Intermediate Conductance Calcium-Activated Potassium Channel Activation in Stem Cell Antigen-1 Positive Cells Contributed to Vascular Restenosis.

Abstract

BACKGROUND: Vascular restenosis, a common complication following vascular reconstruction, results in stenosis or blockage that impairs vascular remodeling. This process is driven by the activation of vascular stem cells. Growing evidence suggests that intermediate conductance calcium-activated potassium (IK) channels play a crucial role in regulating the function of these cells. This study aims to explore how IKchannels influence Sca-1(stem cell antigen-1 positive) stem cells in the context of vascular anastomotic restenosis. METHODS: To investigate the role and mechanism of the IKchannel in Sca-1cell activation and its involvement in vascular anastomosis restenosis, we assessed the impact of IKchannel deficiency on the vascular restenosis-promoting ability of Sca-1cells using a mouse femoral artery anastomosis model. Mechanistic insights were gained through patch-clamp electrophysiology, intracellular Cameasurement, and molecular biology techniques. RESULTS: Genetic deletion of IKchannels in IKmice led to reduced neointimal formation and decreased proliferation of Sca-1cells at the anastomotic site. In vitro studies confirmed the presence of functional IKchannels in Sca-1cells and demonstrated that IKand TRPC1 (transient receptor potential canonical 1) channels cooperate in regulating membrane potential and intracellular Calevels. Furthermore, our findings suggest that IKchannel-mediated modulation of ERK (extracellular signal-regulated kinase) and p38 phosphorylation underpins a key signaling mechanism in this process. CONCLUSIONS: This study clarifies the role of the IK-TRPC1-Capathway in activating vascular Sca-1cells and establishes the contribution of the IKchannel to vascular restenosis development. Understanding how IKchannels affect the function of vascular Sca-1cells provides valuable insights into the complex mechanisms of vascular remodeling during vascular stenosis.