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Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia
- Source :
- Circulation Research. 98:557-563
- Publication Year :
- 2006
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2006.
-
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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Swine
Physiology
medicine.medical_treatment
neointimal hyperplasia
Rats, Inbred WKY
Muscle, Smooth, Vascular
Article
Mice
Angioplasty
medicine
Animals
Humans
Saphenous Vein
Vascular Diseases
Myocardial infarction
Vein
Cells, Cultured
Cell Proliferation
TRPC Cation Channels
Neointimal hyperplasia
Hyperplasia
business.industry
Anatomy
Calcium Channel Blockers
medicine.disease
Tunica intima
Rats
Up-Regulation
Mice, Inbred C57BL
medicine.anatomical_structure
transient receptor potential
Circulatory system
calcium channel
Calcium
vascular smooth muscle cell
Tunica Intima
Cardiology and Cardiovascular Medicine
business
Artery
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....92d9649ebce63a52efea0135bf7ea91c