© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
YC-1 prevents sodium nitroprusside-mediated apoptosis in vascular smooth muscle cells
aPharmacological Institute, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Section 1, 100 Taipei, Taiwan
bSchool of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
cGraduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan
dYung-Shin Pharmaceutical Industry Co., Ltd., Taichung, Taiwan
* Corresponding author. Tel./fax: +886-2-2322-1742. cmteng{at}ha.mc.ntu.edu.tw
Objective: Nitric oxide signaling pathways are of central importance in both the maintenance of vascular homeostasis and the progression of vascular disease. Since smooth muscle cell apoptosis is associated with numerous vascular disorders, the authors investigated whether YC-1, a soluble guanylyl cyclase (sGC) activator, regulates apoptosis in vascular smooth muscle cells (VSMC). Methods and results: Sodium nitroprusside (SNP) (1 mM) induced cGMP (guanosine 3':5'-cyclic monophosphate)-independent apoptosis in rat vascular smooth muscle cells using MTT assay and TUNEL-reaction techniques. Furthermore, sodium nitroprusside induced apoptosis via Bcl-2 down-regulation, cytochrome c release reaction, and caspase-3 activation by Western blotting analysis and enzymatic assay methods. YC-1 abolished these apoptotic signaling cascades and prevented apoptosis through a cGMP-involved pathway, and phosphatidylinositol (PI) 3-kinase behaved a downstream event in this pathway. Conclusions: These results suggest that YC-1 inhibits sodium nitroprusside-induced vascular smooth muscle cells apoptosis via a cGMP- and phosphatidylinositol 3-kinase-involved inhibition on Bcl-2 down-regulation/cytochrome c release/caspase-3 activation cascades. The ability of YC-1 to prevent smooth muscle cell apoptosis may play an important role in blocking lesion formation at sites of vascular injury.
KEYWORDS YC-1; Vascular smooth muscle cells; Apoptosis; Nitric oxide
Time for primary review 20 days
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