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Heparin Responses in Vascular Smooth Muscle Cells Involve cGMP‐Dependent Protein Kinase (PKG)
Author(s) -
Gilotti Albert C.,
Nimlamool Wutigri,
Pugh Raymond,
Slee Joshua B.,
Barthol Trista C.,
Miller Elizabeth A.,
LoweKrentz Linda J.
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24677
Subject(s) - heparin , vascular smooth muscle , protein kinase a , cgmp dependent protein kinase , microbiology and biotechnology , mapk/erk pathway , biology , signal transduction , chemistry , kinase , mitogen activated protein kinase kinase , endocrinology , biochemistry , smooth muscle
Published data provide strong evidence that heparin treatment of proliferating vascular smooth muscle cells results in decreased signaling through the ERK pathway and decreases in cell proliferation. In addition, these changes have been shown to be mimicked by antibodies that block heparin binding to the cell surface. Here, we provide evidence that the activity of protein kinase G is required for these heparin effects. Specifically, a chemical inhibitor of protein kinase G, Rp‐8‐pCPT‐cGMS, eliminates heparin and anti‐heparin receptor antibody effects on bromodeoxyuridine incorporation into growth factor‐stimulated cells. In addition, protein kinase G inhibitors decrease heparin effects on ERK activity, phosphorylation of the transcription factor Elk‐1, and heparin‐induced MKP‐1 synthesis. Although transient, the levels of cGMP increase in heparin treated cells. Finally, knock down of protein kinase G also significantly decreases heparin effects in growth factor‐activated vascular smooth muscle cells. Together, these data indicate that heparin effects on vascular smooth muscle cell proliferation depend, at least in part, on signaling through protein kinase G. J. Cell. Physiol. 229: 2142–2152, 2014. © 2014 Wiley Periodicals, Inc.