Details

Autor(en) / Beteiligte

• Sverdlov, Aaron L
• Chan, Wai P.A
• Procter, Nathan E.K
• Chirkov, Yuliy Y
• Ngo, Doan T.M
• Horowitz, John D

Titel

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

Ist Teil von

• International journal of cardiology, 2013-10, Vol.168 (5), p.4624-4630

Ort / Verlag

Shannon: Elsevier

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.