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TRPC1 – a novel target to reduce human neointimal hyperplasia
Author(s) -
Sukumar Piruthivi,
Kumar Bhaskar,
Shah Samir,
Cheong Alex,
Xu Shang Zhong,
Munsch Christopher,
Porter Karen E,
Beech David J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb111
Subject(s) - trpc1 , medicine , neointimal hyperplasia , vascular smooth muscle , cardiology , hyperplasia , artery , intimal hyperplasia , myocardial infarction , pathology , smooth muscle , restenosis , receptor , transient receptor potential channel , stent
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 medical 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 homologue of Drosophila Transient Receptor Potential. Human vein samples obtained during coronary artery bypass graft surgery commonly exhibited an intimal structure containing smooth muscle cells which expressed more TRPC1 than the medial layer cells. Veins were organ‐cultured to allow growth of neo‐intimal 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, or proliferation of A7r5 smooth muscle cells in culture. The data suggest up‐regulated 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. Work supported by Wellcome Trust, British Heart Foundation and Nuffield Hospitals.