| Roles of matrix metalloproteinases in flow-induced outward vascular remodeling. | |
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MedLine Citation:
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PMID: 19513084 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sustained hemodynamic stresses, especially high blood flow, result in flow-induced outward vascular remodeling. Our previous study showed that macrophage depletion reduced flow-induced outward remodeling of the rat common carotid artery, indicating that macrophages are critical in flow-induced outward vascular remodeling. Macrophage is known to release proteinases, including matrix metalloproteinases (MMPs). Degradation and loosening of extracellular matrix by MMPs may facilitate vascular remodeling. Therefore, we assessed the functions of MMPs in flow-induced outward vascular remodeling by using the flow-augmented common carotid artery model in mice. We validated that ligation of the left common carotid artery increased blood flow and luminal diameter of the right common carotid artery without significant change in blood pressure of mice. To assess the functions of MMPs in flow-induced outward vascular remodeling, we used doxycycline (broad-spectrum MMP inhibitor), SB-3CT (selective MMP inhibitor), MMP-9 knockout mice, and MMP-12 knockout mice. Although there was only a trend for doxycycline treatment to reduce flow-induced outward vascular remodeling, SB-3CT treatment significantly reduced flow-induced outward vascular remodeling. In addition, flow-induced outward vascular remodeling was significantly reduced in MMP-9 knockout mice, but not in MMP-12 knockout mice. These data revealed that MMPs, especially MMP-9, are critical in flow-induced outward vascular remodeling. |
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Authors:
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Ryo Ota; Chie Kurihara; Tsung-Ling Tsou; William L Young; Yerem Yeghiazarians; Mayland Chang; Shahriar Mobashery; Atsuhiro Sakamoto; Tomoki Hashimoto |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-06-10 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 29 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-01 Completed Date: 2009-09-28 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1547-58 Citation Subset: IM |
Affiliation:
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Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94110, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / physiology Carotid Artery, Common* / anatomy & histology, metabolism Doxycycline / metabolism Hemodynamics* Male Matrix Metalloproteinase 12 / antagonists & inhibitors, genetics, metabolism* Matrix Metalloproteinase 9 / antagonists & inhibitors, genetics, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Physiologic / physiology* Rats Regional Blood Flow / physiology* Reproducibility of Results |
| Grant Support | |
ID/Acronym/Agency:
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P01 NS044155-06A15202/NS/NINDS NIH HHS; P01NS044155/NS/NINDS NIH HHS; R01 CA122417/CA/NCI NIH HHS; R01 CA122417-04/CA/NCI NIH HHS; R01 NS027713/NS/NINDS NIH HHS; R01 NS055876-01A1/NS/NINDS NIH HHS; R01 NS055876-02/NS/NINDS NIH HHS; R01 NS055876-03/NS/NINDS NIH HHS; R01NS055876/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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564-25-0/Doxycycline; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.4.24.65/Matrix Metalloproteinase 12 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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