Abstract
A deficiency of tetrahydrobiopterin (BH4), a critical cofactor for endothelial cell (EC) nitric oxide (NO) synthase, may be a common cause of vascular dysfunction in many diseases. Our goal was to augment BH4 levels in ECs in order to increase NO bioavailability and improve vascular function in streptozotocin‐induced diabetic rats. We encapsulated BH4 in biodegradable poly(D,L‐lactide‐co‐glycolide) nanoparticles (NPs) using an emulsion‐solvent evaporation method. Concentrations of BH4 in ECs and vessels were calculated using a reversed phase high‐performance liquid chromatography (HPLC) method after oxidation of samples under acidic and alkaline conditions, while nitrite levels were measured using an HPLC method developed in our lab. NO‐dependent relaxation of vessels was assessed by measuring the response to increasing concentrations of acetylcholine. NPs were taken up by ECs in a time‐and dose‐dependent fashion. BH4 levels in ECs and NO synthesis were increased after uptake of BH4‐loaded NPs. Importantly, BH4‐loaded NPs increased endothelium‐dependent vasodilatory responses of vessels from diabetic rats, demonstrating the ability of NP‐mediated BH4 delivery to restore vascular function. These studies support the feasibility of utilizing biodegradable NPs to deliver therapeutic agents to ECs to attenuate dysfunction associated with vascular disease. (Supported by NIH grant #HL093689).
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
