Theranostics 2022; 12(11):5189-5203. doi:10.7150/thno.71813 This issue Cite

Review

The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications

Kailun Phua1*, Nicholas WS Chew1*✉, William KF Kong1, Ru-San Tan2, Lei Ye3, Kian-Keong Poh1,4✉

1. Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
2. Department of Cardiology, National Heart Centre Singapore, Singapore, 169609, Singapore
3. National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, 169609, Singapore
4. Yong Loo Lin School of Medicine, National University of Singapore, Singapore
* These 2 authors contributed equally as co-first authors

Citation:
Phua K, Chew NWS, Kong WKF, Tan RS, Ye L, Poh KK. The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications. Theranostics 2022; 12(11):5189-5203. doi:10.7150/thno.71813. https://www.thno.org/v12p5189.htm
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Abstract

Graphic abstract

Despite the elucidation of the pathways behind the development of aortic stenosis (AS), there remains no effective medical treatment to slow or reverse its progress. Instead, the gold standard of care in severe or symptomatic AS is replacement of the aortic valve. Oxidative stress is implicated, both directly as well as indirectly, in lipid infiltration, inflammation and fibro-calcification, all of which are key processes underlying the pathophysiology of degenerative AS. This culminates in the breakdown of the extracellular matrix, differentiation of the valvular interstitial cells into an osteogenic phenotype, and finally, calcium deposition as well as thickening of the aortic valve. Oxidative stress is thus a promising and potential therapeutic target for the treatment of AS. Several studies focusing on the mitigation of oxidative stress in the context of AS have shown some success in animal and in vitro models, however similar benefits have yet to be seen in clinical trials. Statin therapy, once thought to be the key to the treatment of AS, has yielded disappointing results, however newer lipid lowering therapies may hold some promise. Other potential therapies, such as manipulation of microRNAs, blockade of the renin-angiotensin-aldosterone system and the use of dipeptidylpeptidase-4 inhibitors will also be reviewed.

Keywords: Severe aortic stenosis, reactive oxidative species, oxidative stress


Citation styles

APA
Phua, K., Chew, N.WS., Kong, W.KF., Tan, R.S., Ye, L., Poh, K.K. (2022). The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications. Theranostics, 12(11), 5189-5203. https://doi.org/10.7150/thno.71813.

ACS
Phua, K.; Chew, N.WS.; Kong, W.KF.; Tan, R.S.; Ye, L.; Poh, K.K. The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications. Theranostics 2022, 12 (11), 5189-5203. DOI: 10.7150/thno.71813.

NLM
Phua K, Chew NWS, Kong WKF, Tan RS, Ye L, Poh KK. The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications. Theranostics 2022; 12(11):5189-5203. doi:10.7150/thno.71813. https://www.thno.org/v12p5189.htm

CSE
Phua K, Chew NWS, Kong WKF, Tan RS, Ye L, Poh KK. 2022. The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications. Theranostics. 12(11):5189-5203.

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