In This Issue

Abstract

HomeCirculation ResearchVol. 113, No. 5In This Issue Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBIn This Issue Originally published16 Aug 2013https://doi.org/10.1161/RES.0b013e3182a71457Circulation Research. 2013;113:479Dyssynchrony in Cytosolic Ca2+ Decay (p 527)Download figureDownload PowerPointHeart cells clear up their cytoplasmic calcium somewhat dyssynchronously, say Hohendanner et al, and this dyssynchrony gets worse in failing hearts.Calcium is the major intracellular regulator of cardiomyocyte contraction. It is released from its intracellular storage site, the sarcoplasmic reticulum, into the cytoplasm where it then activates the contractile machinery. But after each contraction, the cell must relax—a process that requires the prompt and efficient removal of calcium from the cytosol. This combined release and clear up of calcium is known as a calcium transient. It has been shown that the release of calcium across the cell is synchronized to ensure coordinated control of the contractile machinery, but less is known about the clean-up, or decay phase. Hohendanner and colleagues now show that calcium removal occurs at different microdomains throughout the cell and that the speed of decay varies from domain to domain. Furthermore, the rate of relaxation at adjacent contractile machinery varies in concordance with the differing decay rates of the domains. They also found that the degree of dyssynchrony is vastly exaggerated in failing human hearts as well as in mice with hypertrophy and pigs with chronic myocardial ischemia. This, increased dyssynchrony slows down the overall rate of relaxation and, the authors suggest that it might contribute to contractile dysfunction associated with cardiac hypertrophy and heart failure.Bone-Derived Stem Cells Repair the Heart (p 539)Download figureDownload PowerPointBelieve it or not, bone stem cells are better than cardiac stem cells for repairing a damaged heart, say Duran et al.While stem cell therapy is a promising approach for repairing damaged hearts, the results obtained to-date have been modest. Part of the problem is that different types of stem cells yield different results and the precise mechanisms underlying the beneficial effects of stem cells remain unclear. Thus, Duran and colleagues examined two mechanisms of repair—differentiation of stem cells into cardiac cell types and secretion of paracrine factors—in two different stem cell types, one from cortical bone and another from the heart. They found that when injected into damaged mouse hearts, the bone cells were actually more adept at differentiating into cardiac cell types—including cardiomyocytes, vascular endothelial cells, and smooth muscle cells—than the heart-derived cells, which only differentiated into immature cardiomyocytes. Cells from the bone also displayed sustained expression of pro-angiogenic paracrine factors, which correlated with better neovascularization of the damaged hearts. Cardiac stem cells, on the other hand, produced similar paracrine factors but only for one day after injection. Importantly, the better performance by the bone cells translated to improved heart function and increased survival for the mice, suggesting that the use of these cells might improve outcomes of cell therapy.IKK2 is a Myosin Light Chain Kinase (p 562)Download figureDownload PowerPointYing et al identify a possible new target for treating hypertension.Constriction of vascular smooth muscle cells (VSMCs), which contributes to hypertension, is controlled in part by phosphorylation of the myosin light chain (MLC). This post-translational modification enables actin and myosin molecules of the contractile machinery to interact and initiate contraction. MLC is known to be phosphorylated by MLCK but recent work suggests that at least one other kinase may be involved. For example, it has been observed that inhibition of MLCK does not lead to the complete dephosphorylation of MLC and that in MLCK-deficient mice, blood vessels remain responsive to vasoconstrictors. In addition, previous work has shown that the kinase IKK2 regulates migration and morphology in mouse embryonic fibroblasts, and that both of these processes depend on MLC phosphorylation. This led Ying and colleagues to ask whether IKK2 could be an MLC kinase in VSMCs. They found that not only was MLC phosphorylated by IKK2 in vitro and but also overexpression of IKK2 in VSMCs led to increased MLC phosphorylation. Conversely, inhibition of IKK2 decreased MLC phosphorylation and attenuated vasoconstrictive responses of isolated rat aortas. Furthermore, mice that lacked IKK2 in their VSMCs showed a decreased hypertensive response to three different vasoconstrictors. These results suggest that IKK2 inhibition could be a novel approach for decreasing hypertension. Previous Back to top Next FiguresReferencesRelatedDetails August 16, 2013Vol 113, Issue 5 Advertisement Article InformationMetrics © 2013 American Heart Association, Inc.https://doi.org/10.1161/RES.0b013e3182a71457 Originally publishedAugust 16, 2013 PDF download Advertisement