(HealthDay News) – A novel strategy using cyclopentenyl cytosine or other CTP synthase (CTPS) 1 inhibitors to coat stents can selectively block proliferation of smooth muscle cells (SMCs) without disturbing vascular repair and may potentially reduce the risk of blood clotting, according to research published online Sept. 5 in Arteriosclerosis, Thrombosis, and Vascular Biology.
Rui Tang, of the University of Georgia in Athens, and colleagues used rat balloon-injury and mouse wire-injury models to identify potential therapeutic targets for neointima-related disorders.
The researchers found that blockade of CTPS1 expression by small hairpin RNA or activity by cyclopentenyl cytosine suppressed proliferation of SMCs with much less effect on proliferation of endothelial cells (ECs). Blockade of CTPS1 in vivo induced enzymes of the CTP synthesis salvage pathway (nucleoside diphosphate kinase A and B) in ECs and promoted vascular repair. Blockade of both CTPS1 and diphosphate kinase B suppressed proliferation of ECs in vitro and re-endothelialization in vivo.
“Our study identified CTPS1 as a novel target for developing anti-neointima drugs that are SMC-sensitive but have little side-effect on re-endothelialization during vascular repair,” the authors write.