Skip Navigation LinksHome > February 2009 - Volume 53 - Issue 2 > Antigrowth Properties of BAY 41-2272 in Vascular Smooth Musc...
Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0b013e31819715c4
Original Article

Antigrowth Properties of BAY 41-2272 in Vascular Smooth Muscle Cells

Mendelev, Natalia N BS, MS*; Williams, Verietta S BS, MA*; Tulis, David A BS, MS, PhD, FAHA*†‡

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Abstract

Vascular smooth muscle (VSM) growth is integral in the pathophysiology of blood vessel diseases, and identifying approaches that have capacity to regulate VSM growth is critically essential. Cyclic nucleotide signaling has been generally considered protective in cardiac and vascular tissues and has been the target of numerous basic science and clinical studies. In this project, the influence of BAY 41-2272 (BAY), a recently described soluble guanylate cyclase stimulator and inducer of cyclic guanosine monophosphate (cGMP) synthesis, on VSM cell growth was analyzed. In rat A7R5 VSM cells, BAY significantly reduced proliferation in a dose- and time-dependent fashion. BAY activated cGMP and cyclic adenosine monophosphate (cAMP) signaling evidenced through elevated cGMP and cAMP content, increased expression of cyclic nucleotide-dependent protein kinases, and differential vasodilator-stimulated phosphoprotein phosphorylation. BAY significantly elevated cyclin E expression, decreased expression of the regulatory cyclin-dependent kinases -2 and -6, increased expression of cell cycle inhibitory p21WAF1/Cip1 and p27Kip1, and reduced expression of phosphorylated focal adhesion kinase. These comprehensive findings provide first evidence for the antigrowth cell cycle-regulatory properties of the neoteric agent, BAY 41-2272, in VSM and lend support for its continued study in the clinical and basic cardiovascular sciences.

© 2009 Lippincott Williams & Wilkins, Inc.

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