RT Book, Section A1 Hajjar, Roger J. A1 Ishikawa, Kiyotake A1 Thum, Thomas A2 Fuster, Valentin A2 Harrington, Robert A. A2 Narula, Jagat A2 Eapen, Zubin J. SR Print(0) ID 1161723541 T1 MOLECULAR AND CELLULAR BIOLOGY OF THE HEART T2 Hurst's The Heart, 14e YR 2017 FD 2017 PB McGraw-Hill Education PP New York, NY SN 9780071843249 LK accesscardiology.mhmedical.com/content.aspx?aid=1161723541 RD 2024/03/29 AB Biology of the heart is meticulously orchestrated by various mechanisms, including receptor-mediated signal transduction, post-translational modification, protein degradation, and transcriptional regulation. To maintain the hemodynamic homeostasis, the heart uses these processes in a chronologically regulated manner. Because the time between heart beats is usually less than one second, instant changes in the body blood demand must be rapidly adapted. This is achieved by modifying β-adrenergic signaling and subsequent phosphorylation/dephosphorylation of proteins related to excitation–contraction coupling. In contrast, chronically altered hemodynamic status, such as hypertension, is adapted via network of signal transductions leading to reprogramming of the gene expression. Emerging evidence indicates that microRNAs, long noncoding RNAs, or circular RNAs are also critically involved in these transcriptional regulations. Sustained activation of certain pathways initially induces adaptive responses but eventually become maladaptive, causing pathological hypertrophy, contractile dysfunction, cell loss, and extracellular remodeling. These changes are clinically represented as heart failure and predispose patients to increased morbidity and mortality. With the rapid advances in the development of small molecule inhibitors and gene therapy approaches that can possibly target key pathological pathways in vivo, we are approaching the point of being able to readily manipulate these pathways in patients. Noncoding RNAs not only play crucial roles in orchestrating the genome and cellular pathways but also can be used as novel therapeutic targets and diagnostic markers. Therefore, understanding the molecular mechanisms governing cardiac pathophysiology is essential to understanding the signaling networks that regulate heart failure development. In this chapter, we will highlight the role of important regulators and biological molecular principles in cardiac homeostasis and disease.