Acute Exposure of Collecting Lymphatic Vessels to Low-Density Lipoproteins Increases Both Contraction Frequency and Lymph Flow: An In Vivo Mechanical Insight

2020 ◽  
Vol 18 (2) ◽  
pp. 146-155 ◽  
Author(s):  
Eleonora Solari ◽  
Cristiana Marcozzi ◽  
Barbara Bartolini ◽  
Manuela Viola ◽  
Daniela Negrini ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Low Density Lipoproteins ◽  
Lymph Flow ◽  
Acute Exposure ◽  
Low Density ◽  
Contraction Frequency

scholarly journals Mesenteric lymph flow in adult and aged rats

2011 ◽  
Vol 301 (5) ◽  
pp. H1828-H1840 ◽  
Author(s):  
Tony J. Akl ◽  
Takashi Nagai ◽  
Gerard L. Coté ◽  
Anatoliy A. Gashev
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
Contraction Frequency ◽  
Stress Load ◽  
Wall Shear ◽  
Contractile Characteristics

The objective of study was to evaluate the aging-associated changes, contractile characteristics of mesenteric lymphatic vessels (MLV), and lymph flow in vivo in male 9- and 24-mo-old Fischer-344 rats. Lymphatic diameter, contraction amplitude, contraction frequency, and fractional pump flow, lymph flow velocity, wall shear stress, and minute active wall shear stress load were determined in MLV in vivo before and after Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) application at 100 μM. The active pumping of the aged rat MLV in vivo was found to be severely depleted, predominantly through the aging-associated decrease in lymphatic contractile frequency. Such changes correlate with enlargement of aged MLV, which experienced much lower minute active shear stress load than adult vessels. At the same time, pumping in aged MLV in vivo may be rapidly increased back to levels of adult vessels predominantly through the increase in contraction frequency induced by nitric oxide (NO) elimination. Findings support the idea that in aged tissues surrounding the aged MLV, the additional source of some yet unlinked lymphatic contraction-stimulatory metabolites is counterbalanced or blocked by NO release. The comparative analysis of the control data obtained from experiments with both adult and aged MLV in vivo and from isolated vessel-based studies clearly demonstrated that ex vivo isolated lymphatic vessels exhibit identical contractile characteristics to lymphatic vessels in vivo.

Effects of oxidized low-density lipoproteins on the hepatic microvasculature

2011 ◽  
Vol 301 (4) ◽  
pp. G684-G693 ◽  
Author(s):  
Ana Oteiza ◽  
Ruomei Li ◽  
Robert S. McCuskey ◽  
Bård Smedsrød ◽  
Karen Kristine Sørensen
Keyword(s):  
Electron Microscopy ◽  
Linear Trend ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
Intercellular Adhesion Molecule ◽  
Organ Distribution ◽  
Low Density ◽  
Hepatic Microcirculation ◽  
Oxidized Low Density Lipoproteins

Oxidized low-density lipoproteins (oxLDLs) are involved in proinflammatory and cytotoxic events in different microcirculatory systems. The liver is an important scavenger organ for circulating oxLDLs. However, the interaction of oxLDL with the hepatic microcirculation has been poorly investigated. The present study was conducted to examine the effects of differently modified oxLDLs on the hepatic microvasculature. C57Bl/6J mice were injected intravenously with low-density lipoprotein (LDL), or LDL oxidized for 3 h (oxLDL3) or 24 h (oxLDL24), at doses resembling oxLDL plasma levels in cardiovascular disease patients. Radioiodinated ligands were used to measure blood decay and organ distribution, and nonlabeled ligands to evaluate microcirculatory responses, examined by in vivo microscopy 30–60 min after ligand injection, immunohistochemistry, and scanning and transmission electron microscopy. Mildly oxLDL (oxLDL3) was cleared from blood at a markedly slower rate than heavily oxLDL (oxLDL24), but significantly faster than LDL ( P < 0.01). Injected oxLDLs distributed to liver. OxLDL effects were most pronounced in central areas of the liver lobules where oxLDL3elicited a significant ( P < 0.05) reduction in perfused sinusoids, and both oxLDL3and oxLDL24significantly increased the numbers of swollen endothelial cells and adherent leukocytes compared with LDL ( P < 0.05). OxLDL-treated livers also exhibited increased intercellular adhesion molecule (ICAM)-1 centrilobular staining. Electron microscopy showed a 30% increased thickness of the liver sinusoidal endothelium in the oxLDL3group ( P < 0.05) and a reduced sinusoidal fenestration in centrilobular areas with increased oxidation of LDL ( P for linear trend <0.05). In conclusion, OxLDL induced several acute changes in the liver microvasculature, which may lead to sinusoidal endothelial dysfunction.

scholarly journals Antioxidant and Protective Effects of Artemisia campestris Essential Oil Against Chlorpyrifos-Induced Kidney and Liver Injuries in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Mongi Saoudi ◽  
Riadh Badraoui ◽  
Fatma Rahmouni ◽  
Kamel Jamoussi ◽  
Abdelfattah El Feki
Keyword(s):  
Essential Oil ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Protective Effects ◽  
Liver Injuries ◽  
Liver And Kidney ◽  
Artemisia Campestris ◽  
Morphologic Changes ◽  
Histopathologic Features

