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Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES−/− knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES−/−), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8+ and double-negative CD3+CD4−CD8− T cells in perivascular space and reduced vascular oxidative stress while FoxP3+ T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = −0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.—Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension.

We have shown that T cells are involved in the genesis of hypertension, but the subset(s) involved have not been defined. T cell activation involves clonal expansion of cells with unique T cell rec...

Hypertension is associated with increased sympathetic outflow and subsequent activation of adaptive immunity. We hypothesized that renal sympathetic nerves activate dendritic cells, and that these ...

Objective: To determine if food insecure households are more likely to skip, delay or reduce medications to compensate for lack of household resources to purchase food. Methods: We used data from a combined sample of the 2011 and 2012 National Health Interview Survey (n=52,699). We conducted bivariate and logistic regression analyses to examine the association between food security (FS) and medication use; controlling for demographics, lifestyle, BMI, chronic disease, disability, health care coverage and self-rated health. Sample weights were applied to account for the complex sample design. Results: Seventy eight percent of respondents reported high FS, 8% marginal FS, 6.9% low FS and 6.0% very low FS. Seven percent reported skipping medications; 7.6% used fewer medications; 9.4% delayed filling a prescription; and 20% lowered the dose of medication. Net of other factors the odds of skipping medications increased with increasing severity of food insecurity (OR of 1.67 for marginal FS, 2.86 for low FS and...

T cell mitochondrial ROS in development of hypertension Rafal R. Nazarewicz*, Anna Dikalova*, Alfiya Bikineyeva*, Rob Egnatchik#, Jamey Young#, David G. Harrison*, Sergey Dikalov* Division of Clini...

Fatty acid oxidation leads to formation of highly reactive γ-ketoaldehydes termed isoketals that adduct to protein lysines. We have shown that hypertension causes isoketals to accumulate in dendrit...

We have previously shown that the pro-inflammatory cytokine, interleukin 17A (IL17A), is upregulated by angiotensin II and plays a critical role in angiotensin II induced hypertension and vascular ...

The purpose of this study was to characterize the effect of various shear conditions on endothelial cell intracellular calcium ([Ca2+]i). Bovine aortic endothelial cells (BAEC) were loaded with Fluo-3 and exposed to flow in a parallel plate flow chamber designed for confocal microscopy. The flow medium was medium 199 (M-199), which was prepared with and without adenosine triphosphate (ATP). In the presence of ATP, initiation of flow at a shear stress of 2.5 dyn/cm2 evoked a strong, sustained elevation of [Ca2+]i that gradually returned to baseline levels over 10 to 15 min. By contrast, in the absence of ATP, initiation of flow at 2.5 dyn/cm2 produced only transient increases in [Ca2+]i in a small proportion of the cells. As shear rate was increased from 2.5 to 15 dyn/cm2 in this medium, both the relative fluorescence of the monolayer and the proportion of cells across the monolayer that displayed calcium transients increased in a dose-dependent fashion. In conclusion, the response of an endothelial cell monolayer to increasing levels of shear is not only to increase [Ca2+]i within individual cells, but to increase the duration of response and the number of cells responding at the onset of shear. This recruitment of larger numbers of cells at higher levels of shear may represent a novel signaling mechanism within the endothelium.