Journal Article

Differential vasodilation of human placental and myometrial arteries related to myofilament Ca2+-desensitization and the expression of Hsp20 but not MYPT1

A.C. Dordea, M. Sweeney, J. Taggart, J. Lartey, H. Wessel, S.C. Robson and M.J. Taggart

in MHR: Basic science of reproductive medicine

Published on behalf of European Society of Human Reproduction and Embryology

Volume 19, issue 11, pages 727-736
Published in print November 2013 | ISSN: 1360-9947
Published online June 2013 | e-ISSN: 1460-2407 | DOI: https://dx.doi.org/10.1093/molehr/gat045
Differential vasodilation of human placental and myometrial arteries related to myofilament Ca2+-desensitization and the expression of Hsp20 but not MYPT1

More Like This

Show all results sharing this subject:

  • Reproductive Medicine

GO

Show Summary Details

Preview

Endothelial-dependent regulation of vascular tone occurs in part via protein kinase G1α-mediated changes in smooth muscle myofilament sensitivity to Ca2+. Tissue-specific differences in PKG-dependent relaxation have been attributed to altered expression of myofilament-associated proteins that are substrates for PKG binding. These include the alternative splicing of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase to yield leucine zipper positive (LZ+) and negative (LZ) isovariants, with the former being required for PKG-mediated relaxation, and/or altered expressions of telokin, vasodilator-stimulated phosphoprotein (VASP) or heat shock protein Hsp20. During human pregnancy the uterine and placental circulations remain distinct entities and, as such, their mechanisms of vascular tone regulation may differ. Indeed, the sensitivity of myometrial arteries to endothelial-dependent agonists has been suggested to be greater than that of placental arteries. We tested the hypothesis that this was related to tissue-specific changes in PKG-mediated myofilament Ca2+-desensitization and/or the expressions of PKG-interacting myofilament-associated proteins. Permeabilized human placental and myometrial arteries were constricted with maximal activating Ca2+ (pCa 4.5), or sub-maximal Ca2+ (pCa 6.7) and the thrombane mimetic U46619, and exposed to 8-Br-cGMP. In each case, relaxation was significantly greater in myometrial arteries (e.g. relaxation in pCa 4.5 to 8-Br-cGMP was 49 ± 9.7%, n = 7) than placental arteries (relaxation of 23 ± 6.6%, n = 6, P < 0.05). MYPT1 protein levels, or MYPT1 LZ+/LZ mRNA ratios, were similar for both artery types. Of other proteins examined, only Hsp20 expression was significantly elevated in myometrial arteries than placental arteries. These results demonstrate that the reduced human placental artery relaxation to PKG stimulation lies partly at the level of myofilament (de)activation and may be related to a lower expression of Hsp20 than in myometrial arteries.

Keywords: human placental arteries; human myometrial arteries; PKG; Hsp20

Journal Article.  4890 words.  Illustrated.

Subjects: Reproductive Medicine

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content. subscribe or purchase to access all content.