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ABSTRACTIntroductionCardiac hypertrophy is associated with adverse outcomes across cardiovascular disease states. Despite strides over the last three decades in identifying molecular and cellular mechanisms driving hypertrophy, the link between pathophysiological stress stimuli and specific myocyte/heart growth profiles remains unclear. Moreover, the optimal strategy for preventing pathology in the setting of hypertrophy remains controversial.Areas CoveredThis review discusses molecular mechanisms underlying cardiac hypertrophy with a focus on factors driving the orientation of myocyte growth and the impact on heart function. We highlight recent work showing a novel role for the spectrin-based cytoskeleton, emphasizing regulation of myocyte dimensions but not hypertrophy per se. Finally, we consider opportunities for directing the orientation of myocyte growth in response to hypertrophic stimuli as an alternative therapeutic approach. Relevant publications on the topic were identified through Pubmed with open-ended search dates.Expert OpinionTo define new therapeutic avenues, more precision is required when describing changes in myocyte and heart structure/function in response to hypertrophic stimuli. Recent developments in computational modeling of hypertrophic networks, in concert with more refined experimental approaches will catalyze translational discovery to advance the field and further our understanding of cardiac hypertrophy and its relationship with heart disease.

ABSTRACTIntroduction: 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.