Role of the intermediate-conductance Ca²⁺-activated K⁺ channel (K[ca]3.1) in coronary smooth muscle cell phenotypic modulation

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Smooth muscle cell phenotypic modulation is characterized by suppression of smooth muscle specific marker gene expression, migration, and proliferation which occurs during the development of atherosclerosis and post-angioplasty restenosis. Our objective was to determine the role of the intermediate-conductance calcium-activated potassium channel (KCa3.1) in coronary smooth muscle cell phenotypic modulation in vitro by growth factor stimulation and in vivo using swine models of early atherosclerosis and post-angioplasty restenosis. Our data demonstrate that KCa3.1 is required for growth factor- and angioplasty-induced smooth muscle cell phenotypic modulation, and plays a similar role during early coronary atherosclerosis. Furthermore, blockade of KCa3.1 prevents smooth muscle cell phenotypic modulation, and limits subsequent restenosis. In conclusion, blockade of KCa3.1 could prove to be an important therapeutic strategy for limiting post-angioplasty restenosis, as well as the progression of coronary artery disease.