期刊
CIRCULATION RESEARCH
卷 128, 期 7, 页码 993-1020出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.121.318063
关键词
antioxidants; biomarkers; endoplasmic reticulum stress; hydrogen peroxide; reactive oxygen species
资金
- National Institutes of Health (NIH) [HL152167]
- British Heart Foundation [RE/18/6/34217, CH/4/29762]
- University of Glasgow Walton Fellowship
The link between oxidative stress and hypertension has been established in animal models, but remains elusive in humans. Research has expanded our understanding of reactive oxygen species and their impact on signaling pathways, with potential for developing novel antihypertensive therapies.
A link between oxidative stress and hypertension has been firmly established in multiple animal models of hypertension but remains elusive in humans. While initial studies focused on inactivation of nitric oxide by superoxide, our understanding of relevant reactive oxygen species (superoxide, hydrogen peroxide, and peroxynitrite) and how they modify complex signaling pathways to promote hypertension has expanded significantly. In this review, we summarize recent advances in delineating the primary and secondary sources of reactive oxygen species (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial nitric oxide synthase, endoplasmic reticulum, and mitochondria), the posttranslational oxidative modifications they induce on protein targets important for redox signaling, their interplay with endogenous antioxidant systems, and the role of inflammasome activation and endoplasmic reticular stress in the development of hypertension. We highlight how oxidative stress in different organ systems contributes to hypertension, describe new animal models that have clarified the importance of specific proteins, and discuss clinical studies that shed light on how these processes and pathways are altered in human hypertension. Finally, we focus on the promise of redox proteomics and systems biology to help us fully understand the relationship between ROS and hypertension and their potential for designing and evaluating novel antihypertensive therapies.
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