Nrf2 deficiency aggravates Angiotensin II-induced cardiac injury by increasing hypertrophy and enhancing IL-6/STAT3-dependent inflammation

ConclusionOur results show that Nrf2 is important for the protection of the heart against Ang II-induced cardiac hypertrophy and inflammation by mechanisms involving the regulation of IL-6/STAT3-dependent signaling.Graphical abstractSchematic diagram showing the role of Nrf2 in cardiomyocytes during Ang II-induced Injury. Ang II up-regulates the expression of Nrf2, which in turn facilitates the transcription of genes associated with anti-oxidative stress, including SOD, HO-1, NQO-1 etc., and inhibits MEF2A transcription, which plays key roles during cardiac hypertrophy. Moreover, Ang II also promotes the secretion of IL-6, which enhances the activation of STAT3 and its downstream genes associated with inflammation. Up-regulation of these genes will finally results in cardiomyocyte inflammatory injury. During Ang II-induced activation of IL-6/STAT3 signaling pathway, Nrf2 inhibits IL-6 secretion, which in turn diminishes activation of STAT3 and suppresses expression of inflammatory factors including TNFα and IL-10, during Ang II stimulation, therefore alleviates Ang II-induced cardiomyocyte inflammation. When Nrf2 is deficient, increased oxidative stress, hypertrophy and inflammation in the myocardium will lead to cardiac fibrosis, hypertrophy and dysfunction, which finally results in heart failure.

Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - January 20, 2019 Category: Molecular Biology Source Type: research