CTP synthase 1, a smooth muscle-sensitive therapeutic target for effective vascular repair

Arteriosclerosis, Thrombosis, and Vascular Biology
Rui TangShi-You Chen

Abstract

Vascular remodeling as a result of smooth muscle cell (SMC) proliferation and neointima formation is a major medical challenge in cardiovascular intervention. However, antineointima drugs often indistinguishably block re-endothelialization, an essential step toward successful vascular repair, because of their nonspecific effect on endothelial cells (ECs). The objective of this study is to identify a therapeutic target that differentially regulates SMC and EC proliferation. Using both rat balloon injury and mouse wire injury models, we identified CTP synthase 1 (CTPS1) as one of the potential targets that may be used for developing therapeutics for treating neointima-related disorders. CTPS1 was induced in proliferative SMCs in vitro and neointima SMCs in vivo. Blockade of CTPS1 expression by small hairpin RNA or activity by cyclopentenyl cytosine suppressed SMC proliferation and neointima formation. Surprisingly, cyclopentenyl cytosine had much less effect on EC proliferation. Of importance, blockade of CTPS1 in vivo sustained the re-endothelialization as a result of induction of CTP synthesis salvage pathway enzymes nucleoside-diphosphate kinase A and B in ECs. Diphosphate kinase B seemed to preserve EC proliferation via use o...Continue Reading

References

Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J FingerleM A Reidy
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·P M PolitiJ M Hamilton
Jun 20, 1995·Proceedings of the National Academy of Sciences of the United States of America·R MorishitaV J Dzau
Aug 15, 1993·European Journal of Biochemistry·A A van den BergA H van Gennip
Feb 1, 1997·The American Journal of Physiology·K MurakamiK Takatsuki
Aug 11, 1997·The Journal of Cell Biology·D W DawsonN P Bouck
Nov 5, 1997·Progress in Cardiovascular Diseases·C Bauters, J M Isner
Jul 21, 1998·The Journal of Biological Chemistry·D B OstranderG M Carman
Apr 17, 1999·The Journal of Biological Chemistry·M DhanabalV P Sukhatme
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·A HoferL Thelander
Aug 17, 2001·Current Opinion in Lipidology·S KinlayP Ganz
Sep 14, 2004·Current Opinion in Lipidology·Philippe G Frank, Michael P Lisanti
Oct 27, 2005·European Heart Journal·Sjoerd H HofmaPatrick W Serruys
Apr 28, 2006·Antimicrobial Agents and Chemotherapy·M C Georges-CourbotV Deubel
Aug 19, 2007·Current Cancer Drug Targets·K J M SchimmelH J Guchelaar
Apr 22, 2009·Molecular and Cellular Biochemistry·Edith Horn PostelKrista M D La Perle

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Citations

Jan 20, 2011·Annals of General Psychiatry·Laura ReddenMario Saltarelli
Sep 13, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Kimie Tanaka, Masataka Sata
Sep 19, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Valerie Z Wall, Karin E Bornfeldt
Oct 21, 2015·Cellular and Molecular Life Sciences : CMLS·Keyvan Karimi GalougahiZiad A Ali
Dec 12, 2013·Expert Review of Cardiovascular Therapy·Rui Tang, Shi-You Chen

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