 and 20:4n-6 synthesis, respectively, and induced concentration-related decrease in phenylephrine-mediated calcium release, and in PGE2 and PGF2? secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction.

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Accepted/In Press date: 11 August 2015
e-pub ahead of print date: 20 August 2015
Published date: October 2015
Keywords: polyunsaturated fatty acids, vascular smooth muscle cells, calcium
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 383070
URI: http://eprints.soton.ac.uk/id/eprint/383070
DOI: doi:10.1016/j.plefa.2015.08.001
PURE UUID: 64af9c14-58a9-4f1e-9795-57087837561d
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Mark A. Hanson: ORCID iD orcid.org/0000-0002-6907-613X
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967

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Date deposited: 21 Oct 2015 13:50
Last modified: 15 Mar 2024 03:07

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Contributors

Author: Nicola A. Irvine
Author: Karen A. Lillycrop ORCID iD
Author: Barbara Fielding
Author: Christopher Torrens
Author: Mark A. Hanson ORCID iD
Author: Graham C. Burdge ORCID iD

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