gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

Pharmacological inhibition of IKCa1 K+-channels as a new therapeutic strategy to prevent neointima formation following balloon catheter injury

Pharmakologische Inhibition von IKCa1 K+-Kanäle als neue Therapiestrategie zur Unterdrückung der Neointimaproliferation nach Ballonkatheterdilatation

Meeting Abstract

  • J. Hoyer - Philipps-Universität Marburg (Marburg, D)
  • C. Busch - Philipps-Universität Marburg (Marburg, D)
  • I. Grgic - Philipps-Universität Marburg (Marburg, D)
  • M. Tysiak - Philipps-Universität Marburg (Marburg, D)
  • R. Köhler - Philipps-Universität Marburg (Marburg, D)
  • T. Maier - Philipps-Universität Marburg (Marburg, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP129

The electronic version of this article is the complete one and can be found online at:

Published: August 8, 2006

© 2006 Hoyer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Balloon catheterization stimulates proliferation and migration of vascular smooth muscle cells (VSMC) leading to neointimal thickening and vascular restenosis. In a rat model of balloon catheter injury (BCI) we investigated whether alterations in expression of Ca2+ activated K+ channels (KCa) are involved in intimal hyperplasia. Mature medial VSMC exclusively expressed large-conductance KCa (BKCa) channels. Two weeks after BCI, expression of BKCa was significantly reduced in neointimal VSMC, while expression of intermediate-conductance KCa (IKCa1) channels was significantly augmented. Using the aortic VSMC cell line A7r5 we ascertained that IKCa1 up-regulation occurred via EGF- or PDGF-mediated activation of the MEK/ERK pathway while down-regulation of BKCa did not depend on this pathway. Mitogen-induced VSMC proliferation in vitro was suppressed by the selective IKCa1 blocker TRAM-34, SiRNA-mediated knockdown of IKCa1, but not by TRAM-7, an inactive analogue of TRAM-34, or by the BKCa blocker iberiotoxin. Daily in vivo administration of TRAM-34 or clotrimazole (each 120 mg/kg) to rats significantly reduced intimal hyperplasia by ~50% after BCI. Reduction of intimal hyperplasia was accompanied by decreased neointimal cell content. The switch towards IKCa1 expression may promote excessive neointimal VSMC proliferation and blockade of IKCa1 could therefore represent a new therapeutic strategy to prevent restenosis after angioplasty. IKCa1 blocker may also be usefull for the treatment of cardiovascular diseases characterized by abnormal VSMC proliferation or vascular remodelling as a consequence of hypertension.