Progesterone protects endothelial cells after cerebrovascular occlusion by decreasing MCP-1- and CXCL1-mediated macrophage infiltration

The biological role of macrophage infiltration into adipose tissue in obesity remains to be fully understood. We hypothesize that macrophages may act to stimulate angiogenesis in the adipose tissue. This possibility was examined by determining macrophage expression of angiogenic factor PDGF (platelet-derived growth factor) and regulation of tube formation of endothelial cells by PDGF. The data suggest that endothelial cell density was reduced in the adipose tissue of ob/ob mice. Expression of endothelial marker CD31 was decreased in protein and mRNA. The reduction was associated with an increase in macrophage infiltration. In the obese mice, PDGF concentration was elevated in the plasma, and its mRNA expression was increased in adipose tissue. Macrophages were found to be a major source of PDGF in adipose tissue, as deletion of macrophages led to a significant reduction in PDGF mRNA. In cell culture, PDGF expression was induced by hypoxia, and tube formation of endothelial cells was induced by PDGF. The PDGF activity was dependent on S6K, as inhibition of S6K in endothelial cells led to inhibition of the PDGF activity. We conclude that, in response to the reduced vascular density, macrophages may express PDGF in adipose tissue to facilitate capillary formation in obesity. Although the PDGF level is elevated in adipose tissue, its activity in angiogenesis is dependent on the availability of sufficient endothelial cells. The study suggests a new function of macrophages in the adipose tissue in obesity.

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Isoform-Specific Roles of ERK1 and ERK2 in Arteriogenesis

Cells ◽

10.3390/cells9010038 ◽

2019 ◽

Vol 9 (1) ◽

pp. 38 ◽

Cited By ~ 6

Author(s):

Nicolas Ricard ◽

Jiasheng Zhang ◽

Zhen W. Zhuang ◽

Michael Simons

Keyword(s):

Endothelial Cells ◽

Intracellular Signaling ◽

Clinical Importance ◽

Macrophage Infiltration ◽

Endothelial Cell Proliferation ◽

Vascular Endothelial ◽

Ischemic Event ◽

Intracellular Signaling Pathway ◽

First Time

Despite the clinical importance of arteriogenesis, this biological process is poorly understood. ERK1 and ERK2 are key components of a major intracellular signaling pathway activated by vascular endothelial growth (VEGF) and FGF2, growth factors critical to arteriogenesis. To investigate the specific role of each ERK isoform in arteriogenesis, we used mice with a global Erk1 knockout as well as Erk1 and Erk2 floxed mice to delete Erk1 or Erk2 in endothelial cells, macrophages, and smooth muscle cells. We found that ERK1 controls macrophage infiltration following an ischemic event. Loss of ERK1 in endothelial cells and macrophages induced an excessive macrophage infiltration leading to an increased but poorly functional arteriogenesis. Loss of ERK2 in endothelial cells leads to a decreased arteriogenesis due to decreased endothelial cell proliferation and a reduced eNOS expression. These findings show for the first time that isoform-specific roles of ERK1 and ERK2 in the control of arteriogenesis.

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Endothelial ADAM17 Expression in the Progression of Kidney Injury in an Obese Mouse Model of Pre-Diabetes

International Journal of Molecular Sciences ◽

10.3390/ijms23010221 ◽

2021 ◽

Vol 23 (1) ◽

pp. 221

Author(s):

Vanesa Palau ◽

Josué Jarrín ◽

Sofia Villanueva ◽

David Benito ◽

Eva Márquez ◽

...

Keyword(s):

Endothelial Cells ◽

Mouse Model ◽

High Fat Diet ◽

Macrophage Infiltration ◽

Creatinine Ratio ◽

Wild Type ◽

High Fat ◽

Tnf Α ◽

Galectin 3 ◽

Factor Α

Disintegrin and metalloproteinase domain 17 (ADAM17) activates inflammatory and fibrotic processes through the shedding of various molecules such as Tumor Necrosis Factor-α (TNF-α) or Transforming Growht Factor-α (TGF-α). There is a well-recognised link between TNF-α, obesity, inflammation, and diabetes. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium. The aim of this study was to characterize, for the first time, an experimental mouse model fed a high-fat diet (HFD) with a specific deletion of Adam17 in endothelial cells and to analyse the effects on different renal structures. Endothelial Adam17 knockout male mice and their controls were fed a high-fat diet, to induce obesity, or standard rodent chow, for 22 weeks. Glucose tolerance, urinary albumin-to-creatinine ratio, renal histology, macrophage infiltration, and galectin-3 levels were evaluated. Results showed that obese mice presented higher blood glucose levels, dysregulated glucose homeostasis, and higher body weight compared to control mice. In addition, obese wild-type mice presented an increased albumin-to-creatinine ratio; greater glomerular size and mesangial matrix expansion; and tubular fibrosis with increased galectin-3 expression. Adam17 deletion decreased the albumin-to-creatinine ratio, glomerular mesangial index, and tubular galectin-3 expression. Moreover, macrophage infiltration in the glomeruli of obese Adam17 knockout mice was reduced as compared to obese wild-type mice. In conclusion, the expression of ADAM17 in endothelial cells impacted renal inflammation, modulating the renal function and histology in an obese pre-diabetic mouse model.

