Altered gene expression pattern in peripheral blood leukocytes from patients with arterial hypertension.
The role of various inflammatory mechanisms and oxidative stress in the development of atherosclerosis and arterial hypertension (AH) has been increasingly acknowledged during recent years. Hypertension per se or factors that cause hypertension along with other complications lead to infiltration of activated leukocytes in the vascular wall, where these cells contribute to the development of vascular injury by releasing cytokines, oxygen radicals, and other toxic mediators. However, molecular mechanisms underlying leukocyte activation at transcriptional level in AH are still far from being clear. To solve this problem we employed cDNA microarray technology to reveal the differences in gene expression in peripheral blood leukocytes from patients with AH compared with healthy individuals. The microarray data were verified by a semi-quantitative RT-PCR method. We found 25 genes with differential expression in leukocytes from AH patients among which 21 genes were upregulated and 4 genes were downregulated. These genes are implicated in apoptosis (CASP2, CASP4, and CASP8, p53, UBID4, NAT1, and Fte-1), inflammatory response (CAGC, CXCR4, and CX3CR1), control of MAP kinase function (PYST1, PAC1, RAF1, and RAFB1), vesicular trafficking of molecules among cellular organelles (GDI-1 and GDI-2), cell redox homeostasis (GLRX), cellular stress (HSPA8 and HSP40), and other processes. Gene expression pattern of the majority of genes was similar in AH patients independent of the disease stage and used hypotensive therapy, but was clearly different from that of normotensive subjects.
Timofeeva
A V
AV
Russian Cardiology Reseach and Production Center, Laboratory of Genetic Engineering, 3rd Cherepkovskaya str. 15a, 121552 Moscow, Russia. Angelica_T@cardio.ru
Goryunova
L E
LE
Khaspekov
G L
GL
Kovalevskii
D A
DA
Scamrov
A V
AV
Bulkina
O S
OS
Karpov
Yu A
YA
Talitskii
K A
KA
Buza
V V
VV
Britareva
V V
VV
Beabealashvilli
R Sh
RSh
D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis