| 摘要 |
<p>We have established a heart slice primary culture system that allows the mechanical separation of distinct cardiac cell populations and the assay of their relative mitogenic and trophic effects on cardiomyocyte proliferation and survival. Using this system, we have found that a signals from the epicardium, but not the trabeculae and endocardium, is required in heart slices for continued myocyte proliferation and survival. Blockade of retinoic acid (RA) signaling from the epicardium inhibits cardiomyocyte proliferation and survival. Interestingly, this inhibition is reversed by the addition of another epicardial secreted factor, erythropoietin (Epo). These factors do not act directly on myocardial cells, but rather induce yet another soluble epicardial factor that directly rescues proliferation of cardiomyocytes. Thus, the epicardium controls normal heart growth in ventricular segments of the heart by secreting a cardiomyocyte mitogen whose expression or activity is regulated by both RA and erythropoietin signaling within the epicardium.</p> |
