1. Dichloroacetate inhibits the degeneration of decellularized cardiovascular implants
- Author
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Sentaro Nakanishi, A. Assmann, Mahfuza Toshmatova, Payam Akhyari, Yukiharu Sugimura, Alexander Assmann, Agunda Chekhoeva, and Artur Lichtenberg
- Subjects
Graft degeneration ,Pulmonary and Respiratory Medicine ,Neointima ,medicine.medical_specialty ,Eacts/166 ,Urology ,Dichloroacetate ,Vascular graft ,Anastomosis ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Translational Research ,medicine ,Animals ,Humans ,Tissue engineering ,Aorta, Abdominal ,Von Kossa stain ,Decellularization ,Eacts/114 ,030304 developmental biology ,Bioprosthesis ,0303 health sciences ,Hyperplasia ,AcademicSubjects/MED00920 ,business.industry ,Histology ,General Medicine ,medicine.disease ,Blood Vessel Prosthesis ,Rats ,Endothelial stem cell ,Intima hyperplasia ,030220 oncology & carcinogenesis ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Eacts/123 ,Calcification - Abstract
OBJECTIVES Intima hyperplasia is a major issue of biological cardiovascular grafts resulting in progressive in vivo degeneration that particularly decreases the durability of coronary and peripheral vascular bypasses. Previously, dichloroacetate (DCA) has been reported to prevent the formation of hyperplastic intima in injured arteries. In this study, the effect of DCA on the neointima formation and degeneration of decellularized small-caliber implants was investigated in a rat model. METHODS Donor rat aortic grafts (n = 22) were decellularized by a detergent-based technique, surface-coated with fibronectin (50 µl ml−1, 24 h incubation) and implanted via anastomoses to the infrarenal aorta of the recipients. Rats in the DCA group (n = 12) received DCA via drinking water during the whole follow-up period (0.75 g l−1), while rats without DCA treatment served as controls (n = 10). At 2 (n = 6 + 5) and 8 (n = 6 + 5) weeks, the grafts were explanted and examined by histology and immunofluorescence. RESULTS Systemic DCA treatment inhibited neointima hyperplasia, resulting in a significantly reduced intima-to-media ratio (median 0.78 [interquartile range, 0.51–1.27] vs 1.49 [0.67–2.39] without DCA, P, Tissue-engineered vascular grafts represent an implant source that promises to overcome the limitations of clinical standard grafts.
- Published
- 2021
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