Anti-growth properties of BAY 41-2272 in vascular smooth muscle cells

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Natalia N. Mendelev (Creator)

David A. Tulis (Creator)

Verietta S. Williams (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

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 (sGC) 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 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 (VASP) phosphorylation. BAY significantly elevated cyclin E expression decreased expression of the regulatory cyclin-dependent kinases (Cdk)-2 and -6 increased expression of cell cycle inhibitory p21WAF1/Cip1 and p27Kip1 and reduced expression of phosphorylated focal adhesion kinase (FAK). These comprehensive findings provide first evidence for the anti-growth 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. Originally published Journal of Cardiovascular Pharmacology Vol. 53 No. 2 Feb 2009

Additional Information

Publication

Other

Journal of Cardiovascular Pharmacology. 53:2(February 2009) p. 121-131.

Language: English

Date: 2011

Keywords

BAY 41-2272, cyclic GMP, cyclins, Protein kinases, vascular smooth muscle

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