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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Phenotypic switching prevention and proliferation/migration inhibition of vascular smooth muscle cells by the ruthenium nitrosyl complex trans-[Ru(NO)Cl(cyclam](PF6)(2)

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de Oliveira, Mariana G. ; Doro, Fabio G. ; Tfouni, Elia ; Krieger, Marta H.
Total Authors: 4
Document type: Journal article
Source: Journal of Pharmacy and Pharmacology; v. 69, n. 9, p. 1155-1165, SEP 2017.
Web of Science Citations: 5

ObjectivesVascular smooth muscle cell (VSMC) migration and proliferation at sites of vascular injury are both critical steps in the development of intimal hyperplasia (IH). Local delivery of nitric oxide (NO) largely prevents these events. Among the NO donors, tetraazamacrocyclic nitrosyl complexes, such as trans-{[}Ru(NO)Cl(cyclam)](PF6)(2) (cyclamNO), gained attention for their features, which include the possibility of being embedded in solid matrices, and ability to participate in a nitrite/NO catalytic conversion cycle. MethodsMethods used to evaluate cyclamNO activity: safety margin by NR and MTT; cell proliferation by 3H-thymidine incorporation and proliferating cell nuclear antigen (PCNA) expression; antimigratory properties by transwell and wound healing; prevention of cell phenotypic switching under platelet-derived growth factor type BB (PDGF-BB) stimuli by analysis of alpha smooth muscle actin (-SMA) expression. Key findingsCell proliferation and migration induced by PDGF-BB were significantly inhibited by cyclamNO. The similar to 60% reduction on expression of contractile protein -SMA induced by PDGF-BB revealed VSMC phenotypic switching which is significantly prevented by cyclamNO. Compared to the NO donor sodium nitroprusside, cyclamNO showed to be significantly less cytotoxic. ConclusionsWith great potential to maintain VSMC functionality and prevent IH-associated events, cyclamNO might be a promissory drug for several applications in cardiovascular medicine, as in stents. (AU)

FAPESP's process: 11/07376-0 - In vitro evaluation of the vascular reestenosis prevention and reendotheliazation with new nitric oxide eluinting materials
Grantee:Marta Helena Krieger
Support Opportunities: Regular Research Grants
FAPESP's process: 06/53266-4 - Chemistry, photochemistry and biological applications of ruthenium complexes with nitric oxide and related species. From solution to materials
Grantee:Elia Tfouni
Support Opportunities: Research Projects - Thematic Grants