Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils.

Microparticles from various cells are generated during inflammation. Platelet-derived microparticles (PMPs) harbor receptors that are not genuinely expressed by neutrophils. We tested whether or not functional glycoprotein IIb/IIIa (GPIIb/IIIa) receptors can be acquired by neutrophils via PMPs and whether these receptors participate in pro-inflammatory signaling.

Vascular endothelial cell-specific NF-kappaB suppression attenuates hypertension-induced renal damage.

Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (Tie-1-DeltaN mice) overexpression.

Sympathetic nerve traffic and circulating norepinephrine levels in RGS2-deficient mice.

Regulator of G protein signaling 2 (RGS2-/-) deficient mice feature an increased resting blood pressure and an excessive pressor response to stress. We measured renal sympathetic nerve activity (RSNA) directly to test the hypothesis that RSNA is increased in RGS2-/- mice, compared to RGS2+/+ mice. Seventeen mice (RGS2-/-, n=9; RGS2+/+, n=8) were anesthetized with isoflurane.

Angiotensin II-induced sudden arrhythmic death and electrical remodeling.

Rats harboring the human renin and angiotensinogen genes (dTGR) feature angiotensin (ANG) II/hypertension-induced cardiac damage and die suddenly between wk 7 and 8. We observed by electrocardiogram (ECG) telemetry that ventricular tachycardia (VT) is a common terminal event in these animals. Our aim was to investigate electrical remodeling.

Aldosterone, mineralocorticoid receptors, and vascular inflammation.

Purpose Of Review: Aldosterone and its mineralocorticoid receptor represent an ancient signaling system. Indeed, the mineralocorticoid receptor is older than its agonist. Both have probably served various functions through the eons and salt preservation may be relatively recent.

Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia.

The renin-angiotensin system (RAS) participates in preeclampsia; however, the relative contributions from the circulating RAS and the tissue-based, uteroplacental RAS are unknown. We hypothesized that the tissue-based uteroplacental RAS is dysregulated in preeclampsia. We performed microarray and gene expression studies and confirmed the findings on the protein level by immunohistochemistry in ureteroplacental units from 10 preeclamptic women and 10 women with uneventful pregnancies.

NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils.

Antineutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase 3 (PR3) are central to a form of ANCA-associated vasculitis. Membrane PR3 (mPR3) is expressed only on a subset of neutrophils. The aim of this study was to determine the mechanism of PR3 surface expression on human neutrophils.

p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage.

We investigated whether or not p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGRs). dTGR, with or without p38 inhibitor (BIRB796; 30 mg/kg per day in the diet), and nontransgenic Sprague-Dawley rats were studied in 2 protocols.

Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous heart-muscle disorder characterized by progressive fibrofatty replacement of right ventricular myocardium and an increased risk of sudden cardiac death. Mutations in desmosomal proteins that cause ARVC have been previously described; therefore, we investigated 88 unrelated patients with the disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We identified a heterozygous splice-acceptor-site mutation in intron 5 (c.

Major histocompatibility complex HLA region largely explains the genetic variance exercised on neutrophil membrane proteinase 3 expression.

ANCA-associated vasculitides, a common cause of rapidly progressive glomerulonephritis, are influenced by genetic variance. Neutrophil membrane expression of the ANCA antigen proteinase 3 (PR3) is pathogenically important. A subset of membrane PR3-positive neutrophils can be distinguished from a membrane-negative subset in any given subject.

Angiotensin type 1 receptor antagonists induce human in-vitro adipogenesis through peroxisome proliferator-activated receptor-gamma activation.

Objective: In clonal animal cells, certain angiotensin receptor blockers (ARB) activate the peroxisome proliferator-activated receptor-gamma (PPARgamma). The aim of this work was to validate that observation in human cells and humans.

Methods: We investigated the induction of in-vitro adipogenesis and the activation of PPARgamma-target genes, adiponectin and lipoprotein lipase, by ARB in human preadipocytes.

Apoptosis, proliferation and inflammatory infiltration in ANCA-positive glomerulonephritis.

Aims: Antineutrophil cytoplasmic antibodies (ANCA) are detected in most patients with crescentic glomerulonephritis and necrotizing small vessel vasculitis. ANCA cause renal inflammation and proliferation. Apoptosis is necessary for resolution of inflammation.