Abstract 15948: Inhibition of NF-kB Signaling Attenuates Age-related Aggravation of Myocardial Ischemia/Reperfusion Injury
Introduction: Emerging evidence indicates that myocardial ischemia/reperfusion (I/R) injury is more severe in aged hearts. Although nuclear factor-kappaB (NF-kB) activity increases with aging, whether this redox-responsive transcription factor plays any role in age-related worsening of I/R injury remains unknown.
Hypothesis: We hypothesized that activation of myocardial NF-kB exerts deleterious effects during I/R injury in young as well as aged hearts; and that NF-kB signaling contributes to age-related worsening of myocardial I/R injury.
Methods: We used transgenic mice overexpressing a mutant IkBa that prevents NF-kB activation only in the heart. Age-matched young (10-week-old) and aged (86-week-old) male non-transgenic littermates (NTg) and IkBa transgenic (Tg) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Following sacrifice, infarct size was measured and molecular assays were performed.
Results: The infarct size was significantly smaller in young Tg mice compared with young NTg mice (Fig), indicating a deleterious role of NF-kB signaling during myocardial I/R injury even in the young. The infarct size in aged NTg hearts was greater compared with young NTg hearts, consistent with an age-related worsening of I/R injury effects. However, infarct size in aged Tg hearts was significantly smaller than aged NTg hearts, and similar to young Tg hearts, indicating that NF-kB signaling contributes toward age-related aggravation of I/R injury. Interestingly, the levels of molecular markers of senescence, such as p16, were lower in aged Tg hearts (Fig), indicating a deleterious role of NF-kB in cardiac aging and susceptibility to I/R injury.
Conclusions: We conclude that inhibition of cardiac NF-kB signaling protects against age-related aggravation of acute myocardial I/R injury. These findings suggest that modulation of NF-kB signaling may be potentially used to achieve therapeutic cardioprotection in the elderly.
Author Disclosures: G. Cheng: None. S. Ye: None. M. Girgis: None. L. Zhao: None. X. Chen: None. A. Samanta: None. Y. Yang: None. J. Hauptman: None. R. Vincent: None. B. Dawn: None.
- © 2015 by American Heart Association, Inc.