This study is aimed to elucidate the possible antioxidant and protective effects of Artemisia campestris essential oil (ACEO) against the deleterious effects of chlorpyrifos (CPF) in rats. The in vivo study revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activities and the serum contents of creatinine, urea, uric acid, cholesterol, triglycerides, low density lipoproteins (LDL), and glucose in rats treated with CPF as compared to controls. Meanwhile, hepatic and renal activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in liver and kidney decreased and the content of malondialdehyde (MDA) increased. Some histopathologic features were noticed in liver and kidney of the CPF group. Interestingly, ACEO alleviated the biochemical disruptions and reduced these hepato-renal morphologic changes.

scholarly journals Macrophages Create an Acidic Extracellular Hydrolytic Compartment to Digest Aggregated Lipoproteins

2009 ◽  
Vol 20 (23) ◽  
pp. 4932-4940 ◽  
Author(s):  
Abigail S. Haka ◽  
Inna Grosheva ◽  
Ethan Chiang ◽  
Adina R. Buxbaum ◽  
Barbara A. Baird ◽  
...  
Keyword(s):  
Free Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
Critical Event ◽  
Low Density ◽  
Acid Hydrolases ◽  
Detailed Understanding ◽  
Physical Features

A critical event in atherogenesis is the interaction of macrophages with subendothelial lipoproteins. Although most studies model this interaction by incubating macrophages with monomeric lipoproteins, macrophages in vivo encounter lipoproteins that are aggregated. The physical features of the lipoproteins require distinctive mechanisms for their uptake. We show that macrophages create an extracellular, acidic, hydrolytic compartment to carry out digestion of aggregated low-density lipoproteins. We demonstrate delivery of lysosomal contents to these specialized compartments and their acidification by vacuolar ATPase, enabling aggregate catabolism by lysosomal acid hydrolases. We observe transient sealing of portions of the compartments, allowing formation of an “extracellular” proton gradient. An increase in free cholesterol is observed in aggregates contained in these compartments. Thus, cholesteryl ester hydrolysis can occur extracellularly in a specialized compartment, a lysosomal synapse, during the interaction of macrophages with aggregated low-density lipoprotein. A detailed understanding of these processes is essential for developing strategies to prevent atherosclerosis.

scholarly journals Aggregation and fusion of low-density lipoproteins in vivo and in vitro

2013 ◽  
Vol 4 (5) ◽  
pp. 501-518 ◽  
Author(s):  
Mengxiao Lu ◽  
Olga Gursky
Keyword(s):  
Lipid Droplet ◽  
Current Knowledge ◽  
Single Copy ◽  
Droplet Formation ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Atherosclerotic Lesions ◽  
Lipid Droplet Formation

AbstractLow-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions.

scholarly journals Phasic contractions of rat mesenteric lymphatics increase basal and phasic nitric oxide generation in vivo

2009 ◽  
Vol 297 (4) ◽  
pp. H1319-H1328 ◽  
Author(s):  
H. Glenn Bohlen ◽  
Wei Wang ◽  
Anatoliy Gashev ◽  
Olga Gasheva ◽  
Dave Zawieja
Keyword(s):  
Nitric Oxide ◽  
Relaxation Mechanism ◽  
Lymph Flow ◽  
Lymphatic Endothelium ◽  
Contraction Frequency ◽  
Diastolic Relaxation ◽  
Intravenous Saline ◽  
First Time

Multiple investigators have shown interdependence of lymphatic contractions on nitric oxide (NO) activity by pharmacological and traumatic suppression of endothelial NO synthase (eNOS). We demonstrated that lymphatic diastolic relaxation is particularly sensitive to NO from the lymphatic endothelium. The predicted mechanism is shear forces produced by the lymph flow during phasic pumping, activating eNOS in the lymphatic endothelium to produce NO. We measured [NO] during phasic contractions using microelectrodes on in situ mesenteric lymphatics in anesthetized rats under basal conditions and with an intravenous saline bolus (0.5 ml/100 g) or infusion (0.5 ml·100 g−1·h−1). Under basal conditions, [NO] measured on the tubular portions of the lymphatics was ∼200–250 nM, slightly higher than in the adjacent adipocyte microvasculature, whereas [NO] measured on the lymphatic bulb surface was ∼400 nM. Immunohistochemistry of eNOS in isolated lympathics indicated a much greater expression in the lymph valves and surrounding bulb area than in the tubular regions. During phasic lymphatic contractions, the valve and tubular [NO] increased with each contraction, and during intravenous saline infusion, [NO] increased in proportion to the contraction frequency and, presumably, lymph flow. The partial blockade of eNOS over ∼1 cm length with Nω-nitro-l-arginine methyl ester lowered the [NO]. These in vivo data document for the first time that both valvular and tubular lymphatic segments increase NO generation during each phasic contraction and that [NO] summated with increased contraction frequency. The combined data predict regional variations in eNOS and [NO] in the tubular and valve areas, plus the summated NO responses dependent on contraction frequency provide for a complex relaxation mechanism involving NO.

Probucol protects low-density lipoproteins from in vitro and in vivo oxidation

1994 ◽  
Vol 29 (4) ◽  
pp. 337-344 ◽  
Author(s):  
Gabriele Bittolo-Bon ◽  
Giuseppe Cazzolato ◽  
Pietro Avogaro
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density
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