Effect of cell turnover and leaky junctions on arterial macromolecular transport

1985 ◽  
Vol 248 (6) ◽  
pp. H945-H960 ◽  
Author(s):  
S. Weinbaum ◽  
G. Tzeghai ◽  
P. Ganatos ◽  
R. Pfeffer ◽  
S. Chien
Keyword(s):  
Endothelial Permeability ◽  
Molecular Size ◽  
Quantitative Model ◽  
Cell Turnover ◽  
Local Enhancement ◽  
Macromolecular Transport ◽  
Face Area ◽  
Endothelial Surface ◽  
En Face ◽  
Intercellular Clefts

A new quantitative model is presented to explore the changes in vascular permeability that would result if the intercellular clefts around widely scattered endothelial cells were to become leaky to macromolecules in the range of roughly 4–10 nm during normal cell turnover. Although these open junctions occupy less than 10(-5) of the en face area of the endothelial surface, it is shown that the endothelial permeability can increase by 50–100% due to the experimentally observed regional variations in turnover in the larger arteries, whereas in the thinner walled veins and smaller arteries the subendothelial concentration is not significantly elevated. These results provide a very plausible explanation for the observed focal differences in the uptake of 125I-albumin and 131I-fibrinogen in blue and white areas and the nonselectivity of the local enhancement in uptake for these two molecules as a function of molecular size. The model has important implications for the localization of atherogenesis and the importance of endothelial cell turnover on the transport of proteins in vessels of all sizes.

Age-related changes in endothelial permeability and distribution volume of albumin in rat aorta

1993 ◽  
Vol 264 (3) ◽  
pp. H679-H685 ◽  
Author(s):  
J. Belmin ◽  
B. Corman ◽  
R. Merval ◽  
A. Tedgui
Keyword(s):  
Arterial Wall ◽  
Relative Concentration ◽  
Endothelial Permeability ◽  
Distribution Volume ◽  
Albumin Concentration ◽  
Macromolecular Transport ◽  
Age Related ◽  
The Media ◽  
Old Rats ◽  
Age Related Changes

Age-related changes in macromolecular transport across the arterial wall were investigated in 10-, 20-, and 30-mo-old WAG/Rij rats. Animals were injected with 125I- and 131I-labeled albumin, 90 and 5 min before they were killed, respectively. The transmural distribution of relative concentration of tracers in the aortic wall was obtained using en face serial sectioning technique. The apparent endothelial permeability to albumin calculated from the distribution of 5-min 131I-labeled albumin concentrations was significantly enhanced in 20- and 30-mo-old rats compared with 10-mo-old rats. The apparent distribution volume of albumin within the media, estimated as the mean medial 125I-labeled albumin concentration, was not significantly changed in 20-mo-old rats but was significantly decreased in the 30-mo-old animals. These age-related changes in the macromolecular transport suggest that the entry of plasma macromolecules in the aged arterial wall might be enhanced, whereas the efflux through the media may be impeded, possibly contributing to their trapping in the subendothelium.

Estrogens modulate bovine vascular endothelial cell permeability and HSP 25 expression concomitantly

1998 ◽  
Vol 275 (3) ◽  
pp. H1011-H1015 ◽  
Author(s):  
F. Delarue ◽  
S. Daunes ◽  
R. Elhage ◽  
A. Garcia ◽  
F. Bayard ◽  
...  
Keyword(s):  
Vascular Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Vascular Endothelial Cell ◽  
Density Lipoprotein ◽  
Endothelial Permeability ◽  
Fluid Phase ◽  
Cell Permeability ◽  
Vascular Endothelial ◽  
Macromolecular Transport

The atheroprotective properties of estrogens are supported by clinical data from postmenopausal women who use estrogen replacement therapy. However, the mechanisms mediating activity remain unknown, and it has been suggested that estrogens may help to modulate endothelial permeability to atherogenic lipoproteins. In these studies we used bovine vascular endothelial cells as an in vitro model to show that estrogens were able to regulate low-density lipoprotein transport and permeability of the endothelial monolayer. Macromolecular transport was observed to be a second-order polynomial function of estrogen concentration. Moreover, this regulation was correlated with expression of heat shock protein (HSP) 25, which is known to influence fluid phase pinocytosis and cytoskeleton remodeling, thus suggesting a role for HSP 25 in the estrogenic control of transcellular permeability of the endothelium monolayer.

