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An essential role of calcium‐independent phospholipase A2 beta in up‐regulation of RGS2 mRNA by Angiotensin II in cultured vascular smooth muscle cells
Author(s) -
Xie Zhongwen,
Su Wen,
Turk John,
Gong Ming C,
Guo Zhenheng
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1031-b
Up‐regulation of RGS2 mRNA by angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) is considered as a potentially important negative feedback mechanism in maintaining blood pressure homeostasis. However, the mechanism underlying Ang II‐induced RGS2 mRNA up‐regulation is largely unknown. We hypothesize that calcium‐independent phospholipase A 2 beta (iPLA 2 beta) plays a pivotal role in Ang II‐induced RGS2 mRNA up‐regulation in VSMC. RGS2 mRNA was measured by real‐time PCR in rat or mouse VSMC. Our results demonstrate that selective inhibition of iPLA 2 beta with inhibitor BEL, antisense oligonucleotides, or genetic deletion, abolished Ang II‐induced up‐regulation of RGS2 mRNA. Further, in iPLA 2 beta deficient VSMC, reconstitution of iPLA 2 beta protein by adenoviral vector dose‐ dependently restored the lost Ang II‐induced RGS2 up‐regulation. However, neither BEL nor iPLA 2 beta deletion affected Ang II‐induced vasodilator‐stimulated phosphoprotein (VASP) phosphorylation. In addition, in wild type‐, but not iPLA 2 beta deficient‐cells, Ang II significantly stimulated iPLA 2 beta enzymatic activity. Arachidonic acid and lysophosphotidylcholine, two major products of iPLA 2 , dose‐dependently induced RGS2 mRNA up‐regulation. Collectively, our results establish an essential role of iPLA 2 beta in Ang II‐induced RGS2 RNA up‐regulation in VSMC. (Supported by an AHA SDG to ZG and HL67284 and HL082791 to MCG.)