Reciprocal regulation of NO signaling and TXNIP expression in humans: Impact of aging and ramipril therapy

Sverdlov, Aaron L., Chan, Wai P. A., Procter, Nathan E. K., Chirkov, Yuliy Y., Ngo, Doan T. M. and Horowitz, John D. (2013) Reciprocal regulation of NO signaling and TXNIP expression in humans: Impact of aging and ramipril therapy. International Journal of Cardiology, 168 (5). pp. 4624-4630. ISSN 0167-5273

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Abstract

Background: Impaired tissue responsiveness to nitric oxide (NO) occurs in many cardiovascular diseases as well as with advanced age and is a correlate of poor outcomes. This phenomenon results from oxidative stress, with NO “scavenging” and dysfunction of soluble guanylate cyclase (sGC). Thioredoxin-interacting protein (TXNIP) is a major intracellular regulator of inflammatory activation and redox stress, but its interactions with NO/sGC are poorly understood. We have now evaluated the relationship between platelet TXNIP expression and function of the NO/sGC axis in subjects of varying age and during therapy with ramipril. Methods & results: Young (n = 42) and aging (n = 49) subjects underwent evaluation of platelet TXNIP content. Aging subjects additionally had measurements of platelet NO responsiveness and routine biochemistry. Platelet TXNIP content was greater (376 ± 33 units) in the aging compared to younger subjects (289 ± 13 units; p < 0.05). In the aging subjects there was a significant negative correlation (r = − 0.50, p < 0.001) between platelet TXNIP content and NO responsiveness. In a separate cohort of 15 subjects two week treatment with ramipril, which reversed platelet NO resistance and potentiated sGC activity, also decreased platelet TXNIP content by 40% (p = 0.011). Conclusions: Platelet TXNIP content increases with aging, varies inversely with responsiveness to NO, and diminishes rapidly following treatment with ramipril. These data suggest that TXNIP-induced oxidative stress may be a critical modulator of tissue resistance to NO, a fundamental basis for cardiovascular disease. Analogously suppression of TXNIP expression can potentially be utilized as an index of restoration of cardiovascular homeostasis.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 19 Nov 2018 13:30
Last Modified: 22 Apr 2020 07:14
URI: https://ueaeprints.uea.ac.uk/id/eprint/68945
DOI: 10.1016/j.ijcard.2013.07.159

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