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Mauban, J.H., Zacharia, J., Zhang, J., Wier, W.G. (2013) Vascular Tone and Ca2+ Signaling in Murine Cremaster Muscle Arterioles in Vivo. Microcirculation. Apr;20(3):269-77.
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Zhao, M., He, X., Bi, X.Y. Yu, X.J., Wier, W.G., Zang, W.J.. (2013) Vagal stimulation triggers peripheral vascular protection through the cholinergic anti-inflammatory pathway in a rat model of myocardial ischemia/reperfusion. Basic Res CardiolVol 108 Article No. 345
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He, X., Bi, X.Y., Lu, X.Z., Zhao, M., Yu, X.J., Sun, L., Xu, M., Wier, W.G., Zang W.J. Reduction of Mitochondria-Endoplasmic Reticulum Interactions by Acetylcholine Protects Human Umbilical Vein Endothelial Cells From Hypoxia/Reoxygenation Injury. Arterioscler Thromb Vasc Biol. 2015 Jul;35(7):1623-34. doi: 10.1161/ATVBAHA.115.305469. Epub 2015 May 14.
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We are using high resolution imaging to study the role of Ca2+ in adrenergic control mechanisms in intact, pressurized resistance arteries. Imaging Ca2+ in such a preparation is challenging, compared to single isolated cells. It is expected to be highly rewarding however, because of the ability to see [Ca2+]i during truly physiological stimuli, such as pressure, shear stress, or neuronal stimulation. Furthermore, the cells are connected normally (via gap junctions), allowing the observation of cellular communication or co-ordinated activity that cannot exist in isolated cells. This is most important in view of the emerging concept that arterial function is carried out by 'information networks within the arterial wall' (Beny, 1999). While the potential benefits of such preparations are undeniable, the difficulty in imaging Ca2+ in such preparations is that they are thick, scatter light and can move. Nevertheless, our preliminary data shows that with modern optical sectioning techniques (confocal and two-photon) it is possible to observe events within subcellular volumes within part of a much larger scene, comprised of a group of inter-connected cells. In the case of an artery, such a scene can encompass several vascular smooth muscle cells, nerve endings and endothelial cells. Recently, we have been concerned with the mechanisms governing release of the sympathetic neurotransmitters, NE and ATP from sympathetic nerve endings in these arteries. ATP binds to P2X1 receptors to activate inward Ca2+ current and produce a local, non-propagating post-junctional Ca2+ transient that we called a 'jCaT' (junctional Ca Transient). NE binds to a1-adrenoceptors to produce propagating Ca2+ waves. These studies are providing a new picture of Ca2+ signaling in the smooth muscle of arteries. In summary, by obtaining high resolution images of molecular messengers within the walls of intact pressurized arteries, it is hoped that a new, more integrated view of the cellular and inter-cellular mechanisms that control vascular resistance can be obtained.
1R01HL122827 0401/2016 - 03/31/2020. "Creation of Optical Biosensor Mice for Longitudinal Studies of Vascular Function". MPI grant with Mark Rizzo.