cyclic-gmp and selenocystamine

The development of a nitric oxide (NO)-generating surface with long-term, stable and controllable NO release improves the therapeutic efficacy of cardiovascular stents. In this work, we developed a "one-pot" method inspired by mussel adhesive proteins for copolymerization of selenocystamine (SeCA) and dopamine (Dopa) to form a NO-generating coating on a 316 L stainless steel (SS) stent. This "one-pot" method is environmentally friendly and easy to popularize, with many advantages including simple manufacturing procedure, high stability and no involvement of organic solvents. Such SeCA/Dopa coatings also enabled us to develop a catalytic surface for local NO-generation by reaction of endogenously existing S-nitrothiol species from fresh blood. We found that the developed SeCA/Dopa coatings could release NO in a controllable and stable manner for more than 60 days. Additionally, the released NO significantly inhibited smooth muscle cell (SMC) proliferation and migration, as well as platelet activation and aggregation through the up-regulation of cyclic guanosine monophosphate synthesis. Moreover, such NO generation enhanced the adhesion, proliferation and migration of endothelial cells (ECs), and achieved rapid in vivo re-endothelialization, effectively reducing in-stent restenosis and neointimal hyperplasia. We envision that the SeCA/Dopa-coated 316 L SS stent could be a promising platform for treatment of cardiovascular diseases.

Topics: Animals; Bivalvia; Blood Circulation; Blood Platelets; Catalysis; Cell Adhesion; Cell Proliferation; Coated Materials, Biocompatible; Cyclic GMP; Cystamine; Dopamine; Gases; Human Umbilical Vein Endothelial Cells; Humans; Implants, Experimental; Myocytes, Smooth Muscle; Nitric Oxide; Organoselenium Compounds; Platelet-Rich Plasma; Rabbits; Stents; Thrombosis

Immobilization of selenocystamine on TiO(2) film deposited on silicon wafer and 316 stainless steel stents for catalytic generation of nitric oxide was described. Polydopamine was used as the linker for immobilization of selenocystamine to the TiO(2) surface. In vitro stability of the immobilized selenocystamine was investigated and the result shows surface selenium loss occurs mostly in the first four weeks. The selenocystamine immobilized surface possesses glutathione peroxidase (GPx) activity, and the activity increases with the amount of grafted polydopamine. Such selenocystamine immobilized surfaces show the ability of catalytically decomposing endogenous S-nitrosothiols (RSNO), generating NO; thus the surface displays the ability to inhibit collagen-induced platelet acitivation and aggregation. Additionally, smooth muscle cells are inhibited from adhering to the selenocystamine immobilized sample when RSNO is added to the culture media. ELISA analysis reveals that cGMP in both platelets and smooth muscle cells significantly increases with NO release on selenocystamine immobilized samples. Two months in vivo results show that selenocystamine immobilized stents are endothelialized, and show significant anti-proliferation properties, indicating that this is a favorable method for potential application in vascular stents.

Topics: Animals; Biocompatible Materials; Blood Platelets; Catalysis; Cell Adhesion; Cells, Cultured; Cyclic GMP; Cystamine; Dogs; Dopamine; Drug-Eluting Stents; Enzyme-Linked Immunosorbent Assay; Glutathione Peroxidase; Humans; Nitric Oxide; Organoselenium Compounds; S-Nitrosothiols; Spectroscopy, Fourier Transform Infrared; Titanium