Skip to main content
main-content

01.12.2014 | ORIGINAL ARTICLE | Ausgabe 6/2014

Cardiovascular Drugs and Therapy 6/2014

K+ Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation

Zeitschrift:
Cardiovascular Drugs and Therapy > Ausgabe 6/2014
Autoren:
P. Cidad, L. Novensà, M. Garabito, M. Batlle, A. P. Dantas, M. Heras, J. R. López-López, M. T. Pérez-García, M. Roqué
Wichtige Hinweise
P. Cidad and L. Novensà contributed equally to the study.
An erratum to this article can be found at http://​dx.​doi.​org/​10.​1007/​s10557-015-6578-5.

Abstract

Introduction

K+ channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures.

Purpose

To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion .

Methods

Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K+ channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro.

Results

Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4 % vs. 70 ± 5 % in BPN, p < 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6 % vs. 58 ± 20 % with vehicle, p < 0.05).

Conclusions

Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 6/2014

Cardiovascular Drugs and Therapy 6/2014 Zur Ausgabe
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Kardiologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Kardiologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise