The microcirculation in atherogenesis

Lehr, H.-A.; Messmer, K.

doi:10.1016/s0008-6363(96)00164-2

Cited by 11 publications

(9 citation statements)

References 25 publications

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“…Since turnover rates of endothelial cells are rather low [30], the endothelium might represent a tissue where relevant accumulation of starch molecules could occur. Moreover, during shock syndromes and ischemia/reperfusion, endothelial cells represent an especially important site of the body where cell activation leads to adhesion molecule expression, leukocyte recruitment and ultimately results in leukocytemediated tissue injury [8][9][10][11]13]. In agreement with previous studies on short-term effects of HES on endothelial cell adhesion molecules [31,32], adhesion molecule ex-pression on cytokine-activated HUVEC was not affected by starch accumulation after long-term treatment in our experiment.…”

Section: Discussionsupporting

confidence: 92%

“…The endothelium, however, plays a central role in the pathogenesis of sepsis, shock or ischemia/reperfusion injury [7][8][9][10]. On endothelial cells, the expression of E-and P-selectin, ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) leads to a multistep process of leukocyte-endothelial interactions.…”

Section: Introductionmentioning

confidence: 99%

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Endothelial Accumulation of Hydroxyethyl Starch and Functional Consequences on Leukocyte-Endothelial Interactions

Nohé¹,

Burchard²,

Zanke³

et al. 2002

Eur Surg Res

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To date, accumulation of hydroxyethyl starch (HES) has been studied mainly in skin specimens, but there are no detailed reports available regarding starch accumulation in the endothelium. Because endothelial cells play an essential role during shock, we studied the accumulation of HES in human umbilical venous endothelial cells (HUVEC). HUVEC (n = 9) were incubated with a fluorescein-conjugated HES 200/0.5 (FITC-HES) at 0.5–20 mg/ml for 1–72 h. FITC-HES was internalized dose- and time-dependently by pinocytosis into secondary lysosomes. Asymptotic elimination curves showed that 50% of the formerly ingested molecules could not be eliminated. Despite accumulation, starch molecules did not attenuate the expression of E-selectin, ICAM-1 or VCAM-1 on TNF-α-activated HUVEC. However, apart from adhesion molecule expression, perfusion studies showed that HES reduced neutrophil adhesion by direct inhibition of integrin-mediated interactions.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Endothelial Accumulation of Hydroxyethyl Starch and Functional Consequences on Leukocyte-Endothelial Interactions

Nohé¹,

Burchard²,

Zanke³

et al. 2002

Eur Surg Res

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“…endothelial dysfunction; shear-dependent dilation; arteriolar heterogeneity; ApoE3-Leiden HYPERCHOLESTEROLEMIA is a primary risk factor for coronary artery disease. Although atherosclerosis itself is confined to larger sized arteries, vascular changes extend into the microcirculation (18,20,33). In patients and animal models, hypercholesterolemia and atherosclerosis have been generally associated with an endothelial dysfunction of the resistance vasculature, representing a diminished bioavailability of nitric oxide (NO) as reflected by an impaired agonist-induced endotheliumdependent flow increase (3,8).…”

mentioning

confidence: 99%

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

VanTeeffelen¹,

Constantinescu²,

Vink³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Hypercholesterolemia and atherosclerosis have been associated with changes in the microvasculature, in particular with endothelial dysfunction. In the present study, the impact of atherogenic conditions on arteriolar vasomotor control was determined. Arteriolar [second-order (2A) and third-order (3A) arterioles; diameter range: 9-37 microm] responses during reactive hyperemia (RH) were determined in cremaster muscle of anesthetized mice. C57Bl/6 mice on normal rodent chow were used as controls and high-fat/high-cholesterol (HFC)-fed C57Bl/6 and ApoE3-Leiden mice as hypercholesterolemic mice. The HFC diet resulted in time-dependent increases in plasma cholesterol and triglyceride concentrations (P < 0.001), which were more pronounced in ApoE3-Leiden mice (P < 0.001). In control mice, inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine (L-NNA) reduced baseline diameter from 17.9 +/- 1.2 to 15.9 +/- 1.3 microm (P < 0.05) and decreased the duration of RH [time to 50% (t50) of recovery: 23.3 +/- 3.6 vs. 12.5 +/- 1.3 s (P = 0.003)]. t50 was longer in 2A versus 3A arterioles (33 +/- 3 vs. 18 +/- 2 s, P < 0.001) and increased with wall shear rate at the beginning of RH in 2A arterioles only. Compared with control mice, RH duration was reduced in 2A arterioles of HFC mice (t50: 11 +/- 2 s, P < 0.001 vs. control) but not affected in 3A vessels. L-NNA did not affect baseline diameter in HFC mice and reduced t50 only in "slow" responders (t50 > or = 10 s). It is concluded that hypercholesterolemia results in an impairment of NO-mediated vasomotor control in 2A but not 3A arterioles during dynamic changes of perfusion like RH. 2A arterioles likely therefore represent the functional locus of endothelial dysfunction during atherogenic conditions.

