Echocardiographic Strain Analysis in Mice (p 908)
A new echocardiographic technique for mice provides a better picture of heart function, report Bauer et al.
The standard procedure for assessing cardiac function in vivo is echocardiography, but this technique has limited resolution in humans, let alone small-model organisms like mice. Recently, two techniques have been developed to improve the accuracy of echocardiographic imaging in humans: strain analysis, which measures the change in size of particular heart regions, and speckle-tracking, in which specific small features (speckles) are tracked from frame to frame to improve the accuracy of strain measurements. Together, these techniques could also offer a feasible approach for accurate cardiac functional analysis in mice. To test this, Bauer et al induced heart attacks in adult mice and then measured cardiac function using the new techniques. Left ventricular measurements were considerably more sensitive using speckle-tracking strain analysis than standard echocardiography. Furthermore, the new techniques could detect subtle improvements following therapy as soon as two weeks after treatment; whereas standard echocardiography did not detect improvement even after six weeks. The ability to quickly and accurately measure cardiac function in mice will enable not only accurate assessment of new cardiac therapies, but also detection of subtle phenotypic differences between genetic model strains.
Hand2 Plays a Novel Role in Epicardiogenesis (p 940)
Barnes et al have uncovered a new role in cardiogenesis for the transcription factor, Hand2.
Hand1 and Hand2 are critical transcription factors for the correct development of the vertebrate heart. The two related factors are largely responsible for the morphogenesis of separate tissues and structures in the heart and only partially overlap in their expression pattern. Indeed, although mouse knockouts of either factor both die at around day 9.5 of embryogenesis, they display factor-specific tissue defects. Barnes et al were most interested in the heart cells in which Hand1 and −2 expressions do overlap. They devised a Hand1-specific Hand2 knockout—that is, the knockout of Hand2 only occurred in cells expressing Hand1. Importantly, these embryos survived until day 14.5 of embryogenesis, allowing Hand2's role to be assessed later in development. Mice with this conditional knockout failed to develop a proper epicardium and coronary vasculature (which is formed, in part, from epicardial cells). This role in epicardial development was hitherto unknown for Hand2. Given Hand1's and −2's essential role in cardiogenesis, the two factors and their pathways are implicated as mediators of congenital heart disease. The study by Barnes et al thus offers further insight into the factors' normal functions in cardiogenesis and possible ways the process could go wrong.
Atherosclerotic Plaque Alternative Macrophages (p 985)
Chinetti-Gbaguidi et al identify a population of macrophage do-gooders at atherosclerotic plaques.
As part of the pathologic process of atherosclerosis, monocytes infiltrate the plaque and develop into specialized fat-filled macrophages, called foam cells. Although foam cells are not problematic individually, their accumulation is detrimental, and it contributes to plaque growth and local inflammation. Monocyte-to-macrophage development can occur by both classic and alternative pathways. Classic activation produces M1 macrophages, which are known to be capable of developing into foam cells. Alternative activation produces M2 macrophages, which have also been found at plaques, though their function there was unknown. Chinetti-Gbaguidi et al discovered that M2 cells at atherosclerotic plaques had far less proclivity for foam cell formation and contained far less fat. Instead, their main occupation seemed to be phagocytosis—they gobbled up more apoptotic cells and debris than their M1 counterparts. Unlike M1 cells, M2 cells are known to produce antiinflammatory signals. Thus, the presence of these antiinflammatory, foam cell-resistant, phagocytosing M2 macrophages at atherosclerotic plaques could well be beneficial. Perhaps boosting their numbers may be a therapeutic avenue worth investigating.
Written by Ruth Williams
- © 2011 American Heart Association, Inc.