Transcription profiles of aortic smooth muscle cells from atherosclerosis-prone and -resistant regions in young apolipoprotein E-deficient mice before plaque development.
OBJECTIVE
Site-specific atherosclerosis is generally attributed to differential gene expression in endothelial cells. We investigated whether the transcriptome of smooth muscle cells is different between atherosclerosis-prone and atherosclerosis-resistant regions in apolipoprotein E-deficient (apoE-/-) mice before plaque development, and in C57Bl/6 mice.


METHODS
De-endothelialized aortas (both strains: 3 males, 3 females, age 4 months) were divided into atherosclerosis-prone (AA: ascending aorta, aortic arch and proximal 2 mm of thoracic aorta) and -resistant (CTA: central thoracic aorta, i.e. 6 mm distal from the proximal 2 mm) regions. The transcriptome of these two regions was compared using whole-genome mouse microarrays.


RESULTS
Microarray analysis revealed differential expression (>2-fold difference) of 70 and 244 genes in C57Bl/6 and apoE-/- mice. This was confirmed for 6 genes using the real-time quantitative polymerase chain reaction. Up- or downregulation in the AA was observed for 33 and 37 genes in C57Bl/6, and for 186 and 58 genes in apoE-/- mice, respectively. The 201 genes that showed exclusively differential expression in apoE-/- mice were related to atherosclerotic processes, such as cell adhesion, proliferation, differentiation, motility, cell death, lipid metabolism and immune responses.


CONCLUSIONS
Our findings indicate that smooth muscle cells display an altered transcriptome at atherosclerosis-prone locations before actual lesion development.
Van Assche
Tim
T
Division of Pharmacology, Faculties of Medicine, University of Antwerp, Wilrijk, Belgium.
Hendrickx
Jan
J
Crauwels
Herta M
HM
Guns
Pieter-Jan
PJ
Martinet
Wim
W
Fransen
Paul
P
Raes
Martine
M
Bult
Hidde
H
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D006937:Hypercholesterolemia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology
D001057:Apolipoproteins E