Arteriosclerosis, thrombosis, and vascular biology
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Arterioscler. Thromb. Vasc. Biol. · Sep 2013
Multicenter Study Meta AnalysisRisk scores of common genetic variants for lipid levels influence atherosclerosis and incident coronary heart disease.
Circulating levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides are recognized risk factors for cardiovascular disease. We tested the hypothesis that the cumulative effects of common genetic variants for lipids are collectively associated with subclinical atherosclerosis and incident coronary heart disease. ⋯ Common genetic variants with small effects on lipid levels are, in combination, significantly associated with subclinical and clinical cardiovascular outcomes. As knowledge of genetic variation increases, preclinical genetic screening tools might enhance the prediction and prevention of clinical events.
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Arterioscler. Thromb. Vasc. Biol. · Sep 2013
Comparative StudySmad2-dependent protease nexin-1 overexpression differentiates chronic aneurysms from acute dissections of human ascending aorta.
Tissue activation of proteolysis is involved in acute intramural rupture (dissections, acute ascending aortic dissection) and in progressive dilation (aneurysms, thoracic aneurysm of the ascending aorta) of human ascending aorta. The translational aim of this study was to characterize the regulation of antiproteolytic serpin expression in normal, aneurysmal, and dissecting aorta. ⋯ These results demonstrate that epigenetically regulated PN-1 overexpression promotes development of an antiproteolytic VSMC phenotype and might favor progressive aneurysmal dilation, whereas absence of this counter-regulation in dissections would lead to acute wall rupture.
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Arterioscler. Thromb. Vasc. Biol. · Sep 2013
Basilar artery diameter is an independent predictor of incident cardiovascular events.
Basilar arterial (BA) dolichoectasia is associated with cerebral small-vessel disease and stroke. However, the association between moderate dilation of the BA and cerebral small-vessel disease or subsequent cardiovascular events remains unclear. This study aims to clarify the factors related to BA diameter and to clarify whether the BA diameter is an independent predictor of cardiovascular events. ⋯ Increased BA diameter within the normal range is related to both large-vessel disease and cerebral small-vessel disease, and it could be a new predictor of cardiovascular events.
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Arterioscler. Thromb. Vasc. Biol. · Sep 2013
Atrial natriuretic peptide-mediated inhibition of microcirculatory endothelial Ca2+ and permeability response to histamine involves cGMP-dependent protein kinase I and TRPC6 channels.
Histamine increases microvascular endothelial leakage by activation of complex calcium-dependent and -independent signaling pathways. Atrial natriuretic peptide (ANP) via its cGMP-forming guanylyl cyclase-A (GC-A) receptor counteracts this response. Here, we characterized the molecular mechanisms underlying this interaction, especially the role of cGMP-dependent protein kinase I (cGKI). ⋯ ANP attenuates the inflammatory actions of histamine via endothelial GC-A/cGMP/cGKI signaling and inhibitory phosphorylation of TRPC6 channels. The therapeutic potential of this novel regulatory pathway is indicated by the observation that sildenafil improves systemic endothelial barrier functions by enhancing the endothelial effects of endogenous ANP.
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Arterioscler. Thromb. Vasc. Biol. · Sep 2013
Toll-like receptor 2/6 agonist macrophage-activating lipopeptide-2 promotes reendothelialization and inhibits neointima formation after vascular injury.
Reendothelialization after vascular injury (ie, balloon angioplasty or stent implantation) is clinically extremely relevant to promote vascular healing. We here investigated the therapeutic potential of the toll-like receptor 2/6 agonist macrophage-activating lipopeptide (MALP)-2 on reendothelialization and neointima formation in a murine model of vascular injury. ⋯ The toll-like receptor 2/6 agonist MALP-2 promotes reendothelialization and inhibits neointima formation after experimental vascular injury via enhanced proliferation and migration of endothelial cells. Thus, MALP-2 represents a novel therapeutic option to accelerate reendothelialization after vascular injury.