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HomeCirculation ResearchVol. 108, No. 12In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Originally published10 Jun 2011https://doi.org/10.1161/RES.0b013e318224a335Circulation Research. 2011;108:1413PDGF Receptors and Epicardial EMT (p e15)Smith et al have investigated the origins of cardiac fibroblasts and discovered that PDGFα receptor plays a crucial role.Download figureDownload PowerPointIn the heart, the contractile cardiomyocytes may get most of the limelight, but they would be nothing without the supporting work of the endothelial cells, fibroblasts, and vascular smooth muscle cells (VSMCs). The latter two cell types are derived from a single source—epicardial cells of the early embryonic heart. In epicardial cells, two related receptors are expressed—PDGFα and β. Loss of PDGFβ results in the loss of VSMCs, which raises the obvious question—does loss of PDGFα result in loss of cardiac fibroblasts? The answer is yes. Smith et al made mice that lacked PDGFα or β, or both, in epicardial cells. Whereas the lack of α or β led to loss of fibroblasts or VSMCs, respectively, the loss of both led to a failure of epicardial cells to undergo epithelial-to-mesenchymal transition (EMT), an essential step before specific fates diverge. The authors also showed that the transcription factor Sox9 was downregulated in PDGF-lacking epicardium and that restoring Sox9 expression could restore EMT. Overproliferation of cardiac fibroblasts (cardiac fibrosis) is a major problem in long-term cardiac disease. Perhaps knowing how these cells form could offer new clues as to how to keep them under control.β3-ARs Mediate Exercise-Induced Cardioprotection (p 1448)The cardioprotective effects of exercise have long been appreciated, and now Calvert et al have discovered how it works.Download figureDownload PowerPointA number of factors have been implicated in exercise-associated protection against ischemic injury in the heart, but so far, evidence has been largely circumstantial. For example, nitric oxide (NO)—a potent cardiac protector—and its metabolites are increased in the blood during exercise, as are eNOS, the enzyme that drives NO synthesis, and stimulants of the β-adrenergic receptor (β-AR), which can activate eNOS. To understand the mechanics more fully, however, Calvert et al studied mice that lacked eNOS or β-AR. The mice were exercised for four weeks and then returned to a sedentary life for 24 hours, one week or four weeks before they were subjected to ischemia/reperfusion injury. Wild-type mice were protected from injury for at least a week after exercise cessation, whereas mice lacking eNOS or β-AR were not. The team also showed that exercise in wild-type mice increased NO metabolites in the heart itself, not just the blood, and this appeared to work through β-AR stimulation of eNOS. The findings not only reveal how exercise protects the heart, but also offer a number of possible targets for therapies aimed at protecting the heart from ischemia.Phosphatase-Resistant Gap Junctions (p 1459)Keeping connexin 43 protein phosphorylated and in its place can prevent arrhythmias, report Remo et al.Download figureDownload PowerPointConnexin 43 is one of the main proteins that form gap junctions—connections between heart cells that are essential for propagating impulses. Dysregulation of cell-to-cell coupling is thought to cause arrhythmias. Indeed, gap junction remodeling has been observed in a number of cardiac pathologies. To control the correct assembly, formation, and function of gap junctions, connexins are phosphorylated and dephosphorylated by a cadre of regulated kinases and phosphatases. Connexin 43 itself has twelve known phosphorylation sites. Although much has been learned about these sites and their function, the findings have come largely from in vitro studies. To start to unravel in vivo physiology, Remo et al made mice whose connexin 43 was either resistant to phosphorylation by a particular kinase, CK1δ, or permanently phosphorylated. The latter mice were protected from pathologic gap junction remodeling in response to stress (known to cause remodeling in wild-type mice) and to arrhythmias, whereas mice carrying the nonphosphorylatable form of connexin 43 were strongly susceptible to both. The authors, thus, suggest that modulation of connexin 43 phosphorylation may be a desirable approach for the treatment of arrhythmias.Written by Ruth Williams. Previous Back to top Next FiguresReferencesRelatedDetails June 10, 2011Vol 108, Issue 12 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/RES.0b013e318224a335 Originally publishedJune 10, 2011 PDF download Advertisement