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Inhibition of Vascular Smooth Muscle Growth by the Soluble Guanylyl Cyclase Activator BAY 60–2770
Author(s) -
Martin Danielle Nicole,
Adderley Shaquria P,
Joshi Chintamani N,
Durante William,
Tulis David A
Publication year - 2013
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.27.1_supplement.1139.3
Subject(s) - bay , soluble guanylyl cyclase , activator (genetics) , vascular smooth muscle , cell growth , chemistry , microbiology and biotechnology , guanylate cyclase , cell , smooth muscle , endocrinology , biology , biochemistry , receptor , civil engineering , engineering
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are key components of pathologic vessel growth and efforts aimed at their reduction are clinically essential. Cyclic nucleotide signaling has long been studied for its growth‐mitigating properties, and in the current study we hypothesized that the novel soluble guanylyl cyclase activator BAY 60–2770 (BAY) inhibits proliferation and migration of rat primary VSMCs through PKA and PKG. BAY significantly reduced cell numbers in concentration‐dependent fashion after 72 h (0.1–10 μM) and S‐phase cell numbers (~40%) after 16 h with no effects on cell viability. Interestingly, BAY caused nominal reduction (~20%) in cell migration after 16 h. Mechanistically, BAY significantly induced cGMP in concentration‐and time‐dependent fashion without apparent effects on cAMP. In‐Cell Western analysis showed that BAY significantly increased phosphorylation of vasodilator‐stimulated phosphoprotein (VASP) at Ser157 and Ser239, respective indicators of PKA and PKG signaling. Lastly, BAY doubled PKG activity without observable effects on PKA activity. These data suggest that BAY has capacity to inhibit VSMC proliferation through cGMP/PKG/VASP signaling. This work was supported by NHLBI grants HL59976 and HL81720 and by an ECU Undergraduate Research and Creative Activity Award.