| First Author | Kratsios P | Year | 2010 |
| Journal | Circ Res | Volume | 106 |
| Issue | 1 | Pages | 133-44 |
| PubMed ID | 19850942 | Mgi Jnum | J:170139 |
| Mgi Id | MGI:4944040 | Doi | 10.1161/CIRCRESAHA.109.202200 |
| Citation | Kratsios P, et al. (2010) Antioxidant amelioration of dilated cardiomyopathy caused by conditional deletion of NEMO/IKKgamma in cardiomyocytes. Circ Res 106(1):133-44 |
| abstractText | RATIONALE: Insight into the function of nuclear factor (NF)-kappaB in the adult heart has been hampered by the embryonic lethality of constitutive NF-kappaB inactivation. OBJECTIVE: The goal of the present study was therefore to gain insights into the role of NF-kappaB pathway specifically in mouse cardiomyocytes by conditional deletion of the NF-kappaB essential modulator (NEMO). METHODS AND RESULTS: Using a Cre/loxP system, we disrupted the Nemo gene in a cardiomyocyte-specific manner in the heart, which simulated gene expression changes underlying human heart failure and caused adult-onset dilated cardiomyopathy accompanied by inflammation and apoptosis. Pressure overload challenges of NEMO-deficient young hearts precociously induced the functional decrements that develop spontaneously in older knockout animals. Moreover, oxidative stress in NEMO-deficient cardiomyocytes is a critical pathological component that can be attenuated with antioxidant diet in vivo. CONCLUSIONS: These results reveal an essential physiological role for NEMO-mediated signaling in the adult heart to maintain cardiac function in response to age-related or mechanical challenges, in part through modulation of oxidative stress. |
