Larry Gilbert posted an update 1 week, 3 days ago
To our knowledge, for the first time, the crystal formation and the possible role of Mg2+ in VC through an in vitro model of primary human aortic vascular smooth muscle cells was investigated in this study. At this point, we have to underline that usual methods to gather information on the chemical nature of VC are based on staining procedures which display several limitations for identifying and quantifying apatite. All these limitations call for the need to combine usual techniques with physical techniques such as Scanning Electron Microscopy, Micro-Computerized Tomography, Micro-Fourier Transform InfraRed, RAMAN spectroscopies and X-ray fluorescence or X-ray scattering. In this report, we developed an experimental procedure to culture cells on a support that was suitable to perform these techniques. The use of HAVSMC allows a direct assessment of the crystal formation process in a living system albeit under controlled conditions. In a novel way, the ultrastructure as well as the morphology of the calcium phosphate deposits directly on the culture cell layer were characterised with physical techniques such as Field Effect Scanning Electron Microscopy, Energy Dispersive X-ray spectrometry and mFTIR spectroscopy. In summary, our data are excluding a physicochemical role of Mg2+ in inhibiting the crystal growth or in altering the calcium phosphate crystal composition or structure in an in vitro model of HAVSMC culture. Furthermore, the observed qualitative reduction of CPA spots should be linked to an active cellular role of Mg2+ in attenuating VC. Whether the in vitro data collected in the present study also have relevance in clinical setting is matter of additional works. The use of magnesium as a drug to lower serum calcium and phosphorus and its effect on outcomes in CKD patients was detailed in. To our knowledge, magnesium-containing phosphate binders have not yet been investigated for quantitative VC reduction in a controlled, prospective clinical setting. Likewise, supplemental in vitro investigations are currently ongoing and will further elucidate the cellular mechanisms by which Mg2+ is able to prevent VC. The potential for stem cell therapy to regenerate injured tissue has recently generated considerable interest. Two major problems facing stem cell heart therapy include low stem cell survival in vivo and negligible stem cell-to-target cell differentiation in vivo. The development of strategies to solve these problems should be facilitated by a better understanding of stem cell biology. One aspect of this biology that we believe will be particularly important to better understand is the regulation of energy metabolism because of its potential importance in differentiation and cell proliferation, important characteristics of stem cells. The concept that energy metabolism is involved in mediating cell proliferation was first introduced by Otto Warburg. His finding, referred to as the Warburg effect, was that highly proliferative cancer cells have high rates of glycolysis even under aerobic conditions. The survival and proliferation of these highly glycolytic cells correlate with high glycolysis rates. Increasing the coupling of glycolysis to glucose oxidation by treating cancer cells with dichloroacetate, a drug that increases pyruvate dehydrogenase activity by inhibiting pyruvate dehydrogenase kinase, not only increases glucose oxidation but also decreases glycolysis, decreases proliferation, and increases apoptosis. Genetically decreasing PDK expression also increases overall oxidative metabolism and decreases the proliferation of cancer cells. While not identical, embryonic stem cells and embryonal carcinoma cells have similar levels of metabolites, especially those involved in glycolysis. Therefore, cancer cell metabolism may provide a clue to the metabolism of stem cells. While there is relatively little evidence, the data do indicate that high glycolysis and low oxidative metabolism is important in stem cell survival and proliferation. Glycolysis is believed to be important in proliferation because it provides the cell with substrates needed to maintain high rates of macromolecular synthesis. For example, lipogenesis requires NADPH, which is produced by the pentose phosphate cycle that temporarily click here more help shunts substrates away from glycolysis. NADPH production and its use in lipogenesis appears to be essential for cancer cell proliferation. In addition, a key transcription factor regulating glycolysis, hypoxia inducible factor 1α, enhances macromolecular synthesis by increasing the protein expression of isocitrate dehydrogenase 2. IDH2 helps convert α ketoglutarate back to citrate which can be transported out of the mitochondria and used in lipogenesis. The concept that high glycolysis and low oxidative metabolism is necessary for proliferation and survival of proliferating cells is not completely straightforward.