Stressed hearts inflame the body (in a good way)

Heart failure is a global health problem, with an estimated 30–50 million patients diagnosed worldwide (1, 2). Therapeutic advances have reduced early mortality; however, morbidity caused by damaged or failing ventricles remains high. Indeed, heart failure is the most common cause for hospitalization in elderly individuals, with recalcitrant 5-y survival rates remaining worse than most cancers (2). Sustained stress from abnormal mechanical load, neurohormone stimulation, and genetic defects are all potent inducers of heart failure (3, 4). These trigger conversations among vascular, muscle, and inflammatory cells, as well as fibroblasts using a myokine/cytokine vocabulary that can be shared by the multiple cell types or be more specific. As recently reviewed by Ghigo et al. (5), growing evidence has positioned the myocyte as a “Master and Commander” for coordinating interstitial responses to myocardial stress, including fibrosis, vascular remodeling, and inflammation. In hearts subjected to pressure overload, myocyte secretion of interleukins (IL-1β, -6, -18), TNF-α, receptor activator of NF-κB ligand, and macrophage chemoattractant protein-1 all signal to inflammatory responses, whereas ischemic disease engages additional factors, such as the adhesion molecules ICAM-1 and VCAM-1, and anti-inflammatory growth differentiation factor 15 (5). Depending on the stress, this coordinated inflammatory conversation can impact myocyte growth and survival, as well as remove damaged or dead cells. IL-33 is a member of the IL-1 superfamily and promotes inflammation in parasitic infection, bronchial asthma, rheumatoid arthritis, and sepsis (6, 7). ST2 was identified as an orphan receptor among the IL-1 receptor family and now it is known …