Cardiac remodeling in heart disease and the importance of thyroid hormones

Cardiac remodeling is the process of adaptive or maladaptive growth of the heart in response to altered loading conditions or growth stimuli. A landmark review by Linzbach in 1960 and reports by Grant (1965) and Grossman (1975) brought attention to anatomical remodeling of the heart in cardiac hypertrophy and heart failure (HF). This was largely the age of cardiac physiology with many focusing on in vivo and in vitro studies in animal models of heart disease. The neurohormonal hypothesis became a major driving force with realization that plasma norepinephrine levels increase with progression to HF. This led drug companies to develop compounds aimed at these targets. Prior to the discovery of angiotensin converting enzyme (ACE) inhibitors, available drugs offered symptomatic relief but had little effect on mortality. Cardiac remodeling became a hot area of HF research in the late 1980s and early 1990s. This field took off when investigators observed that reductions in mortality by neurohormonal inhibition in HF were intimately linked to beneficial changes in cardiac anatomy. More recent work, highlights the critical role of thyroid hormones (THs) in maintaining myocyte shape and internal myocyte structures involved in calcium handling. This overview focuses on the role of myocyte remodeling related to chamber remodeling and wall stress. Another goal was to provide technical advice and information for researchers to improve critical analysis of data in this area of research. A comprehensive understanding of the molecular basis of myocyte remodeling is evolving and would require a separate communication to address.