This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Breemen, C. Articles by Okon, E. B. Search for Related Content PubMed PubMed Citation Articles by van Breemen, C. Articles by Okon, E. B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Medline Plus Health Information Vascular Diseases Related Collections Related Article

(Circulation Research. 2006;98:446.)
© 2006 American Heart Association, Inc.

Editorials

TRP Proteins

A New Dimension in the Treatment of Occlusive Vascular Disease

Cornelis van Breemen, Damon Poburko, Elena B. Okon

From the Department of Anesthesiology, Pharmacology, and Therapeutics, The Child and Family Research Institute and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia.

Correspondence to Cornelis (Casey) van Breemen, DVM, PhD, Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Medical Sci Block C, 2176 Health Sciences Mall V6T 1Z3. E-mail breemen@interchange.ubc.ca

See related article, pages 557–563

Key Words: smooth muscle cells • calcium channels • neointima • restenosis • atherosclerosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Circulation Research, Beech and collaborators report their exciting discovery that blockade of the TRPC1 channel inhibits the salient features of vascular disease: smooth muscle cell proliferation and neointima formation.¹ The idea of using Ca²⁺ channel blockers as therapy for vascular disease was introduced in the late seventies and led to a large body of literature.^2,3 Calcium antagonists originally were introduced as antiischemic and antihypertensive drugs, but were also found to reduce the development of intimal lesions in many animal models of atherosclerosis.^4,5 After injury caused by angioplasty or venous coronary bypass grafting, occlusive vascular diseases such as atherosclerosis, neointimal hyperplasia, and restenosis stem from an adaptive reaction of the blood vessels to local injury and altered conditions of blood flow, which involves a shift of smooth muscle cells from contractile to synthetic phenotype characterized by activation of smooth muscle cell proliferation and migration.⁶ These processes involve various proliferation signal cascades such as Akt, MAPK, and cadherin/ß-catenin.^7,8,9 There is substantial support for a central regulatory role of intracellular Ca²⁺ in these processes,^10,11 and many publications support the effectiveness of calcium antagonists in reducing smooth muscle proliferation.^12,13

However, the term "calcium antagonist" refers exclusively to blockers of L-type voltage gated Ca²⁺ channels (VGCC), and 3 decades of experience with these agents have led to limited success in easing the ravages of occlusive vascular disease. This disappointment appears to be related to 3 relevant characteristics of calcium antagonists. First, in the vasculature their primary target is the VGCC . . . [Full Text of this Article]

Related Article:

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

B. Kumar, K. Dreja, S.S. Shah, A. Cheong, S.-Z. Xu, P. Sukumar, J. Naylor, A. Forte, M. Cipollaro, D. McHugh, P.A. Kingston, A.M. Heagerty, C.M. Munsch, A. Bergdahl, A. Hultgårdh-Nilsson, M.F. Gomez, K.E. Porter, P. Hellstrand, and D.J. Beech
Circ. Res. 2006 98: 557-563. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF]