Broadly altered gene expression in blood leukocytes in essential hypertension is absent during treatment.
We assessed whether large-scale expression profiling of leukocytes of patients with essential hypertension reflects characteristics of systemic disease and whether such changes are responsive to antihypertensive therapy. Total RNA from leukocytes were obtained from untreated (n=6) and treated (n=6) hypertensive patients without apparent end-organ damage and from normotensive controls (n=9). RNA was reverse-transcribed and labeled and gene expression analyzed using a 19-K oligonucleotide microarray using dye swaps. Samples of untreated and of treated patients were pooled for each sex and compared with age- and sex-matched controls. In untreated patients, 680 genes were differentially regulated (314 up and 366 down). In the treated patients, these changes were virtually absent (4 genes up, 3 genes down). A myriad of changes was observed in pathways involved in inflammation. Inflammation-dampening interleukin receptors were decreased in expression. Intriguingly, inhibitors of cytokine signaling (the PIAS family of proteins) were differentially expressed. The expression of several genes that are involved in regulation of blood pressure were also differentially expressed: angiotensin II type 1 receptor, ANP-A receptor, endothelin-2, and 3 of the serotonin receptors were increased, whereas endothelin-converting enzyme-1 was decreased. Strikingly, virtually no changes in gene expression could be detected in hypertensive patients who had become normotensive with treatment. This observation substantiates the long-standing idea that hypertension is associated with a complex systemic response involving inflammation-related genes. Furthermore, leukocytes display differential gene expression that is of importance in blood pressure control. Importantly, treatment of blood pressure to normal values can virtually correct such disturbances.
Department of Nephrology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
Helena
H
Chon
Carlo A J M
CA
Gaillard
Brenda B
BB
van der Meijden
Hilde M
HM
Dijstelbloem
Rob J
RJ
Kraaijenhagen
Dik
D
van Leenen
Frank C P
FC
Holstege
Jaap A
JA
Joles
Hans A R
HA
Bluyssen
Hein A
HA
Koomans
Branko
B
Braam
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D007249:Inflammation / Q000097:blood / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical
D000959:Antihypertensive Agents