Carotid arteriotomy induces different temporal gene expression profiles in normotensive and hypertensive rat strains

Abstract

Analysis of gene expression profiles in patients or in animal models affected by cardiovascular diseases may provide insight into therapeutic strategies. In this study, 3 rat strains, Wistar Kyoto (WKY), spontaneously hypertensive rats (SHR) and the Milan hypertensive rat strain (MHS), have been investigated to assess the influence of genetic background and/or of hypertension on gene expression in arteriotomy-injured carotid arteries (CAs). Expression profiles of genes, c-myc, AT1, AT2, ETA, ETB, Bcl-2, Bax and Bcl-X, were determined by reverse transcription-polymerase chain reaction (RT-PCR) in the acute phase, from 1 to 48 h, following CA arteriotomy. WKY, SHR and MHS show significant differences in gene expression profiles after CA arteriotomy. c-Myc mRNA is activated earlier and/or to a greater extent in hypertensive strains than in WKY (p<0.05). AT1 mRNA increases in WKY after injury, while it decreases in both SHR and MHS (p<0.05). AT2 shows the opposite behaviour, decreasing in WKY and increasing in hypertensive strains (p<0.05). ETA mRNA decreases in all strains although with different timing and levels, associated with a replacement by ETB mRNA (p<0.05). Bcl-2/Bax ratio gradually decreases in WKY, while it decreases only transiently in SHR and MHS 4 h after injury (p<0.05). Overall data indicate that therapeutic strategies for stenosis prevention should carefully consider the gene expression profile after injury, the genetic background, the kind of vascular trauma and the diseases affecting the animal model or the patient.