The p65 subunit of NF-κB involves in RIP140-mediated inflammatory and metabolic dysregulation in cardiomyocytes

• Elevated NF-κB activity in neonatal rat cardiomyocytes overexpressing RIP140.
• RIP140 impacts proinflammatory response of cardiomyocytes via p65-NF-κB pathway.
• p65-NF-κB is involved in RIP140-induced metabolic dysregulation in cardiomyocytes.

The transcription factor NF-κB regulates expression of many genes that are involved in inflammation, fatty acid and glucose metabolism, and plays a crucial role in cardiac pathological processes. RIP140 is a corepressor that down-regulates expression of genes involved in the cellular substrate uptake and mitochondrial β-oxidation. In addition to this, RIP140 also acts as a coactivator for p65-NF-κB, potentiating the secretion of proinflammatory cytokines in macrophages, but the effects in cardiomyocytes are still unknown. In this study, overexpression of RIP140 induced proinflammatory gene expression and cytokine release in neonatal rat cardiomyocytes, which could be reversed by p65-NF-κB inhibition. Furthermore, RIP140-mediated repression of metabolic-related genes, mitochondrial biogenesis and metabolic function were weakened after knocking down of p65-NF-κB. These findings suggest that p65-NF-κB plays an important role in RIP140-mediated proinflammatory response and energy metabolism in cardiomyocytes, and provide evidence for the crosstalk between proinflammatory processes and metabolic dysregulation in the heart.

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