Hyperlipidaemia impairs the circadian clock and physiological homeostasis of vascular smooth muscle cells via the suppression of Smarcd1. Issue 2 (28th March 2014)

• Record Type: Journal Article
• Authors: Chen, Siyu; Ding, Yan; Zhang, Zhao; Wang, Han; Liu, Chang
• Is Part Of: Journal of pathology. Volume 233:Issue 2(2014)
• Page Start: 159
• Page End: 169
• Publication Date: 2014-03-28
• Subjects: Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.4338
• Languages: English
• ISSNs: 0022-3417

Abstract

<abstract abstract-type="main" id="path4338-abs-0001"> <title>Abstract</title> <p id="path4338-para-0001">Many mammalian physiological processes show diurnal oscillation and are controlled by a circadian clock. Disruption of the circadian clock has been implicated in the pathogenesis of cardiovascular disorders, but the mechanism through which clock and vessel function are integrated is unclear. Here we show that the rhythmicity of key clock genes and Smarcd1, a member of the SWI/SNF chromatin remodelling complex family, is suppressed in the layer of vascular smooth muscle cells (VSMCs) of the thoracic aorta of hyperlipidaemic rats fed a high‐fat diet (HFD). Smarcd1 stimulates the transcription of clock genes, notably <italic>bmal1</italic>, through co‐activation of the nuclear orphan receptor ROR<italic>α</italic> in VSMCs. The co‐activation of Smarcd1 and ROR<italic>α</italic> is dependent on the mediation of PGC‐1<italic>α</italic>, a transcriptional co‐activator. Pathophysiologically, Smarcd1 inhibits VSMC proliferation and migration by blocking cell cycle re‐entry and via the activation of kinase signalling pathways. Our results demonstrate that Smarcd1 is a critical node integrating the circadian clock and VSMC physiological homeostasis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.</p> </abstract>