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One of the major cardiovascular risk factor which predisposes to and accelerates atherosclerosis is arterial hypertension (AH). To determine the molecular basis of the crosslink between AH and atherosclerosis for the development of new treatment strategies large-scale transcriptome analysis of the cells implicated in atherogenesis is needed. We used cDNA microarray technique for simultaneous analysis of gene expression in human abdominal aorta normal sites and atherosclerotic lesions of different histological types, as well as in peripheral blood leukocytes from patients with essential hypertension (EH) and donors. The microarray data were verified by quantitative RT-PCR (reverse transcription coupled with polymerase chain reaction) and immunohistochemical analysis. Differential expression of 40 genes has been found, among which twenty two genes demonstrated up-regulation and 18 genes demonstrated down-regulation in atherosclerotic aorta compared with normal vessel. New gene-candidates, implicated in atherogenesis, have been identified - FPRL2, CD37, CD53, RGS1, LCP1, SPI1, CTSA, EPAS1, FHL1, GEM, RHOB, SPARCL1, ITGA8, PLN, and COL14A1. These genes participate in cell migration and adhesion, phenotypic changes of smooth muscle cells, immune and inflammatory reactions, oxidative processes and extracellular matrix remodeling. We have found increased expression levels of CD53, SPI1, FPRL2, SPP1, CTSD, ACP5, LCP1, CTSA and LIPA genes in peripheral blood leukocytes from EH patients and in atherosclerotic lesions of human aorta. The majority of these genes significantly (p<0.005) positively (r>0.5) correlated with AH stage as well as with histological grading of atherosclerotic lesions.

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.

Aim: To study a correlation between lipoprotein(a) [LP(a)], as well as the phenotype of apoprotein(a) [apo(a)] and the presence of intermittent claudication (IC)., Materials and Methods: The study included 25 patients (9 females, 16 males; mean age, 63.4 +/- 8.2 years) and 50 individuals (21 females, 29 males; mean age, 61.3 +/- 6.1 years) of a control group., Results: In the patients, the level of LP(a) was 3 times higher than in the controls (median 39 and 13 mg/dl, respectively; p < 0.01). The low molecular-weight phenotypes of apo(a) occurred significantly more frequently in the patients than those in the controls (62 and 28%, respectively; p = 0.02)., Conclusion: Multifactorial analysis has shown that the level of Lp(a) is an independent and important factor associated with the presence of IC.

Relationship between level of lipoprotein (a) and presence of ischemic heart disease (IHD) was studied in 191 patients with hypertensive disease (essential hypertension) (112 men, 79 women, age 56.9-/+10.6 years) and 33 patients with normal blood pressure (23 men, 10 women, age 50.8-/+11.0 years). Concentration of lipoprotein (a) in men with hypertension and IHD (n=62) was significantly higher than in men with hypertension without IHD (n=50) (median 19 and 9 mg/dl, respectively, p=0.02). Women with hypertension and with (n=23) and without (n=56) IHD had similar blood levels of lipoprotein (a) (median 13 and 15 mg/dl, respectively, p=0.89). Difference in lipoprotein (a) levels between patients with hypertensive disease and those with normal blood pressure was not significant (median 14 and 10 mg/dl, respectively, p=0.50).