The Vascular Endothelium

Davies, Mark G.; Hagen, Per-Otto

doi:10.1097/00000658-199321850-00003

Cited by 221 publications

(147 citation statements)

References 77 publications

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“…Weight, g 220 25 53 37 12 11 Anti-PECAM 11.1 Ϯ 2.1 18.8 Ϯ 2. times less than that in the lung (Crone, 1963;Davis and Hagen, 1993;Panes et al, 1995). After i.v.…”

Section: Organmentioning

confidence: 81%

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Platelet-Endothelial Cell Adhesion Molecule-1-Directed Immunotargeting to Cardiopulmonary Vasculature

Scherpereel¹,

Rome²,

Wiewrodt³

et al. 2002

J Pharmacol Exp Ther

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“…Weight, g 220 25 53 37 12 11 Anti-PECAM 11.1 Ϯ 2.1 18.8 Ϯ 2. times less than that in the lung (Crone, 1963;Davis and Hagen, 1993;Panes et al, 1995). After i.v.…”

Section: Organmentioning

confidence: 81%

“…In fact, roughly 30% of the total endothelium in the body belongs to the pulmonary vasculature (Davis and Hagen, 1993). Thus, even antibodies that do not discriminate between pulmonary and systemic endothelium (e.g., anti-PECAM) accumulate in the lungs after i.v.…”

mentioning

confidence: 99%

Platelet-Endothelial Cell Adhesion Molecule-1-Directed Immunotargeting to Cardiopulmonary Vasculature

Scherpereel¹,

Rome²,

Wiewrodt³

et al. 2002

J Pharmacol Exp Ther

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“…For a direct comparison of the predicted K a vs. σ s , we quantified endothelial targeting as a function of lung uptake of NCs in mice. Lung uptake is representative of endothelial targeting because the lung accounts for roughly 30% of the endothelium in vivo (35). Moreover, additional data (see Fig.…”

Section: Resultsmentioning

confidence: 98%

Computational model for nanocarrier binding to endothelium validated using in vivo, in vitro, and atomic force microscopy experiments

Liu

Weller²,

Zern

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

119

179

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A computational methodology based on Metropolis Monte Carlo (MC) and the weighted histogram analysis method (WHAM) has been developed to calculate the absolute binding free energy between functionalized nanocarriers (NC) and endothelial cell (EC) surfaces. The calculated NC binding free energy landscapes yield binding affinities that agree quantitatively when directly compared against analogous measurements of specific antibodycoated NCs (100 nm in diameter) to intracellular adhesion molecule-1 (ICAM-1) expressing EC surface in in vitro cell-culture experiments. The effect of antibody surface coverage (σ s ) of NC on binding simulations reveals a threshold σ s value below which the NC binding affinities reduce drastically and drop lower than that of single anti-ICAM-1 molecule to ICAM-1. The model suggests that the dominant effect of changing σ s around the threshold is through a change in multivalent interactions; however, the loss in translational and rotational entropies are also important. Consideration of shear flow and glycocalyx does not alter the computed threshold of antibody surface coverage. The computed trend describing the effect of σ s on NC binding agrees remarkably well with experimental results of in vivo targeting of the anti-ICAM-1 coated NCs to pulmonary endothelium in mice. Model results are further validated through close agreement between computed NC rupture-force distribution and measured values in atomic force microscopy (AFM) experiments. The three-way quantitative agreement with AFM, in vitro (cell-culture), and in vivo experiments establishes the mechanical, thermodynamic, and physiological consistency of our model. Hence, our computational protocol represents a quantitative and predictive approach for model-driven design and optimization of functionalized nanocarriers in targeted vascular drug delivery.absolute binding free energy | Monte Carlo | targeted drug delivery | multivalent interactions | antibody surface coverage T argeted delivery of functionalized nanocarriers (i.e., NCs coated with specific targeting ligands) to endothelium remains an important design challenge in pharmacological and biomedical sciences. The use of functionalized NCs offers a wide range of targeting options through tunable design parameters (size, shape, type, method of functionalization, etc.). This necessitates a multiparameter optimization for achieving efficacious targeting in drug delivery applications (1) including vascular-targeting in oncology (2-4).Rational design of functionalized NCs faces many challenges owing to the complexities of molecular and geometric parameters surrounding receptor-ligand interactions and NCs (5-9), lack of accurate characterization of hydrodynamic, physico-chemical barriers for NC uptake/arrest (10-14), and uncertainty in targeting environment in vivo (15)(16)(17).Among the factors impacting the design of NCs and therapeutic agents are: (i) binding affinity (18) Recently the binding affinity of functionalized NCs to ICAM-1 expressing EC surface has been studied experim...

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“…In prolonged duration of disease, a contributing factor may be the eventual reduction in SOD gene expression in diabetic rat aorta. 30) The free radical NO is derived from endothelium 31) and it is considered as vasodilator that participates in the general homeostasis of the vasculature. NO is a unstable radical and converted to nitrite/nitrate anion (NO -2 /NO -3 ) in a very short time which is more stable product.…”

Section: Discussionmentioning

confidence: 99%

Effect of <i>Lycium barbarum</i> Polysaccharide on the Improvement of Antioxidant Ability and DNA Damage in NIDDM Rats

Guo

Zhao

2006

YAKUGAKU ZASSHI

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The eŠects of polysaccharide extracted from Lycium barbarum (LBP) on blood glucose, oxidative stress and DNA damage in rats with non-insulin dependent diabetes mellitus (NIDDM) were studied. The results show that LBP treatment (10 mg/kg･d) for 4 weeks led to decreased levels of blood glucose, malondialdehyde (MDA) and nitric oxide (NO) in serum of fasting rats; and to increased serum level of superoxidedismutase (SOD). Furthermore, LBP could reduce cellular DNA damage in peripheral lymphocytes of NIDDM rats. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantiˆed by measuring tail length and tail moment. These results suggest that LBP can control blood glucose and modulate the metabolism of glucose, leading to signiˆcant improvement of oxidative stress markers (SOD, MDA) in rats with NIDDM. And that, LBP decreases DNA damage possibly via a decrease in oxidative stress levels. In conclusion, LBP as a dietary supplement may prevent the development of complications or even tendency to carcinogenesis in NIDDM rats.

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The Vascular Endothelium

Cited by 221 publications

References 77 publications

Platelet-Endothelial Cell Adhesion Molecule-1-Directed Immunotargeting to Cardiopulmonary Vasculature

Platelet-Endothelial Cell Adhesion Molecule-1-Directed Immunotargeting to Cardiopulmonary Vasculature

Computational model for nanocarrier binding to endothelium validated using in vivo, in vitro, and atomic force microscopy experiments

Effect of <i>Lycium barbarum</i> Polysaccharide on the Improvement of Antioxidant Ability and DNA Damage in NIDDM Rats

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