Less REST, more vascular disease? Regulation of cell cycle and migration of vascular smooth muscle cells

Abstract

Neointimal hyperplasia and atherosclerosis are cardiovascular abnormalities resulting in heart attacks and strokes--major causes of death and disability in societies with a western-style diet. Both are contributed to significantly by a phase of enhanced cell cycle activity and migration of vascular smooth muscle cells. Here we describe how this activity is associated with a switch in the types of ion channel controlling trans-membrane ion transport. In particular we stress the de novo expression of the K(Ca)3.1 potassium channel when the cells proliferate, but we also review evidence of changes in other ion channels. The molecular mechanisms governing such switches in ion transport have been unknown until we recently showed downregulation of the repressive REST transcription factor is an important step. Here we explain and expand the hypothesis that REST-regulation of ion transport has a previously unrecognised role in cell proliferation.