Accelerated arterial stiffening and gene expression profile of the aorta in patients with coronary artery disease.
BACKGROUND
Hypertension and chronic renal failure (CRF) are considered models of accelerated arterial stiffening. Arterial stiffness increases further when CRF is associated with hypertension. We hypothesized that, in patients with mild CRF, aortic gene expression profile would include genes involved in arterial calcifications and enlargement.


METHODS
We analysed human aorta with the 'GeneChip Microarray' technology, in patients with or without CRF, scheduled for a coronary artery bypass graft.


RESULTS
Nine of 25 patients had high-quality RNA and were included in the study. Among the 101 transcripts differentially expressed between CRF patients and controls, 97 transcripts were overexpressed in CRF patients. Two genes had the highest overexpression in CRF patients: lumican (LUM), involved in the regulation of collagen fibrillogenesis; and ornithine decarboxylase (ODC1), involved in polyamine biosynthesis, smooth muscle cell growth and proliferation. Immunohistochemical staining revealed an increased amount of LUM and ODC1 in the vascular smooth muscle cells (VSMCs) of CRF compared to non-CRF aortic sections. Eight genes were implicated in the regulation of the cytoskeleton (including capping protein muscle Z-line 1 alpha and moesin) and cell migration, and five genes were implicated in extracellular matrix function and apoptosis. A trend towards an upregulation of candidate genes involved in arterial calcifications was observed in CRF patients, but did not reach statistical significance. Carotid-femoral pulse wave velocity was not correlated with gene expression level.


CONCLUSIONS
In conclusion, these results show that patients at an early stage of CRF have a specific gene expression profile of aortic tissue and suggest that genes implicated in collagen fibrillogenesis, and VSMCs migration and proliferation, particularly LUM and ODC1, may play a role.
Fassot
Céline
C
Faculty of Medicine, University Paris-Descartes, Department of Pharmacology, Georges Pompidou European Hospital, Paris, France.
Briet
Marie
M
Rostagno
Philippe
P
Barbry
Pascal
P
Perret
Claudine
C
Laude
Dominique
D
Boutouyrie
Pierre
P
Bozec
Erwan
E
Bruneval
Patrick
P
Latremouille
Christian
C
Laurent
Stéphane
S
D000328:Adult; D001011:Aorta / Q000502:physiology*; D001018:Aortic Diseases / Q000235:genetics / Q000503:physiopathology; D002114:Calcinosis / Q000235:genetics / Q000503:physiopathology; D002339:Carotid Arteries / Q000502:physiology; D003324:Coronary Artery Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011673:Pulsatile Flow / Q000235:genetics