Broadly Altered Gene Expression in Blood Leukocytes in Essential Hypertension Is Absent During Treatment

Abstract

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.

Prediction of Ischemic Events on the Basis of Transcriptomic and Genomic Profiling in Patients Undergoing Carotid Endarterectomy

“…The method may be developed to identify subjects at very high risk of ischemic events. Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00479 tients, healthy controls and patients with thoracic aortic aneurysm, as well as patients differing in their extent of coronary artery disease (6)(7)(8)(9)(10). Other studies have examined diseased tissue biopsied from the site of disease, with a similar aim of identifying disease-specific gene expression (11)(12)(13)(14)(15).…”

Association of white blood cell count with systolic blood pressure within the normotensive range

“…1 Hypertension is a major risk factor for atherosclerosis, cardiovascular disease (CVD) and stroke. 2 The relationship between blood pressure and risk of CVD is continuous, consistent, and independent of other risk factors. For individuals aged 40-70 years, each increment of 20 mm Hg in systolic blood pressure (SBP) or 10 mm Hg in diastolic blood pressure (DBP) doubles the risk of CVD across the entire blood pressure range from 115/75 to 185/115 mm Hg.…”

Disturbed circadian blood pressure rhythm and C-reactive protein in essential hypertension

“…3 In experimental models of hypertension, vascular-wall remodelling and inflammatory infiltration have been observed, 4 whereas the expression of several genes related to the modification of the inflammatory response has been found altered in the leukocytes of human untreated hypertensive subjects. 5 Furthermore, the association of microalbuminuria and left ventricular concentric remodelling with increased hs-CRP supports the participation of inflammatory mechanisms in the manifestation of target organ damage in essential hypertensives. 6,7 Subjects with blunted nocturnal fall in blood pressure (BP), defined as non-dippers, exhibit a higher prevalence of target organ damage such as left ventricular hypertrophy, microalbuminuria, silent cerebrovascular disease and peripheral arterial changes, 8 thus being at higher risk for cardiovascular events.…”