Contribution of the Potassium Channels K(V)1.3 and K(Ca)3.1 to Smooth Muscle Cell Proliferation in Growing Collateral Arteries

Lasch, Manuel; Martinez, Amelia Caballero; Kumaraswami, Konda; Ishikawa-Ankerhold, Hellen; Meister, Sarah und Deindl, Elisabeth (2020): Contribution of the Potassium Channels K(V)1.3 and K(Ca)3.1 to Smooth Muscle Cell Proliferation in Growing Collateral Arteries. In: Cells, Bd. 9, Nr. 4, 913

Abstract

Collateral artery growth (arteriogenesis) involves the proliferation of vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Whereas the proliferation of ECs is directly related to shear stress, the driving force for arteriogenesis, little is known about the mechanisms of SMC proliferation. Here we investigated the functional relevance of the potassium channels K(V)1.3 and K(Ca)3.1 for SMC proliferation in arteriogenesis. Employing a murine hindlimb model of arteriogenesis, we found that blocking K(V)1.3 with PAP-1 or K(Ca)3.1. with TRAM-34, both interfered with reperfusion recovery after femoral artery ligation as shown by Laser-Doppler Imaging. However, only treatment with PAP-1 resulted in a reduced SMC proliferation. qRT-PCR results revealed an impaired downregulation of alpha smooth muscle-actin (alpha SM-actin) and a repressed expression of fibroblast growth factor receptor 1 (Fgfr1) and platelet derived growth factor receptor b (Pdgfrb) in growing collaterals in vivo and in primary murine arterial SMCs in vitro under K(V)1.3. blockade, but not when K(Ca)3.1 was blocked. Moreover, treatment with PAP-1 impaired the mRNA expression of the cell cycle regulator early growth response-1 (Egr1) in vivo and in vitro. Together, these data indicate that K(V)1.3 but not K(Ca)3.1 contributes to SMC proliferation in arteriogenesis.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch