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Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques.

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TLDR
It is suggested that in vivo local shear stress influences luminal endothelial cell apoptosis and may be a major determinant of plaque erosion and thrombosis.
Abstract
Background—Blood flow characteristics influence endothelial cell apoptosis. However, little is known about the occurrence of endothelial cell apoptosis in human atherosclerosis and its relation to blood flow. Methods and Results—A total of 42 human carotid atherosclerotic plaques were retrieved by endarterectomy; they were examined in the longitudinal axial direction. Plaques were included in this study when upstream and downstream parts were clearly visible, occlusion was absent, and immunostaining for luminal endothelium was present all along the plaque. Using these criteria, 13 plaques were processed for further immunohistochemical studies (using anti-CD31, anti-Ki-67, and anti-splicing factor antibodies) and in situ detection of apoptosis (terminal dUTP nick end-labeling and ligase assay). Eight plaques showed ≥1 apoptotic endothelial cell at the luminal surface. Quantitative analysis of endothelial cell apoptosis in these plaques showed a systematic preferential occurrence of apoptosis in the downstr...

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Citations
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Vascular Smooth Muscle Cells in Atherosclerosis

TL;DR: There is now compelling evidence that a full understanding of VSMC behavior in Atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis.
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Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior.

TL;DR: The molecular, cellular, and vascular processes supporting the role of low ESS in the natural history of coronary atherosclerosis and vascular remodeling are explored and likely mechanisms concerning the different natural history trajectories of individual coronary lesions are indicated.
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Role of oxidative stress in atherosclerosis

TL;DR: Oxidative stress in humans with coronary artery disease is also exacerbated by a reduction of vascular extracellular superoxide dismutase, normally an important protective enzyme against the superoxide anion.
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Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis

TL;DR: It is shown that in models of post-angioplasty restenosis, graft vasculopathy and hyperlipidemia-induced atherosclerosis, bone-marrow cells give rise to most of the SMCs that contribute to arterial remodeling, indicating that somatic stem cells contribute to pathological remodeling of remote organs.
References
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Journal ArticleDOI

Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation

TL;DR: It is demonstrated that the serine/threonine protein kinase Akt/PKB mediates the activation of eNOS, leading to increased NO production, and represents a novel Ca2+-independent regulatory mechanism for activation ofeNOS.
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Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress.

TL;DR: These studies confirm earlier findings under steady flow conditions that plaques tend to form in areas of low, rather than high, shear stress, but indicate in addition that marked oscillations in the direction of wall shear may enhance atherogenesis.
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Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress.

TL;DR: It is concluded that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening.
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Atheroma and arterial wall shear. Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis.

TL;DR: It appears that wall shear rate may be a major controlling factor in the development of atheromatous lesions in man and in animals and a net flux of cholesterol from blood to wall cannot account for the observed normally occurring (quasi-steady state) and experimentally induced atheroma.
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Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death.

TL;DR: Erosion of proteoglycan-rich and smooth muscle cell-rich plaques lacking a superficial lipid core or plaque rupture is a frequent finding in sudden death due to coronary thrombosis, comprising 44% of cases in the present study.
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