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Type: Journal article
Title: Reciprocal regulation of NO signaling and TXNIP expression in humans: Impact of aging and ramipril therapy
Author: Sverdlov, A.
Chan, W.
Procter, N.
Chirkov, Y.
Ngo, D.
Horowitz, J.
Citation: International Journal of Cardiology, 2013; 168(5):4624-4630
Publisher: Elsevier Sci Ireland Ltd
Issue Date: 2013
ISSN: 0167-5273
Statement of
Aaron L. Sverdlov, Wai P.A. Chan, Nathan E.K. Procter, Yuliy Y. Chirkov, Doan T.M. Ngo, John D. Horowitz
Abstract: <h4>Background</h4>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.<h4>Methods & results</h4>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).<h4>Conclusions</h4>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.
Keywords: Nitric oxide; Thioredoxin-interacting protein; ACE inhibitors; Aging; Platelets
Rights: Copyright © 2013 Published by Elsevier Ireland Ltd.
RMID: 0020132552
DOI: 10.1016/j.ijcard.2013.07.159
Appears in Collections:Medicine publications

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