David X. Zhang, PhD
Associate Professor
Locations
- Pharmacology and Toxicology
Contact Information
General Interests
Education
Research Interests
The overall emphasis of our laboratory is to understand signaling mechanisms in regulation of blood vessel reactivity and homeostasis under normal states as well as in diseases such as coronary artery disease (CAD), hypertension, and diabetes.
This regulation involves two major cell types in the vessel wall, namely the endothelial and smooth muscle cells. The endothelium is a single layer of cells lining the lumen of blood vessels. It regulates vascular tone and homeostasis through the release of various vasoactive factors. In response to either mechanical (e.g., flow or shear stress) or chemical (e.g., receptor agonists) cues, the endothelium synthesizes and releases nitric oxide (NO), prostacyclin (PGI2), and less well-understood endothelium-derived hyperpolarizing (EDH) factors such as metabolites of arachidonic acid and hydrogen peroxide (H2O2). These endothelial factors can diffuse out of the endothelial layer into the medial layer of the vessel wall and in turn regulate many functions of smooth muscle cells, including smooth muscle resting tone, relaxation and contraction response, and cell proliferation. In human coronary arterioles, H2O2 serves as a key flow-elicited vasodilator factor in the presence of CAD whereas other traditional factors (NO and PGI2) play a more significant role in vasodilation in the absence of CAD or its risk factors. Although both H2O2 and NO dilate coronary arterioles, each mediator has different or opposing non-vasomotor effects on vascular homeostasis and propensity for atherosclerosis. It remains largely unsolved how flow elicits two distinct classes of vasodilators in subjects with CAD versus those without. In addition, whether and how vascular smooth muscle of the human microcirculation changes function during CAD and other diseases remains poorly understood.
The current research is focused on the role of transient receptor potential (TRP) channels, a newly recognized family of calcium-permeable cation channels expressed in vascular endothelial cells, in mediating the conversion of vasodilator factors (NO/PGI2 in health and H2O2 in disease) in human coronary microcirculation. A second line of research relates to the function of smooth muscle K+ channels, such as Ca2+-activated K+ (KCa) and voltage-gated K+ (KV) channels, in arterioles from subjects with and without CAD. These smooth muscle K+ channels are the key end-effector of vasomotor control in the microcirculation. The studies are biomedically significant because they involve the use of human tissue in addition to animal models. Studies are performed with an integrated approach ranging from cellular and molecular techniques (Ca2+ imaging, protein mutagenesis), electrophysiology (patch clamping), to isolated vessel reactivity and in vivo vascular function assays.
Publications
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(Kosuru R, Romito O, Sharma GP, Ferraresso F, Ghadrdoost Nakhchi B, Yang K, Mammoto T, Mammoto A, Kastrup CJ, Zhang DX, Goldspink PH, Trebak M, Chrzanowska M.) Arterioscler Thromb Vasc Biol. 2024 Nov;44(11):2271-2287 PMID: 39324266 PMCID: PMC11495542 SCOPUS ID: 2-s2.0-85206451357 09/26/2024
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(Nadezhdin KD, Talyzina IA, Parthasarathy A, Neuberger A, Zhang DX, Sobolevsky AI.) Nat Commun. 2023 Jun 23;14(1):3733 PMID: 37353478 PMCID: PMC10290124 SCOPUS ID: 2-s2.0-85162777271 06/24/2023
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(Sylvester AL, Zhang DX, Ran S, Zinkevich NS.) Biomolecules. 2022 Jun 13;12(6) PMID: 35740948 PMCID: PMC9221095 SCOPUS ID: 2-s2.0-85131782032 06/25/2022
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(Xie Y, Nishijima Y, Zinkevich NS, Korishettar A, Fang J, Mathison AJ, Zimmermann MT, Wilcox DA, Gutterman DD, Shen Y, Zhang DX.) Basic Res Cardiol. 2022 Apr 25;117(1):24 PMID: 35469044 PMCID: PMC9119129 SCOPUS ID: 2-s2.0-85128849246 04/27/2022
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(Nishijima Y, Hader SN, Hanson AJ, Zhang DX, Sparapani R, Gutterman DD, Beyer AM.) Cardiovasc Res. 2022 Jan 07;118(1):18-19 PMID: 34755839 PMCID: PMC8689948 SCOPUS ID: 2-s2.0-85123651313 11/11/2021
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(Singh B, Kosuru R, Lakshmikanthan S, Sorci-Thomas MG, Zhang DX, Sparapani R, Vasquez-Vivar J, Chrzanowska M.) Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):638-650 PMID: 33267664 PMCID: PMC8105264 SCOPUS ID: 2-s2.0-85104181830 12/04/2020
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(Korishettar AM, Nishijima Y, Wang Z, Xie Y, Fang J, Wilcox DA, Zhang DX.) Br J Pharmacol. 2021 Feb;178(3):709-725 PMID: 33184836 PMCID: PMC9121782 SCOPUS ID: 2-s2.0-85098221966 11/14/2020
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(Kosuru R, Singh B, Lakshmikanthan S, Nishijima Y, Vasquez-Vivar J, Zhang DX, Chrzanowska M.) Front Cell Dev Biol. 2021;9:741935 PMID: 34422844 PMCID: PMC8378398 08/24/2021
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(Kosuru R, Singh B, Lakshmikanthan S, Nishijima Y, Vasquez-Vivar J, Zhang DX, Chrzanowska M.) Front Cell Dev Biol. 2021;9:687598 PMID: 34222255 PMCID: PMC8247587 07/06/2021
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(Zhang DX, Gutterman DD.) Arterioscler Thromb Vasc Biol. 2019 Dec;39(12):2454-2456 PMID: 31770031 PMCID: PMC6980742 SCOPUS ID: 2-s2.0-85075688768 11/27/2019
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(Sharma S, Goswami R, Zhang DX, Rahaman SO.) J Cell Mol Med. 2019 Feb;23(2):761-774 PMID: 30450767 PMCID: PMC6349341 SCOPUS ID: 2-s2.0-85056765656 11/20/2018
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(Palygin O, Miller BS, Nishijima Y, Zhang DX, Staruschenko A, Sorokin A.) FASEB J. 2019 Feb;33(2):2636-2645 PMID: 30303741 PMCID: PMC6338658 SCOPUS ID: 2-s2.0-85061064863 10/12/2018