The cyclic GMP modulators YC-1 and zaprinast reduce vessel remodeling through anti-proliferative and pro-apoptotic effects

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

William Durante (Creator)

Amit N. Keswani (Creator)

Kelly J. Peyton (Creator)

Andrew I. Schafer (Creator)

David A. Tulis (Creator)

Institution

East Carolina University (ECU )

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

Abstract: Guanosine-specific cyclic nucleotide signaling is suggested to serve protective actions in the vasculature; however the influence of selective pharmacologic modulation of cyclic guanosine monophosphate (GMP)-synthesizing soluble guanylate cyclase (sGC) or cyclic GMP-degrading phosphodiesterase (PDE) on vessel remodeling has not been thoroughly examined. In this study rat carotid artery balloon injury was performed and the growth-modulating effects of the sGC stimulator YC-1 or the cGMP-dependent PDE-V inhibitor zaprinast were examined. YC-1 or zaprinast elevated vessel cyclic GMP content reduced medial wall and neointimal cell proliferation stimulated medial and neointimal cellular apoptosis and markedly attenuated neointimal remodeling in comparable fashion. Interestingly sGC inhibition by ODQ failed to noticeably alter neointimal growth and concomitant zaprinast with YC-1 did not modify any parameter compared to individual treatments. These results provide novel in vivo evidence that YC-1 and zaprinast inhibit injury-induced vascular remodeling through anti-mitogenic and pro-apoptotic actions and may offer promising therapeutic approaches against vasoproliferative disorders. Originally published J Cardiovasc Pharmacol Ther Vol. 14 No. 2 June 2009

Additional Information

Publication

Other

Journal of Cardiovascular Pharmacology and Therapeutics. 14:2(June 2009) p. 116-124.

Language: English

Date: 2011

Keywords

Apoptosis, carotid artery balloon injury, Proliferation, YC-1, zaprinast

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