Chips Ahoy

Abstract

Organ-level heart failure can result, most obviously, from the death of cardiac myocytes; such death can occur either acutely (with infarction) or more sporadically (in chronic disease). Both types of death can involve a “cell suicide” pathway known as apoptosis.1 Another key factor for cardiac dysfunction is myocardial fibrosis, which can be, in part, a direct consequence of angiotensin II levels; therefore, a possible benefit of therapy with angiotensin-converting enzyme inhibitors is an improvement in fibrosis. A third generic mechanism for defects in macroscopic or clinically evident cardiac performance arises from changes in the intrinsic mechanical properties of individual cardiac muscle cells.2 This phenomenon is understood to occur, in part, through changes in the expression of cardiac genes, both subtle and overt, which are collectively referred to as the hypertrophic gene “program.”3 Reprogramming cardiac gene expression encompasses, among its other features, alterations in (1) contractile proteins of the sarcomere, (2) regulators of calcium handling and other aspects of ion transport, and (3) secreted growth factors and cytokines. Therefore, in pursuit of potential targets for therapy, 2 important aspects of contemporary heart failure research are to discover the signaling pathways that confer adverse responses3 4 and to establish a much more comprehensive understanding of the end-organ changes that actually occur. In the current issue of Circulation , Yang et al5 performed a mammoth screen for altered gene expression in heart failure using a newly developed technology, high-density DNA microarrays.6 Although conceptually simple, these assays …