| Mechanosensitive transient receptor potential vanilloid type 1 channels contribute to vascular remodeling of rat fistula veins. | |
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MedLine Citation:
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PMID: 20638226 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: We previously showed that matrix metalloproteinases (MMPs) contribute to tremendous blood flow-induced venous wall thickening during the maturation of an arteriovenous fistula (AVF). However, how veins in the fistula sense a dramatic change in the blood flow remains unknown. Because mechanosensitive transient receptor potential vanilloid channels (TRPVs) are present in the endothelium, we examined whether the Ca2+-permeable TRPVs play a role in remodeling of fistula veins. METHODS: The fistula veins were generated at femoral AVF of Wistar rats. Changes in the hemodynamics and the width and internal radius of the iliac vein were studied at 3, 7, 14, and 28 days, then the iliac vein was removed and examined for changes in wall thickness and protein or mRNA expression by immunofluorecent stain, Western blot, or real time PCR. Changes in MMP2 activity was examined by gelatin zymography. Two ligatures were performed in iliac vein to prevent venodilatation to confirm the effect of dramatic changes in hemodynamics on TRPV expression. The specific role of TRPV was studied in another group of fistula veins given with capsazepine via a subcutaneous mini-osmotic pump for 28 days. RESULTS: The fistula veins demonstrated high flow/wall shear stress (WSS), wall thickening, and venodilatation compared with control veins. The WSS increase was positively correlated with upregulation of TRPV1, but not TRPV4. Narrowing fistula veins prevented TRPV1 upregulation, indicating that high flow directly upregulates TRPV1. We examined the underlying signaling components and found that enhanced Ca2+/calmodulin-dependent protein kinase II (CaMK II) activity upregulated endothelial nitric oxide synthase (eNOS) and downregulated arginase I in the fistula veins. These changes were reversed by a CaMK II inhibitor. The relative levels of eNOS and arginase I activity consequently augmented NO formation, which coincided with an increase in MMP2 activity. Chronic inhibition of TRPV1 in the fistula veins by capsazepine showed no effect on high flow and TRPV1 expression, but markedly attenuated WSS, which was concomitantly associated with attenuation of CaMK II activity, NO-dependent MMP2 activation, and remodeling. CONCLUSION: These findings indicate that TRPV1 is essential in the remodeling of AVFs and that WSS leads to TRPV1 upregulation, which then enhances remodeling, therefore, inhibition of TRPV1 pathway may prolong the lifespan of an AVF by decreasing WSS and vein wall remodeling. |
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Authors:
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Yih-Sharng Chen; Ming-Jen Lu; Ho-Shiang Huang; Ming-Chieh Ma |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-17 |
Journal Detail:
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Title: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter Volume: 52 ISSN: 1097-6809 ISO Abbreviation: J. Vasc. Surg. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-05 Completed Date: 2010-12-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8407742 Medline TA: J Vasc Surg Country: United States |
Other Details:
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Languages: eng Pagination: 1310-20 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved. |
Affiliation:
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Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei, Taiwan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arginase / metabolism Arteriovenous Shunt, Surgical* Benzylamines / administration & dosage Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors, metabolism Capsaicin / administration & dosage, analogs & derivatives Female Femoral Artery / surgery Femoral Vein / drug effects, metabolism*, pathology, physiopathology, surgery Hemodynamics Iliac Vein / drug effects, metabolism*, pathology, physiopathology, surgery Infusion Pumps, Implantable Infusions, Intravenous Ligation Matrix Metalloproteinase 2 / metabolism Mechanotransduction, Cellular* / drug effects Nitric Oxide / metabolism Nitric Oxide Synthase Type III / metabolism Protein Kinase Inhibitors / administration & dosage RNA, Messenger / metabolism Rats Rats, Wistar Sensory System Agents / administration & dosage Sulfonamides / administration & dosage TRPV Cation Channels / antagonists & inhibitors, genetics, metabolism* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Benzylamines; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Sensory System Agents; 0/Sulfonamides; 0/TRPV Cation Channels; 0/Trpv1 protein, rat; 0/capsazepine; 10102-43-9/Nitric Oxide; 139298-40-1/KN 93; 404-86-4/Capsaicin; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinase Type 2; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.24/Mmp2 protein, rat; EC 3.5.3.1/Arginase; EC 3.5.3.1/arginase I, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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