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Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia.

Kumar, B ; Dreja, Karl LU ; Shah, S ; Cheong, A ; Xu, S-Z ; Sukumar, P ; Naylor, J ; Forte, A ; Cipollaro, M and McHugh, D , et al. (2006) In Circulation Research 98(4). p.557-563
Abstract
Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after... (More)
Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure. (Less)
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published
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keywords
neointimal hyperplasia, transient receptor potential, calcium channel, vascular smooth muscle cells
in
Circulation Research
volume
98
issue
4
pages
557 - 563
publisher
American Heart Association
external identifiers
  • scopus:33645280662
  • pmid:16439693
  • wos:000235728300021
  • pmid:16439693
ISSN
0009-7330
DOI
10.1161/01.RES.0000204724.29685.db
language
English
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yes
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99167f2e-3a1f-4872-b140-c0182f09c521 (old id 1137408)
date added to LUP
2016-04-01 15:25:03
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2020-01-12 18:28:15
@article{99167f2e-3a1f-4872-b140-c0182f09c521,
  abstract     = {Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.},
  author       = {Kumar, B and Dreja, Karl and Shah, S and Cheong, A and Xu, S-Z and Sukumar, P and Naylor, J and Forte, A and Cipollaro, M and McHugh, D and Kingston, P A and Heagerty, A M and Munsch, C M and Bergdahl, Andreas and Hultgårdh, Anna and Gomez, Maria and Porter, K E and Hellstrand, Per and Beech, D J},
  issn         = {0009-7330},
  language     = {eng},
  number       = {4},
  pages        = {557--563},
  publisher    = {American Heart Association},
  series       = {Circulation Research},
  title        = {Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia.},
  url          = {http://dx.doi.org/10.1161/01.RES.0000204724.29685.db},
  doi          = {10.1161/01.RES.0000204724.29685.db},
  volume       = {98},
  year         = {2006},
}