In search of the proteins that cause myocardial stunning.

Cardiac diseases are characterized by a host of changes to the cellular processes that affect contractility of the heart. One emerging experimental approach to the study of cardiac disease, including the ischemia/reperfusion injury known as stunning, is to identify proteins that have been specifically altered or modified in the diseased state. Minimally, the identification of modified proteins will provide new diagnostic markers of myocyte injury. However, for a subset of proteins, disease-induced modification will substantively affect molecular function and contribute directly to cardiac dysfunction. Identification of these causative proteins will ultimately prove beneficial to the design of new pharmacological, genetic, or peptidomimetic therapies. The complement and status of proteins within a myocyte (its protein profile) may be altered, through gene-mediated processes, which include isoform switching and the capacity to vary levels of protein expression, or through posttranslational modification, which includes phosphorylation and proteolysis among other processes. Protein function can also be perturbed under conditions of altered cellular homeostasis, which range from oxidative stress to cellular acidosis. In chronic disease, such as heart failure, the complexity of ongoing adaptive changes to cardiac function is mirrored at the molecular level. As a result, many, possibly hundreds of, proteins are subject to altered expression and/or posttranslational modification. In the acute phase of disease, however, dysfunction often precedes gene-mediated adaptive response, which suggests that the mechanism that underlies acute cardiac injury is attributable to a select few posttranslational events. This could well be the case for myocardial stunning, the subject of the article by Thomas et al1 in this issue of Circulation Research.