Abstract
Stimulation of vascular smooth muscle (VSM) α1-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. Δ6 (D6d) and Δ5 (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 PGF2α secretion. Together these findings suggest that PUFA biosynthesis in VSM cells is involved in calcium release associated with vasoconstriction.
References
Jul 1, 1991·Lipids·S ShimizuH Yamada
Sep 1, 1990·Pflügers Archiv : European journal of physiology·B HimpensA P Somlyo
Nov 15, 1990·Biochemical and Biophysical Research Communications·T Kitazawa, A P Somlyo
Apr 1, 1990·Lipids·M C GarciaM D Rosenthal
Jul 1, 1988·Lipids·A C Voss, H Sprecher
Apr 1, 1997·The Journal of Physiology·P GaillyA P Somlyo
Sep 2, 1999·Prostaglandins, Leukotrienes, and Essential Fatty Acids·H Sprecher, Q Chen
Dec 10, 1999·Cell·A P Bird, A P Wolffe
Apr 11, 2001·Pflügers Archiv : European journal of physiology·S ArakiT Nakano
Jul 10, 2003·Lipids·Shawn D HarmonArthur A Spector
Sep 25, 2003·Physiological Reviews·Andrew P Somlyo, Avril V Somlyo
Oct 2, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·Erika ShimomuraKatsuaki Ito
Mar 28, 2006·Progress in Lipid Research·Andreas JakobssonAnders Jacobsson
Dec 21, 2007·BMC Molecular Biology·Stefan CikosJuraj Koppel
Jun 3, 2009·Cell Calcium·Paul H RatzSuzanne E Barbour
Apr 18, 2012·PloS One·Christopher J KelsallGraham C Burdge
Jan 15, 2014·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Charlene M SibbonsGraham C Burdge