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“…Inclusion of albumin and lowdensity lipoproteins into the subendothelial space forms part of the process of atherogenesis. Thus ESL dysfunction may contribute to the microvascular disease phenotype of atherosclerosis (4,23,24). An altered vascular permeability is one of the earliest detectable symptoms of several pathophysiological states, including atherosclerosis, diabetes, shock, and tumors.…”

mentioning

confidence: 99%

Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy

Haaren

vanBavel

Vink

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

131

104

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. Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy. Am J Physiol Heart Circ Physiol 285: H2848-H2856, 2003. First published August 7, 2003 10.1152/ajpheart.00117.2003.-Endothelial cells are covered by a surface layer of membraneassociated proteoglycans, glycosaminoglycans, glycoproteins, glycolipids, and associated plasma proteins. This layer may limit transendothelial solute transport. We determined dimension and transport properties of this endothelial surface layer (ESL) in isolated arteries. Rat mesenteric small arteries (diameter ϳ150 m) were isolated and cannulated with a double-barreled -pipette on the inlet side and a regular pipette on the outlet side. Dynamics and localization of intraarterial fluorescence by FITC-labeled dextrans (FITC-⌬s) and the endothelial membrane dye DiI were determined with confocal microscopy. Large FITC-⌬ (148 kDa) filled a core volume inside the arteries within 1 min but was excluded from a 2.6 Ϯ 0.5-m-wide region on the luminal side of the endothelium during 30 min of dye perfusion. Medium FITC-⌬ (50.7 kDa) slowly penetrated this ESL within 30 min but did not permeate into the arterial wall. Small FITC-⌬ (4.4 kDa) quickly passed the ESL and accumulated in the arterial wall. Prolonged luminal fluorochrome illumination with a bright mercury lamp destroyed the ϳ3-m exclusion zone for FITC-⌬148 within a few minutes. This study demonstrates the presence of a thick ESL that contributes to the permeability barrier to solutes. The layer is sensitive to phototoxic stress, and its damage could form an early event in atherosclerosis. vascular permeability; isolated artery; endothelial surface layer; confocal microscopy; glycocalyx ENDOTHELIAL CELLS (ECs) are covered by a surface layer of membrane-associated proteoglycans, glycosaminoglycans, glycoproteins, glycolipids, and associated plasma proteins, known as the endothelial surface layer (ESL) (30). The functional properties of the ESL have been extensively described only recently. Biochemical research elucidates receptor functions of glycosaminoglycans within the ESL and the binding patterns of proteins to heparan sulfates (8,31,34). Biodegradation of sialic acid, an important constituent of the ESL, by neuraminidase inhibits shear-induced nitric oxide production (12, 29). The role of the ESL in the control of vascular wall permeability has been addressed in experimental studies (1, 21, 38) on microvessels and in new theoretical transport models (18). Vascular permeability forms an important parameter in the regulation of water and solute exchange between the circulation and tissues (10, 26). It is important that the intrusion of certain macromolecules into the arterial wall is limited. Inclusion of albumin and lowdensity lipoproteins into the subendothelial space forms part of the process of atherogenesis. Thus ESL dysfunction may contribute to the microvascular disease phenotype of atherosclerosis (4, 23, 24). An altered vascular permeability is one of the earliest detectable symptoms...

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The microcirculation in atherogenesis

Cited by 11 publications

References 25 publications

Endothelial Accumulation of Hydroxyethyl Starch and Functional Consequences on Leukocyte-Endothelial Interactions

Endothelial Accumulation of Hydroxyethyl Starch and Functional Consequences on Leukocyte-Endothelial Interactions

Hypercholesterolemia impairs reactive hyperemic vasodilation of 2A but not 3A arterioles in mouse cremaster muscle

Localization of the permeability barrier to solutes in isolated arteries by confocal microscopy

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