Physiological genomics
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Physiological genomics · Aug 2012
Mechanisms of cardioprotection resulting from Brown Norway chromosome 16 substitution in the salt-sensitive Dahl rat.
The SS-16(BN)/Mcwi consomic rat was produced by the introgression of chromosome 16 from the Brown Norway (BN/NHsdMcwi) rat onto the genetic background of the Dahl salt-sensitive (SS/Mcwi) rat by marker-assisted breeding. We have previously shown that the normotensive SS-16(BN)/Mcwi consomic strain is better protected from developing left ventricular dysfunction and fibrosis with aging than the hypertensive SS/Mcwi parental strain; however, the mechanism of this protection was not clear since the SS-16(BN)/Mcwi had both lowered blood pressure and an altered genetic background compared with SS/Mcwi. Microarray analysis of SS-16(BN)/Mcwi and SS/Mcwi left ventricle tissue and subsequent protein pathway analysis were used to identify alterations in gene expression in signaling pathways involved with the observed cardioprotection on the SS background. ⋯ We also demonstrate that the SS-16(BN)/Mcwi is better protected from developing fibrosis with surgically elevated afterload than other normotensive strains, indicating that gene-gene interactions resulting from BN chromosomal substitution confer specific cardioprotection. When combined with our previous findings, these data suggest that that SS-16(BN)/Mcwi may have an increased angiogenic potential and better protection from oxidative stress than the parental SS/Mcwi strain. Additionally, the early transient idiopathic left ventricular hypertrophy in the SS-16(BN)/Mcwi may be related to altered myocyte sensitivity to growth factors.