Emerging therapeutic targets for cardiac arrhythmias: role of STAT3 in regulating cardiac fibroblast function

Introduction : Cardiac fibrosis contributes to the development of cardiovascular disease (CVD) and arrhythmia. Cardiac fibroblasts (CFs) are collagen-producing cells that regulate extracellular matrix (ECM) homeostasis. A complex signaling network has been defined linking environmental stress to changes in CF function and fibrosis. Signal Transducer and Activator of Transcription 3 (STAT3) has emerged as a critical integrator of pro-fibrotic signals in CFs downstream of several established signaling networks. Areas covered : This article provides an overview of STAT3 function in CFs and its involvement in coordinating a vast web of intracellular pro-fibrotic signaling molecules and transcription factors. We highlight recent work elucidating a critical role for the fibroblast cytoskeleton in maintaining spatial and temporal control of STAT3-related signaling . Finally, we discuss potential opportunities and obstacles for therapeutic targeting of STAT3 to modulate cardiac fibrosis and arrhythmias. Relevant publications on the topic were identified through Pubmed. Expert opinion : Therapeutic targeting of STAT3 for CVD and arrhythmias presents unique challenges and opportunities. Thus, it is critical to consider the multimodal and dynamic nature of STAT3 signaling. Going forward, it will be beneficial to consider ways to maintain balanced STAT3 function, rather than large-scale perturbations in STAT3 function.