Permeability of Cortical Bone to Large Molecular Weight Proteins Under Diffusive and Load-Induced Convective Transport Mechanisms

2004 ◽  
Author(s):  
R. B. Patel ◽  
A. E. Tami ◽  
M. L. Knothe Tate
Keyword(s):  
Molecular Weight ◽  
Fluid Flow ◽  
Cortical Bone ◽  
Molecular Size ◽  
Convective Transport ◽  
Transport Mechanisms ◽  
Quantitative Evidence ◽  
Macromolecular Transport ◽  
Large Molecular Weight ◽  
Poroelasticity Theory

The composition of bone is 75% mineral and organic components and 25% fluid; yet until the past 30 years, the fluid component of bone had been ignored [1]. The idea of load induced fluid flow via pressure gradients was hypothesized for the first time by Piekarski et al in his application of Biot’s poroelasticity theory [2]. Poroelasticity theory mathematically describes the sponge-like behavior of bone: when bone is squeezed(loaded) fluid will be induced to flow. However although the concept of load induced fluid flow is well accepted in the orhopedic field, our study is the first to provide quantitative evidence of the effect of load induced fluid on macromolecular transport. Hence the goals of this study include observing permeability of large molecular weight tracers in cortical bone, ii.) comparing molecular size dependence on tracer permeability in cortical bone, and iii.) comparing effects of convective and diffusive transport mechanisms on permeability.

scholarly journals Effects of Atelocollagen Formulation Containing Oligonucleotide on Endothelial Permeability

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Koji Hanai ◽  
Takashi Kojima ◽  
Mika Ota ◽  
Jun Onodera ◽  
Norimasa Sawada
Keyword(s):  
Drug Delivery ◽  
Size Structure ◽  
Biological Effects ◽  
Adherens Junction ◽  
Endothelial Permeability ◽  
Molecular Size ◽  
P38 Map Kinase ◽  
Delivery Technology ◽  
Junction Proteins

Atelocollagen is a major animal protein that is used as a highly biocompatible biomaterial. To date, atelocollagen has been used as an effective drug delivery technology to sustain the release of antitumor proteins and to enhance the antitumor activity of oligonucleotides in in vivo models. However, the biological effects of this technology are not fully understood. In the present study, we investigated the effects of atelocollagen on endothelial paracellular barrier function. An atelocollagen formulation containing oligonucleotides specifically increased the permeability of two types of endothelial cells, and the change was dependent on the molecular size, structure of the oligonucleotides used and the concentrations of the oligonucleotide and atelocollagen in the formulation. An immunohistochemical examination revealed that the formulation had effects on the cellular skeleton and intercellular structure although it did not affect the expression of adherens junction or tight junction proteins. These changes were induced through p38 MAP kinase signaling. It is important to elucidate the biological functions of atelocollagen in order to be able to exploit its drug delivery properties.

Capillary endothelial morphometric profiles in fast and slow twitch muscle: alterations in response to anesthesia and electrical stimulation

1989 ◽  
Vol 47 ◽  
pp. 926-927
Author(s):  
T.G. Manfredi ◽  
D.W. Edington
Keyword(s):  
Electrical Stimulation ◽  
Endothelial Function ◽  
Cell Biology ◽  
Endothelial Permeability ◽  
Capillary Endothelium ◽  
Endothelial Surface ◽  
Slow Twitch Muscle ◽  
Slow Twitch ◽  
Lung Capillaries ◽  
Fast Twitch

Recent investigations focusing on transcapillary exchange have correlated physiologic and ultrastructural findings in an effort to understand mechanisms associated with endothelial function. The vascular endothelium is permeable to water and macromolecules such as lipoproteins and plasma proteins. Plasmalemmal vesicles inside the endothelium are involved with the transport of substances. These vesicles can fuse on both endothelial fronts and they can form transendothelial channels by way of vesicular fusion. These ultrastructural alterations can increase the capillary endothelial surface area by a factor of 0.5-2.0. Recent studies suggest that endothelial permeability is modulated by the fusion of vesicles into clusters which may act as transendothelial channels. The density of vesicles differ from one tissue to another. Vesicle numbers are under physiologic control and have been reported to increase in lung capillaries in response to edema and hydrostatic pressure. Physiology and cell biology must be integrated in an effort to understand the complexity of endothelial function. Therefore, the purpose of this study was to compare the morphometric profiles of capillary endothelium response to anesthesia and electrical stimulation in two muscles of the rat hind limb, the capillary enriched slow-twitch soleus, and the low oxidative fast-twitch plantaris.

