Transcriptional alterations in the left ventricle of three hypertensive rat models.
Left ventricular hypertrophy (LVH) is commonly associated with hypertension and represents an independent cardiovascular risk factor. The aim of this study was to test the hypothesis that the cardiac overload related to hypertension is associated to a specific gene expression pattern independently of genetic background. Gene expression levels were obtained with microarrays for 15,866 transcripts from RNA of left ventricles from 12-wk-old rats of three hypertensive models [spontaneously hypertensive rat (SHR), Lyon hypertensive rat (LH), and heterozygous TGR(mRen2)27 rat] and their respective controls. More than 60% of the detected transcripts displayed significant changes between the three groups of normotensive rats, showing large interstrain variability. Expression data were analyzed with respect to hypertension, LVH, and chromosomal distribution. Only four genes had significantly modified expression in the three hypertensive models among which a single gene, coding for sialyltransferase 7A, was consistently overexpressed. Correlation analysis between expression data and left ventricular mass index (LVMI) over all rats identified a larger set of genes whose expression was continuously related with LVMI, including known genes associated with cardiac remodeling. Positioning the detected transcripts along the chromosomes pointed out high-density regions mostly located within blood pressure and cardiac mass quantitative trait loci. Although our study could not detect a unique reprogramming of cardiac cells involving specific genes at early stage of LVH, it allowed the identification of some genes associated with LVH regardless of genetic background. This study thus provides a set of potentially important genes contained within restricted chromosomal regions involved in cardiovascular diseases.
Cerutti
Catherine
C
Equipe d'Accueil 3740 Génomique fonctionnelle dans l'athérothrombose, Université Lyon 1, Lyon, France. cerutti@univ-lyon1.fr
Kurdi
Mazen
M
Bricca
Giampiero
G
Hodroj
Wassim
W
Paultre
Christian
C
Randon
Jacques
J
Gustin
Marie-Paule
MP
D000818:Animals; D030801:Animals, Genetically Modified; D020869:Gene Expression Profiling; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000235:genetics; D012799:Sialyltransferases / Q000235:genetics; D013045:Species Specificity; D014158:Transcription, Genetic
C473112:Ren2 protein, mouse; D012799:Sialyltransferases; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase; D012083:Renin