Details

Autor(en) / Beteiligte

• Klett, Christoph P.R.
• Kelley, KaShonda L.
• Sirous, Zohrea N.

Titel

P-382: Changes in gene expression profiles of left ventricles in aging normotensive (WKY) and spontaneously hypertensive rats (SHR)

Ist Teil von

• American journal of hypertension, 2002-04, Vol.15 (S3), p.169A-169A

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2002

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Spontaneously hypertensive rats (SHR) develop elevated blood pressure between the age of 4 and 8 weeks. Left ventricular hypertrophy accompanies the onset of hypertension and was considered to be a benign adaptive cardiac process. However, more recently it was hypothesized that left ventricular hypertrophy as well as other structural changes in the left ventricle may be related to blood pressure independent pathologic or pathophysiologic factors. In our present study we addressed this issue by establishing gene expression profiles of left ventricles isolated from SHR and their normotensive control strain, the Wistar Kyoto rat (WKY) for 2400 genes before (age of 4 weeks) and after (age of 4 months)the development of high blood pressure. At the given age from each strain 4 left ventricles were prepared and total RNA was isolated according to the LiCl/urea method. DNP or biotin labeled cDNAs were synthesized, competitively hybridized to microarrays and detected by Cyanine-3 or Cyanine-5 tyramide labeled antibodies directed against DNP or biotin, respectively. In the left ventricle of 4 week old rats structural elements (e.g. myosin, actin bundling protein, myosin regulatory light chain, or 20 kDa myosin light chain 3.2 ± 0.4 fold), factors related to protein synthesis in general (ribosomal proteins, splicing factor, DNA binding proteins, elongation factor 1 alpha, 2.3 - 6.7 fold), angiotensinogen (3.1 ± 0.3 fold), determinants of membrane conductance and ion transport (e.g. Na/K ATPase 2.8 ± 0.5 fold; voltage dependent anion channel 2.7 ± 0.4 fold), apoptotic factors (e.g. 14-3-3 epsilon and 23 kDa highly basic protein (4.5 - 6.5 fold), and components of the cytochrome C pathway where some of the genes with enhanced expression. In adult SHR the determinants of membrane conductance and ion transport were overexpressed at a significant higher level than at the age of 4 weeks in comparison to WKY, while a significant inhibition in the expression of structural elements was observed at this age. In adult animals extracellular and Cu/Zn superoxide dismutase were overexpressed 1.8 - 2.1 fold. We conclude that significant up-regulation of gene expression occurs in left ventricles of SHR already before the establishment of hypertension. Microarray analysis provides new and more complex insights into cardiac pathways abnormally regulated during and after the pathogenesis of hypertension and may be a helpful tool to discriminate between causes and consequences of various disease states.