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1.
J Am Chem Soc ; 146(25): 17201-17210, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38874405

RESUMEN

As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.


Asunto(s)
Antioxidantes , Disección Aórtica , Cobalto , Catálisis , Cobalto/química , Cobalto/farmacología , Disección Aórtica/tratamiento farmacológico , Disección Aórtica/patología , Antioxidantes/química , Antioxidantes/farmacología , Animales , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Ratones , Especies Reactivas de Oxígeno/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacos , Nanopartículas del Metal/química
2.
Int J Biol Macromol ; 253(Pt 1): 126598, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37660861

RESUMEN

The low patency rate after artificial blood vessel replacement is mainly due to the ineffective use of anticoagulant factors and the mismatch of mechanical compliance after transplantation. Electrospun nanofibers with biomimetic extracellular matrix three-dimensional structure and tunable mechanical strength are excellent carriers for heparin. In this work, we have designed and synthesized a series of biodegradable poly(ester-ether-urethane)ureas (BEPU), following compound with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid BEPU/heparin nanofibers tubular graft for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The results in vitro demonstrated that the electrospun L-PEUUH (LDI-based PEUU with heparin) vascular graft was of regular microstructure, optimum surface wettability, matched mechanical properties, reliable cytocompatibility, and strongest endothelialization in situ. Replacement of resected abdominal artery with the L-PEUUH vascular graft in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), as well as stabilizing the blood microenvironment. This research demonstrates the L-PEUUH vascular graft with substantial patency, indicating their potential for injured vascular healing.


Asunto(s)
Prótesis Vascular , Células Endoteliales , Ratas , Animales , Heparina/química , Anticoagulantes , Biomimética , Poliésteres/química
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