Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension.

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear.

Minimal role for the alternative pathway in complement activation by HIT immune complexes.

Background: Anti-platelet factor 4 (PF4)/heparin immune complexes that cause heparin-induced thrombocytopenia (HIT) activate complement via the classical pathway. Previous studies have shown that the alternative pathway of complement substantially amplifies the classical pathway of complement activation through the C3b feedback cycle.

Objectives: These studies sought to examine the contributions of the alternative pathway to complement activation by HIT antibodies.

Redox Activation of Nox1 (NADPH Oxidase 1) Involves an Intermolecular Disulfide Bond Between Protein Disulfide Isomerase and p47 in Vascular Smooth Muscle Cells.

Objective- PDI (protein disulfide isomerase A1) was reported to support Nox1 (NADPH oxidase) activation mediated by growth factors in vascular smooth muscle cells. Our aim was to investigate the molecular mechanism by which PDI activates Nox1 and the functional implications of PDI in Nox1 activation in vascular disease. Approach and Results- Using recombinant proteins, we identified a redox interaction between PDI and the cytosolic subunit p47 in vitro.

Involvement of inducible nitric oxide synthase and estrogen receptor ESR2 (ERβ) in the vascular dysfunction in female type 1 diabetic rats.

Aims: Inflammation is involved in diabetes-related vascular dysfunction. Estrogen receptor ESR2/ERβ induces the expression of inducible nitric oxide (NO) synthase (iNOS) and inflammation. The present study investigated the effect of alloxan-induced type 1 diabetes on the iNOS and ESR2 expression and the effect of the chronic iNOS inhibition on the vascular smooth muscle dysfunction in diabetic female rats.

Intrauterine and lactational exposure to fluoxetine enhances endothelial modulation of aortic contractile response in adult female rats.

The study aimed to evaluate if maternal exposure to fluoxetine (FLX) during pregnancy and lactation would result in altered aortic reactivity in adult offspring. We also sought to understand the role of endothelium derived relaxing factors in aortic response. Wistar rats (75–80 days old), whose progenitors had received FLX (5 mg/kg, FLX offspring) or tap water (control offspring) during pregnancy and lactation were anesthetized, after which the aorta was removed and cut into two rings, one with (Endo+) and the other without (Endo-) endothelium.

Protein disulfide isomerase expression increases in resistance arteries during hypertension development. Effects on Nox1 NADPH oxidase signaling.

NADPH oxidases derived reactive oxygen species (ROS) play an important role in vascular function and remodeling in hypertension through redox signaling processes. Previous studies demonstrated that protein disulfide isomerase (PDI) regulates Nox1 expression and ROS generation in cultured vascular smooth muscle cells. However, the role of PDI in conductance and resistance arteries during hypertension development remains unknown.

Role of nitric oxide and endothelin in endothelial maintenance of vasoconstrictor responses in aortas of diabetic female rats.

Background: Diabetes differentially affects the vascular system in males and females. Although various results have been reported, very few studies have focused on responses in females. In the present study, we investigated contractile responses to norepinephrine in aortas of alloxan-diabetic female rats and evaluated endothelial modulation of these responses.

Role of Ca2+ in the control of H2O2-modulated phosphorylation pathways leading to eNOS activation in cardiac myocytes.

Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) play key roles in physiological and pathological responses in cardiac myocytes. The mechanisms whereby H(2)O(2)-modulated phosphorylation pathways regulate the endothelial isoform of nitric oxide synthase (eNOS) in these cells are incompletely understood. We show here that H(2)O(2) treatment of adult mouse cardiac myocytes leads to increases in intracellular Ca(2+) ([Ca(2+)](i)), and document that activity of the L-type Ca(2+) channel is necessary for the H(2)O(2)-promoted increase in sarcomere shortening and of [Ca(2+)](i).

Angiotensin-II and MARCKS: a hydrogen peroxide- and RAC1-dependent signaling pathway in vascular endothelium.

MARCKS is an actin-binding protein that modulates vascular endothelial cell migration and cytoskeleton signaling (Kalwa, H., and Michel, T. (2011) J.