Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Nov 2013
Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus.
Human cytomegalovirus (HCMV), a pathogen involved in the development and progression of atherosclerosis, promotes in some individuals a marked reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a persistent expansion of a peripheral blood NK-cell subset expressing the CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell compartment reconfiguration is related to carotid atherosclerotic plaque (CAP) instability. ⋯ The expansion of NKG2C+ NK cells in patients with CAP seems to be associated with an increased risk of plaque destabilization in some patients with chronic HCMV infection.
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Arterioscler. Thromb. Vasc. Biol. · Nov 2013
Anti-human neutrophil antigen-3a induced transfusion-related acute lung injury in mice by direct disturbance of lung endothelial cells.
Antibodies against human neutrophil antigen-3a (HNA-3a) located on choline transporter-like protein 2 induce severe transfusion-related acute lung injury (TRALI). This study aims to identify the mechanism implicated in anti-HNA-3a-mediated TRALI. ⋯ These data demonstrate the initiation of endothelial barrier dysfunction in vitro and in vivo by direct binding of anti-HNA-3a on endothelial cells. It seems, however, that the presence of neutrophils aggravates barrier dysfunction. This novel mechanism of TRALI primarily mediated by endothelial cell dysfunction via choline transporter-like protein 2 may help to define new treatment strategies to decrease TRALI-related mortality.
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Arterioscler. Thromb. Vasc. Biol. · Oct 2013
Maternal hypercholesterolemia in pregnancy associates with umbilical vein endothelial dysfunction: role of endothelial nitric oxide synthase and arginase II.
Human pregnancy that courses with maternal supraphysiological hypercholesterolemia (MSPH) correlates with atherosclerotic lesions in fetal arteries. It is known that hypercholesterolemia associates with endothelial dysfunction in adults, a phenomenon where nitric oxide (NO) and arginase are involved. However, nothing is reported on potential alterations in the fetoplacental endothelial function in MSPH. The aim of this study was to determine whether MSPH alters fetal vascular reactivity via endothelial arginase/urea and L-arginine transport/NO signaling pathways. ⋯ MSPH is a pathophysiological condition altering umbilical vein reactivity because of fetal endothelial dysfunction associated with arginase and eNOS signaling imbalance. We speculate that elevated maternal circulating cholesterol is a factor leading to fetal endothelial dysfunction, which could have serious consequences to the growing fetus.
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Arterioscler. Thromb. Vasc. Biol. · Oct 2013
Endoplasmic reticulum stress participates in aortic valve calcification in hypercholesterolemic animals.
Aortic valve (AV) calcification occurs via a pathophysiological process that includes lipoprotein deposition, inflammation, and osteoblastic differentiation of valvular interstitial cells. Here, we investigated the association between endoplasmic reticulum (ER) stress and AV calcification. ⋯ These data provide novel evidence that ER stress participates in AV calcification development, and suggest that ER stress may be a novel target for AV calcification prevention and treatment.
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Arterioscler. Thromb. Vasc. Biol. · Sep 2013
Compartmentalized protective and detrimental effects of endogenous macrophage migration-inhibitory factor mediated by CXCR2 in a mouse model of myocardial ischemia/reperfusion.
Here, we aimed to clarify the role of CXC chemokine receptor (CXCR) 2 in macrophage migration-inhibitory factor (MIF)-mediated effects after myocardial ischemia and reperfusion. As a pleiotropic chemokine-like cytokine, MIF has been identified to activate multiple receptors, including CD74 and CXCR2. In models of myocardial infarction, MIF exerts both proinflammatory effects and protective effects in cardiomyocytes. Similarly, CXCR2 displays opposing effects in resident versus circulating cells. ⋯ The compartmentalized and opposing effects of MIF after myocardial ischemia and reperfusion are largely mediated by CXCR2. Although MIF confers protective effects by improving myocardial healing and function through CXCR2 in resident cells, thereby complementing paracrine effects through CD74/AMP-activated protein kinase, it exerts detrimental effects on CXCR2-bearing inflammatory cells by increasing monocyte infiltration and impairing heart function. These dichotomous findings should be considered when developing novel therapeutic strategies to treat myocardial infarction.