| First Author | Zhang XQ | Year | 2013 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 305 |
| Issue | 7 | Pages | H1089-97 |
| PubMed ID | 23913709 | Mgi Jnum | J:202866 |
| Mgi Id | MGI:5522628 | Doi | 10.1152/ajpheart.00067.2013 |
| Citation | Zhang XQ, et al. (2013) Cardiomyocyte-specific p65 NF-kappaB deletion protects the injured heart by preservation of calcium handling. Am J Physiol Heart Circ Physiol 305(7):H1089-97 |
| abstractText | NF-kappaB is a well-known transcription factor that is intimately involved with inflammation and immunity. We have previously shown that NF-kappaB promotes inflammatory events and mediates adverse cardiac remodeling following ischemia reperfusion (I/R). Conversely, others have pointed to the beneficial influence of NF-kappaB in I/R injury related to its anti-apoptotic effects. Understanding the seemingly disparate influence of manipulating NF-kappaB is hindered, in part, by current approaches that only indirectly interfere with the function of its most transcriptionally active unit, p65 NF-kappaB. Mice were generated with cardiomyocyte-specific deletion of p65 NF-kappaB. Phenotypically, these mice and their hearts appeared normal. Basal and stimulated p65 expression were significantly reduced in whole hearts and completely ablated in isolated cardiomyocytes. When compared with wild-type mice, transgenic animals were protected from both global I/R by Langendorff as well as regional I/R by coronary ligation and release. The protected, transgenic hearts had less cytokine activity and decreased apoptosis. Furthermore, p65 ablation was associated with enhanced calcium reuptake by the sarcoplasmic reticulum. This influence on calcium handling was related to increased expression of phosphorylated phospholamban in conditional p65 null mice. In conclusion, cardiomyocyte-specific deletion of the most active, canonical NF-kappaB subunit affords cardioprotection to both global and regional I/R injury. The beneficial effects of NF-kappaB inhibition are related, in part, to modulation of intracellular calcium homeostasis. |
