RGD Reference Report - Hyperlipidaemia impairs the circadian clock and physiological homeostasis of vascular smooth muscle cells via the suppression of Smarcd1. - Rat Genome Database

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Hyperlipidaemia impairs the circadian clock and physiological homeostasis of vascular smooth muscle cells via the suppression of Smarcd1.

Authors: Chen, S  Ding, Y  Zhang, Z  Wang, H  Liu, C 
Citation: Chen S, etal., J Pathol. 2014 Jun;233(2):159-69. doi: 10.1002/path.4338. Epub 2014 Mar 28.
RGD ID: 9586357
Pubmed: PMID:24615205   (View Abstract at PubMed)
DOI: DOI:10.1002/path.4338   (Journal Full-text)

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 bmal1, through co-activation of the nuclear orphan receptor RORalpha in VSMCs. The co-activation of Smarcd1 and RORalpha is dependent on the mediation of PGC-1alpha, 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SMARCD1Humanfamilial hyperlipidemia  ISOSmarcd1 (Rattus norvegicus)mRNA:decreased expression:thoracic aortaRGD 
Smarcd1Ratfamilial hyperlipidemia  IEP mRNA:decreased expression:thoracic aortaRGD 
Smarcd1Mousefamilial hyperlipidemia  ISOSmarcd1 (Rattus norvegicus)mRNA:decreased expression:thoracic aortaRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Smarcd1Ratcellular response to fatty acid  IEP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Smarcd1Ratchromatin binding  IDA  RGD 
RoraRatprotein binding  IPISmarcd1 (Rattus norvegicus) RGD 
Smarcd1Ratsignaling receptor binding  IPIRora (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rora  (RAR-related orphan receptor A)
Smarcd1  (SWI/SNF related BAF chromatin remodeling complex subunit D1)

Genes (Mus musculus)
Smarcd1  (SWI/SNF related BAF chromatin remodeling complex subunit D1)

Genes (Homo sapiens)
SMARCD1  (SWI/SNF related BAF chromatin remodeling complex subunit D1)


Additional Information