Analyses of differential gene expression in genetic hypertensive rats by microarray

Area of Science:

• Genetics
• Cardiovascular Biology
• Pharmacology

Background:

• Spontaneously hypertensive rats (SHR) are a widely used genetic model for human hypertension.
• Identifying genes associated with hypertension is crucial for understanding disease mechanisms and developing targeted therapies.

Purpose of the Study:

• To identify genes differentially expressed between SHR and Wistar-Kyoto rats (WKY) and analyze their correlation with hypertension.
• To investigate the genetic basis of hypertension using a combination of microarray analysis, cosegregation analysis, and quantitative trait loci (QTL) mapping.

Main Methods:

• cDNA microarray analysis was performed to identify differentially expressed genes between SHR and WKY rats.
• Eleven selected genes underwent F2 cosegregation analysis in 105 F2 rats derived from SHR and WKY.
• Blood pressure was measured directly, and quantitative trait loci (QTL) analysis was conducted.

Main Results:

• Twenty-four genes were up-regulated and 20 down-regulated in SHR compared to WKY.
• Genotypes of monocarboxylate transporter 1 (MCT1) and glutathione S-transferase Y(b) subunit (Gst Y(b)) significantly affected diastolic blood pressure in F2 rats.
• QTL analysis confirmed these two genes, located on chromosome 2, influenced diastolic blood pressure.
• Antihypertensive treatment with enalapril or hydralazine only affected Hsp70 expression, with hydralazine up-regulating it.

Conclusions:

• While MCT1 and Gst Y(b) showed a genetic association with diastolic blood pressure in this model, the overall identification of differentially expressed genes may not be an efficient strategy for selecting hypertension candidate genes in the SHR-WKY system.
• Further research is needed to elucidate the complex genetic architecture of hypertension.