Biomimetic-Structured Cobalt Nanocatalyst Suppresses Aortic Dissection Progression by Catalytic Antioxidation.
Bowen YangChengkai HuYuchong ZhangDi JiangPeng LinShouji QiuJianlin ShiLixin WangPublished in: Journal of the American Chemical Society (2024)
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.
Keyphrases
- aortic dissection
- reactive oxygen species
- oxidative stress
- electron transfer
- cardiovascular disease
- dna damage
- vascular smooth muscle cells
- cell death
- signaling pathway
- aortic valve
- stem cells
- type diabetes
- angiotensin ii
- mouse model
- transcription factor
- ischemia reperfusion injury
- gold nanoparticles
- heart failure
- atrial fibrillation
- endoplasmic reticulum stress
- tissue engineering
- density functional theory
- coronary artery
- molecular dynamics
- heat stress
- bone regeneration