The Cyclic GMP Modulators YC-1 and Zaprinast Reduce Vessel Remodeling Through Antiproliferative and Proapoptotic Effects
Open Access
- 2 April 2009
- journal article
- research article
- Published by SAGE Publications in Journal of Cardiovascular Pharmacology and Therapeutics
- Vol. 14 (2), 116-124
- https://doi.org/10.1177/1074248409333266
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 200Keywords
This publication has 37 references indexed in Scilit:
- Novel Therapies for Cyclic GMP Control of Vascular Smooth Muscle GrowthClinical Journal of Sport Medicine, 2008
- Role of Smooth Muscle cGMP/cGKI Signaling in Murine Vascular RestenosisArteriosclerosis, Thrombosis, and Vascular Biology, 2008
- Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Cilostazol Inhibits Vascular Smooth Muscle Cell Growth by Downregulation of the Transcription Factor E2FHypertension, 2005
- Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cellsBlood, 2003
- YC-1-Mediated Vascular Protection through Inhibition of Smooth Muscle Cell Proliferation and Platelet FunctionBiochemical and Biophysical Research Communications, 2002
- Phosphodiesterase Type 5 Inhibition Enhances Vasorelaxation Caused by Nitroprusside in Guinea Pig Intact Heart and Isolated AortaJournal of Cardiovascular Pharmacology, 2000
- Suppression of arterial intimal hyperplasia by cilostamide, a cyclic nucleotide phosphodiesterase 3 inhibitor, in a rat balloon double‐injury modelBritish Journal of Pharmacology, 2000
- Effect of atrial natriuretic peptide and cyclic GMP phosphodiesterase inhibition on collagen synthesis by adult cardiac fibroblastsBritish Journal of Pharmacology, 1998
- In vivo Inhibition of Platelet Adhesion by a cGMP-Mediated Mechanism in Balloon Catheter Injured Rat Carotid ArteryPharmacology, 1996