Abstract 2: Aorta Intima-Resident Macrophages Contribute to Atherosclerotic Lesion Initiation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jesse W Williams ◽  
Brian T Saunders ◽  
Ki-Wook Kim ◽  
Slava Epelman ◽  
Kory Lavine ◽  
...  
Keyword(s):  
Atherosclerotic Lesion ◽  
Kinetic Studies ◽  
Endothelial Damage ◽  
Lineage Tracing ◽  
Cellular Mechanisms ◽  
Gm Csf ◽  
Endothelial Surface ◽  
En Face ◽  
Aortic Intima

Atherosclerosis is an underlying cause of cardiovascular disease and a leading cause of mortality worldwide. Macrophage accumulation in atherosclerotic plaque, their uptake of cholesterol, and subsequent local death drive disease progression. Lipid-laden plaque macrophages are thought to be exclusively derived from blood monocyte progenitors that are recruited following endothelial damage induced by cholesterol exposure. In our current study, we focused on characterization of resident vascular macrophages that reside in the aortic intima in plaque-prone areas, previously identified as ‘vascular dendritic cells’. Using en face whole-mount confocal microscopy of aortas, we confirm a uniform resident CD64 + CD11c + CX3CR1 + MHCII + macrophage population, which is present in C57/BL6 mice resistant to atherosclerosis. Importantly, they do not express dendritic cell restricted genes zBTB46 or L-myc. We find aortic macrophages require M-CSF and Flt3 signaling for survival, but are independent of CCR2, CCR7, and GM-CSF receptor signaling, making them a distinct myeloid population. Lineage-tracing and parabiosis approaches suggest these cells derive from definitive hematopoiesis and are then self-maintained independent of blood-progenitors. Using these characterization data, we developed a labeling strategy to identify resident from recruited macrophages during kinetic studies of lesion progression. We find that resident aortic macrophages are the first cells to take up lipid following high fat diet exposure and expand within the arterial wall to form the initial lesion bed. In the absence of resident macrophages early lipid deposition in the aortic arch is ablated. Finally, utilizing an intravital carotid artery imaging approach, we identify resident aortic macrophages to be potential mediators of monocyte recruitment through direct interactions with rolling monocytes on the endothelial surface under diseased and steady-states. Overall, these results shift our understanding of the cellular mechanisms responsible for plaque construction and maintenance.

Permeability of neutral vs. anionic dextrans in cultured brain microvascular endothelium

1990 ◽  
Vol 259 (1) ◽  
pp. H162-H166 ◽  
Author(s):  
G. Sahagun ◽  
S. A. Moore ◽  
M. N. Hart
Keyword(s):  
Endothelial Cells ◽  
Endothelial Permeability ◽  
Cell Permeability ◽  
Microvascular Endothelium ◽  
Endothelial Surface ◽  
Luminal Side ◽  
Brain Microvessel ◽  
Relationship Of ◽  
The Relationship

The luminal surface of vascular endothelium contains glycocalyx residues that establish an overall negative charge. Recent evidence has suggested that local endothelial surface charge properties may account for the permeability properties of various macromolecules. It has also been suggested that altered membrane charge on the luminal side may play a role in thrombogenesis and atherogenesis. The relationship of macromolecule charge to endothelial cell permeability was examined in vitro using mouse brain microvessel endothelial cells grown to confluence on a nitrocellulose filter separating a double-chamber system. Endothelial permeability to 4K and 10K fluorescein-labeled neutral dextrans was compared with the permeability to 4K and 10K fluorescein-labeled anionic dextrans (sulfated). After 1 h, there was significantly greater permeability of neutral fluorescein-labeled dextran than of anionic fluorescein-labeled dextran in each particle size. In addition, there was significantly greater permeability of 4K than 10K fluorescein-labeled dextrans of either charge. The findings indicate that charge in addition to size plays an important role in the movement of macromolecules across cultured microvascular endothelial cells.

