Altered Genes Profile of Renin–Angiotensin System, Immune System, and Adipokines Receptors in Leukocytes of Children With Primary Hypertension

Abstract

Abstract-Renin-angiotensin system, metabolic abnormalities, and immune activity have a role in the pathogenesis of primary hypertension. We assessed the leukocyte mRNA expression of angiotensinogen, angiotensin converting enzyme, renin, angiotensin 2 type 1 receptor, CD14 molecule, adiponectin type 1 receptor, and leptin receptor in hypertensive children before and after nonpharmacological treatment. Leukocyte mRNA expression was measured by means of quantitative real-time reverse transcriptase-polymerase chain reaction in 23 hypertensive children before and after 6 months of nonpharmacological treatment based on dietary advice and physical activities. Twenty-three normotensive children matched for age, sex, and body mass index served as a control group. Before treatment patients had elevated expression of angiotensin converting enzyme and CD14 mRNA, decreased expression of angiotensinogen and angiotensin type 1 receptor mRNA, and unchanged expression of renin, adiponectin, and leptin receptors mRNA as compared with controls. Renin mRNA negatively correlated with 24-hour mean arterial pressure and carotid intima-media thickness. Six months of nonpharmacological treatment caused decrease of blood pressure and normalization of metabolic abnormalities. Renin, adiponectin, and leptin receptors mRNA expression decreased and were lower than in control group. Changes in blood pressure, left ventricular mass, carotid intima-media thickness, body mass index, and waist circumference did not correlate with changes in the expression of renin-angiotensin system genes, CD14, leptin, and adiponectin receptors mRNA. We conclude that leukocytes of hypertensive children displayed alterations in the expression of renin-angiotensin system genes as well as those of CD14. Nonpharmacological treatment resulted in downregulation of genes involved in reninangiotensin activation and those engaged in leukocyte responses to adipokines. (Hypertension. 2013;61:431-436.)

Primary Hypertension in Children and Adolescents is an Immuno-Metabolic Disease with Hemodynamic Consequences

“…Angiotensinogen (AGT) and AT2 type 1 receptor (AT2R1) mRNAs expression were down regulated. Moreover, children with increased cIMT had significantly lower renin (REN) mRNA expression [38]. The reason for that is not clear, but strongly suggests that RAS system in PBL must be activated early in the course of PH.…”

Expression of Adiponectin Receptors on Peripheral Blood Leukocytes of Hypertensive Children Is Associated with the Severity of Hypertension

“…Similarly, PBLs from PH children have been revealed to show an altered expression of inflammatory molecules and elements of renin-angiotensin system. This altered pattern of gene expression changed during nonpharmacological treatment [4]. …”

“…Total RNA was isolated with Chomczyński method using Trizol Reagent (Invitrogen), as described previously [4, 19]. RNA sample concentration was determined spectrophotometrically at 260 nm, and the purity was confirmed by 260/280 ratio.…”

“…The specificity of the amplification reaction was verified by analyzing the melting curve. The gene expression level was expressed as fold change of target gene expression according to basic level (=1) of the same gene expression in the control group's leukocytes, after normalization by expression of the reference gene G3PDH, by using Pfaffl's mathematical model, as previously described [4, 20]. All reagents, equipment, and other supplies for Q-PCR technique were provided by Applied Biosystems (now Life Technologies).…”

“…It was found that the serum systemic inflammatory markers, including C-reactive protein, cytokines, and chemokines, are related mainly to metabolic abnormalities and oxidative stress components or even to target organ damage (TOD) but are rather weakly associated with blood pressure elevation per se [3]. Recently we found that peripheral blood leukocytes (PBLs) of PH children showed an upregulation of renin-angiotensin system (RAS) genes [4]. These observations, as well as other results, may indicate that leukocyte activation profiles are much more related to blood pressure elevation than the serum acute phase response components.…”