Aging and GATA3-positive macrophages

Cardiovascular disease is currently recognized as the leading cause of morbidity and mortality in the adult population worldwide, with an estimated projection of 23.3 million yearly deaths attributable to these disorders by the year 2030 [1]. Although numerous studies in the cardiovascular field have considered humans, both young and old, there remain many unanswered questions about the contribution of genetic pathways in the regulation of aging in model organisms that also influence cardiovascular aging. Chronic inflammation is believed to contribute to the pathogenesis of many age-related diseases including cardiovascular disease. Chronic inflammation, particularly from activation of innate immunity, is highly sensitive to changes in the tissue environment that is associated with aging. The immune cell type that is particularly influenced by changes in its microenvironment is the monocyte/macrophage. These cells display a high level of plasticity and heterogeneity in response to their environmental cues. For example, based on the response of cultured macrophages to treatment with IL-4 or interferon γ, cells have been proposed to polarize to either M2 or M1 phenotypes, respectively. Although the M1-M2 polarization concept is useful in describing the two extremes of macrophage phenotypes, the concept does not accurately recapitulate the complex response of cells to their driving tissue microenvironment in vivo. In most animal models of tissue injury including the myocardial injury, the first phase involves infiltration of pro-inflammatory Ly6C monocytes followed by a decline in their numbers with a concomitant increase in the anti-inflammatory/reparative Ly6C cell subset. A timely resolution of each step in the recruitment of these cells is crucial since exuberant and prolonged inflammation and/or fibrosis may be deleterious and determines whether progression to cardiac tissue repair or heart failure occurs. The plasticity of monocytes/macrophages are determined by the constellation of transcription factors that are activated and expressed in response to environmental cues. To understand the role of GATA3 transcription factor in the pathogenesis of cardiac diseases, we generated myeloid-specific GATA3 knockout mice and found that their cardiac function is significantly improved in response to ischemia or pressure overload compared with the GATA3 sufficient Editorial