Cardiac myofibroblasts: cells out of balance. A new thematic series

Koyaanisqatsi is a Hopi word meaning “life out of balance” and is the title of the popular environmentalist movie shot nearly 2 decades ago. The film contrasts speeded-up images of American desert landscapes and life without man to smokestacks and expressways and an endless flow of humanity through the streets of any large city. The movie is beautifully created and supported by technical excellence in imagery and sound, to the point where one might make an honest mistake and misinterpret the main message, as indeed some of the images that were intended to repel to the viewer are appealing themselves. Using this representation of despoiled environment as an allegory of the presence of fibroblasts and their role in pathogenesis of fibrotic heart disease, the connection may be more easily discerned. In this regard, our laboratory has used an in vitro scratch assay and has compiled data depicting a greatly accelerated account of a 16-h duration showing migration of activated myofibroblasts (Additional file 1: Figure？1). Others have aptly described this assay as a “heart attack in a plate,” which is a convenient and inexpensive method to assess myofibroblast migration from the highly confluent area of cells into the denuded region [1]. In this figure, virtually all of the cells in the area photographed are myofibroblasts. Studying the film loop of myofibroblasts reveals a number of interesting phenomena. Cells in proximity to the denuded region become suddenly motile, and they reorient, divide, and migrate at greatly accelerated velocity vs. their relatively quiescent neighbors. While their movement from an area of relative confluence to the denuded area is fascinating in itself, it is likely a reasonably accurate reflection of their motility in vivo, e.g., in ongoing wound healing of necrosed muscle in post-MI heart and/or stroma. We have previously shown that cardiac myofibroblasts are hypersynthetic and are key players in the development of cardiac fibrosis. As such,