By Roger J. Laham, Donald S. Baim
An interdisciplinary panel of pioneers and opinion leaders assessment the elemental, preclinical, scientific, and developmental pathways to new remedy techniques, equivalent to healing angiogenesis and myogenesis. The authors benefit from new organic figuring out, novel healing objectives, a number of on hand and well-studied healing techniques, and the mandatory imaging suggestions to degree results. Their in-depth discussions disguise the id of recent healing pursuits and pathways, the research of transcriptional components, grasp swap molecules, cell-based methods, chemokines, a greater figuring out of the consequences of getting older, endothelial disorder, and hypercholesterolemia in accordance with angiogenic stimuli. Highlights contain exam of drug supply difficulties, results degree, stem treatment, high-risk interventions, improvement pathways, and destiny chances.
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Targeted disruption of this factor led to abnormalities in angiogenesis that could be rescued by administration of AP-1 (53). Another transcription factor that also appears to regulate AP1 levels is the nuclear receptor COUP-TFII (54). Targeted disruption of this gene is associated with angiogenic defects and marked reductions in the level of AP-1. The differentiation of mesechymal cells into vascular smooth muscle cells is also a highly orchestrated process. Members of the MADS-box factors such as SMAD5 and MEF2C mediate the effects of TGF-β, thereby promoting endothelial mesenchymal interactions and smooth muscle cell differentiation.
One of the earliest transcription factors required for the differentiation of a pluripotent stem cell into a hemangioblast is SCL/tal-1 (50). Knockout studies suggest that two transcription factors that may be required for differentiation or survival of endothelial cells early in development are Fra1 and Vezf1 (27,35). Another early step in the differentiation of endothelial cells is the expression of VEGF receptors that promote not only the Fig 1. The role of transcription factors during different stages of vascular development.
An ideal animal model for angiogenesis studies should have the following characteristics (1): 1. 2. 3. 4. Small, yet easily implemented and maintained Coronary anatomy and innate collateral circulation similar to humans Collateral development in the virtual absence of infarction Consistent, regional abnormalities in left-ventricular (LV) perfusion and function 5. Easily assessed in response to simple interventions Although this optimal model may not always be attainable, models should strive to reflect the “ideal” based on the above criteria and following the basic knowledge of anatomy, physiology, and function (Table 1).
Angiogenesis and Direct Myocardial Revascularization (Contemporary Cardiology) by Roger J. Laham, Donald S. Baim