Deciphering STAT3 signaling in the heart: plasticity and vascular inflammation

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays a critical role in heart development and protection. New developments in understanding its molecular chemistry have revealed the importance of STAT3 in controlling mitochondrial respiration, independent of its function as a transcription factor, and in modulating inflammatory signaling through interactions with other transcription factors and cofactors. The purpose of this article is 2-fold. First, the authors summarize some recent insights into the function of STAT3. Second, the authors seek to illustrate the complexity of targeting a particular cellular protein for therapeutic purposes and the need to consider context when attempting to decipher the role of a particular signaling pathway in the heart. In this case, inflammation, aging, hypertrophy, and heart failure provide new environments that certainly impact on the functioning of STAT3 and on the gene profile linked to its activation.