The sets of proteins secreted from cells, ie, secretomes, play crucial roles in intercellular and intertissue communication during tissue development and growth and in response to various pathological stresses. The secretomes produced by the heart encompass a group of proteins that have been referred to as cardiokines. In today’s era of molecular sophistication, the number of identified cardiokine candidates is steadily increasing as a result of the desire to identify new biomarkers and targets for cardiovascular disease treatment. It is widely recognized that the cells of the heart, including myocytes, fibroblasts, vascular cells, and progenitor cells, secrete various subsets of regulatory proteins in response to changes in the cardiac environment. 1–5 These secreted proteins are required for the maintenance of normal cardiac function, and they control pathological remodeling of the myocardium in response to injury through their ability to modulate myocyte death, fibroblast activation, inflammation, and vascular growth and regression. In addition, some of these factors function systematically, influencing kidney function or cachectic processes. Examples of well-known cardiokines include atrial natriuretic peptide and brain natriuretic peptide, which are synthesized mainly in the myocardium and upregulated in response to myocardial stretching. 6, 7 Both atrial natriuretic peptide and brain natriuretic peptide exert beneficial actions on cardiac remodeling by directly affecting cardiac cells in an autocrine and/or paracrine manner. In addition, atrial natriuretic peptide and brain natriuretic peptide influence electrolyte and water excretion in the kidney and regulate vascular tone and vascular cell growth via endocrine mechanisms. 7 Cardiac cells produce tumor necrosis factor-α and transforming growth factor-ß1 in pathological states, and these factors can promote pathological myocardial remodeling by promoting the recruitment of inflammatory cells or by facilitating hypertrophic growth and fibrosis. 8, 9 Under conditions of stress, the heart also produces angiotensin II, contributing to cardiac hypertrophy and fibrosis. Recent studies have shown that angiotensin II has a catabolic effect on skeletal muscle, suggesting that it may contribute to muscle wasting in congestive heart failure. 10, 11

Recently, a number of studies have used gene expression, array screening, cloning, and other techniques to identify new cardiokines and cardiokine networks that are regulated during cardiac stress. With mouse genetic approaches, many of these newly identified factors have been shown to have functional roles in pathological cardiac remodeling. The discovery and characterization of novel cardiokines are of interest because they will lead to a better mechanistic understanding of how alterations in cell-cell communication contribute to heart disease and could identify new diagnostic and therapeutic targets. This brief review focuses on the regulation and function of a few of the more recently identified cardiokines.