Macromolecular transport in heart valves. I. Studies of rat valves with horseradish peroxidase

2007 ◽  
Vol 292 (6) ◽  
pp. H2664-H2670 ◽  
Author(s):  
Zhongqing Zeng ◽  
Yongyi Yin ◽  
An-Li Huang ◽  
Kung-Ming Jan ◽  
David S. Rumschitzki
Keyword(s):  
Horseradish Peroxidase ◽  
Heart Valves ◽  
Molecular Diffusion ◽  
Structural Features ◽  
Sprague Dawley ◽  
Macromolecular Transport ◽  
Transmission Electron ◽  
Endothelial Surface ◽  
The Matrix ◽  
Subendothelial Space

The present study aims to experimentally elucidate subtle structural features of the rat valve leaflet and the related nature of macromolecular transport across its endothelium and in its subendothelial space, information necessary to construct a rational theoretical model that can explain observation. After intravenous injection of horseradish peroxidase (HRP), we perfusion-fixed the aortic valve of normal Sprague-Dawley rats and found under light microscopy that HRP leaked through the leaflet's endothelium at very few localized brown spots, rather than uniformly. These spots grew nearly as rapidly with HRP circulation time before euthanasia as aortic spots, particularly when the time axis only included the time the valve was closed. These results suggest that macromolecular transport in heart valves depends not only on the direction normal to, but also parallel to, the endothelial surface and that convection, as well as molecular diffusion, plays an important role in macromolecular transport in heart valves. Transmission electron microscopy of traverse leaflet sections after 4-min HRP circulation showed a very thin (∼150 nm), sparse layer immediately beneath the endothelium where the HRP concentration was much higher than that in the matrix below it. Nievelstein-Post et al.'s (Nievelstein-Post P, Mottino G, Fogelman A, Frank J. Arterioscler Thromb 14: 1151–1161, 1994) ultrarapid freezing/rotary shadow etching of the normal rabbit valve's subendothelial space supports the existence of this very thin, very sparse “valvular subendothelial intima,” in analogy to the vascular subendothelial intima.

Vascular injury by endotoxin: changes in macromolecular transport parameters in rat aortas in vivo

1992 ◽  
Vol 262 (5) ◽  
pp. H1563-H1571 ◽  
Author(s):  
M. S. Penn ◽  
G. M. Saidel ◽  
G. M. Chisolm
Keyword(s):  
Vascular Injury ◽  
Time Course ◽  
Endothelial Permeability ◽  
Effective Diffusivity ◽  
Rat Aorta ◽  
Transport Parameters ◽  
Internal Elastic Lamina ◽  
Maximum Increase ◽  
Macromolecular Transport

Vascular injury can lead to enhanced macromolecular transport into the arterial wall. We previously demonstrated that lipopolysaccharide (LPS) -induced injury to rat aorta in vivo caused increases in intimal and medial horseradish peroxidase (HRP) accumulation. In the present study, we quantitatively interpret these LPS-induced changes in HRP transport parameters. The parameters of interest are the permeability (PL) of the luminal blood-tissue boundary (combination of endothelium and internal elastic lamina, IEL), the effective diffusivity (D), and the convective velocity (V) across the media. The parameter values that yield the best fit of the model to the data provide a basis for understanding the tissue changes. The time of peak transmural (medial) accumulation (24 h after LPS injection) correlated with increases in PL (peak, 12-48 h) and preceded the maximum increase in V (peak, 36 h). The monotonic increase in the intimal accumulation during the 5 days after the injury has a time course distinct from the transient increases in PL and from the changes in D, which implies that endothelial permeability has only limited influence on transport beyond the intima. These data implicate the IEL as a barrier to macromolecular transport in the normal aorta and demonstrate that the endothelium and IEL work in concert to determine intimal macromolecular accumulation.

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