path(HM:"Endothelial dysfunction")
To investigate the direct effects of FeCl3 on aortic endothelium, FeCl3 was perfused through isolated aorta independently of flowing blood. Strikingly no endothelial denudation or collagen exposure was evident following prolonged exposure to FeCl3 (6%) (Fig. 1C). PubMed:19276082
Subsequent perfusion of anticoagulated whole blood through FeCl3-pretreated vessels was associated with an increase in leukocyte and platelet adhesion to the vessel wall (Fig. 1E and supplemental Video 2); however, relative to untreated aorta (Fig. 1F and supplemental Video 3) and treatment in the presence of flowing blood (Fig. 1D and supplemental Video 1), thrombus formation was not observed. PubMed:19276082
In contrast, selectively removing RBCs prevented endothelial denudation and collagen exposure, resulting in a relatively mild perturbation of endothelial function similar to that observed with FeCl3 alone (data not shown). PubMed:19276082
Oxidized LP(ox- LP) then induces toxic effects in endothelial cells [6]. PubMed:26475040
Many studies have explored basic mechanisms of Hb or heme triggered endothelial damage and have suggested that oxidative reactions of Hb generate multiple toxic species such as free heme that is released from ferric Hb, iron, free radicals, and globin aggregation products [15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25]. PubMed:26475040
As shown in Fig 3B, lipids from atherosclerotic lesions were cytotoxic to endothelium, an effect strikingly enhanced when lipids were pre-oxidized by exposure to heme. PubMed:20378845
Many studies have explored basic mechanisms of Hb or heme triggered endothelial damage and have suggested that oxidative reactions of Hb generate multiple toxic species such as free heme that is released from ferric Hb, iron, free radicals, and globin aggregation products [15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25]. PubMed:26475040
Compared to wild-type (WT) mice, mice with 117 endothelial dysfunction have an increased vasoconstrictor response to infusion of 118 cell-free hemoglobin (25). PubMed:28314763
Topical treatment with 6% FeCl3 with hemin (1mM) perfusions caused no greater endothelial injury than FeCl3 or hemin (1 mM) alone (data not shown), whereas FeCl3 in the presence of low concentrations of metHb (0.38 mg/ml) induced extensive vascular injury similar to that observed with FeCl3 in the presence of whole blood (Figs. 4 and 1D, respectively). PubMed:19276082
Third, reintroduction of washed RBCs or purified metHb in the presence of FeCl3 led to a similar level of vascular injury as observed with whole blood, whereas isolated RBC membranes and heme, even in the presence of FeCl3, produced relatively mild injury. PubMed:19276082
We have found that atheroma lipids when oxidized by heme are highly cytotoxic to human endothelial cells, and hemopexin reduced this cytotoxicity. PubMed:20378845
Endothelial dysfunction, a condition associated with reduced bioavailability of 282 vascular NO, occurs in humans and mice with hyperlipidemia (16). PubMed:28314763
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
To investigate the direct effects of FeCl3 on aortic endothelium, FeCl3 was perfused through isolated aorta independently of flowing blood. Strikingly no endothelial denudation or collagen exposure was evident following prolonged exposure to FeCl3 (6%) (Fig. 1C). PubMed:19276082
Subsequent perfusion of anticoagulated whole blood through FeCl3-pretreated vessels was associated with an increase in leukocyte and platelet adhesion to the vessel wall (Fig. 1E and supplemental Video 2); however, relative to untreated aorta (Fig. 1F and supplemental Video 3) and treatment in the presence of flowing blood (Fig. 1D and supplemental Video 1), thrombus formation was not observed. PubMed:19276082
In contrast, selectively removing RBCs prevented endothelial denudation and collagen exposure, resulting in a relatively mild perturbation of endothelial function similar to that observed with FeCl3 alone (data not shown). PubMed:19276082
Topical treatment with 6% FeCl3 with hemin (1mM) perfusions caused no greater endothelial injury than FeCl3 or hemin (1 mM) alone (data not shown), whereas FeCl3 in the presence of low concentrations of metHb (0.38 mg/ml) induced extensive vascular injury similar to that observed with FeCl3 in the presence of whole blood (Figs. 4 and 1D, respectively). PubMed:19276082
Third, reintroduction of washed RBCs or purified metHb in the presence of FeCl3 led to a similar level of vascular injury as observed with whole blood, whereas isolated RBC membranes and heme, even in the presence of FeCl3, produced relatively mild injury. PubMed:19276082
As shown in Fig 3B, lipids from atherosclerotic lesions were cytotoxic to endothelium, an effect strikingly enhanced when lipids were pre-oxidized by exposure to heme. PubMed:20378845
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.