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Abstract 3917: Role of Endothelial Cell-Selective Adhesion Molecule in the Progression of Atherosclerosis

Circulation ◽

10.1161/circ.118.suppl_18.s_502-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Michihiko Inoue ◽

Tatsuro Ishida ◽

Tetsuya Hara ◽

Cangara M Husni ◽

Li Sun ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Adhesion Molecule ◽

Lesion Size ◽

Macrophage Infiltration ◽

Immunoglobulin Superfamily ◽

Double Knockout ◽

Aortic Sinus

Backgrounds : Endothelial cell-selective adhesion molecule (ESAM) is a new member of the immunoglobulin superfamily, which is expressed in vascular endothelial cells. Although ESAM has been shown to mediate homohilic adhesion between endothelial cells, the interaction of ESAM and hematopoietic cells has not been ingestigated. Also, the role of ESAM in atherosclerosis remains unclear. In this study, we assessed the role of ESAM in monocyte/ macarophage infiltration, and examined effects of ESAM inactivation in the development atherosclerosis using a murine model of atherosclerosis. Methods and Results : ESAM−/− mice were bred with apoE−/− mice to generate the double knockout mice, and the lesion size of aortic sinus was evaluated histologically between ESAM+/+ apoE−/− and ESAM−/− apoE+/+ mice. Plasma lipid profile was not affected by ESAM deficiency. However, the lesion size was markedly attenuated in ESAM−/− apoE−/− mice compared to ESAM+/+apoE−/− mice. The percentage of MOMA-2-stained area in the aortic sinus lesions was significantly smaller in ESAM-/-apoE−/− mice than in ESAM+/+apoE−/− mice, suggesting that ESAM deficiency reduced the macrophage infiltration in the atheroma. To clarify the mechanism for the reduced macrophage content in the plaque, in vitro adhesion- and transendothelial migration assays were performed between cultured endothelial monolayers and monocyte/macrophage cell line THP-1 cells utilizing siRNA-mediated knockdown of ESAM. These assays revealed that ESAM deficiency in endothelial cells resulted in decreases in monocyte adhesion to the endothelial cells as well as transendothelialmigration. THP-1 cells did not express ESAM, but directly bound to the recommbinant ESAM protein-coated culture plates. Conclusion : ESAM modulates macrophage infiltration into the atheroma through interaction with unidentified ligand(s) on monocytes. ESAM inactivation can reduce susceptibility to atherosclerosis.

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Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100050755 ◽

1974 ◽

Vol 32 ◽

pp. 148-149

Author(s):

D. E. Philpott ◽

A. Takahashi

Keyword(s):

Skeletal Muscle ◽

Endothelial Cells ◽

Salivary Gland ◽

Carotid Artery ◽

Basement Membrane ◽

Coronary Vessels ◽

Ruthenium Red ◽

E Coli ◽

Old Rats ◽

The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

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Complex Vesicles, Microtubules, and Cytoplasmic Filaments in the Endothelial Cells of Normal Dog Aorta

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100603 ◽

1968 ◽

Vol 26 ◽

pp. 172-173

Author(s):

C. N. Sun ◽

J. J. Ghidoni

Keyword(s):

Electron Microscopy ◽

Endothelial Cells ◽

Cross Sections ◽

Functional Significance ◽

Tubular Structures ◽

Aldehyde Fixation ◽

Cytoplasmic Filaments

Endothelial cells in longitudinal and cross sections of aortas from 3 randomly selected “normal” mongrel dogs were studied by electron microscopy. Segments of aorta were distended with cold cacodylate buffered 5% glutaraldehyde for 10 minutes prior to being cut into small, well oriented tissue blocks. After an additional 1-1/2 hour period in glutaraldehyde, the tissue blocks were well rinsed in buffer and post-fixed in OsO4. After dehydration they were embedded in a mixture of Maraglas, D.E.R. 732, and DDSA.Aldehyde fixation preserves the filamentous and tubular structures (300 Å and less) for adequate demonstration and study. The functional significance of filaments and microtubules has been recently discussed by Buckley and Porter; the precise roles of these cytoplasmic components remains problematic. Endothelial cells in canine aortas contained an abundance of both types of structures.

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Ultrastructural Alterations in Sinusoidal Endothelial Fenestrae as a Result of Hypoxia

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100090828 ◽

1976 ◽

Vol 34 ◽

pp. 168-169

Author(s):

Waykin Nopanitaya ◽

Raeford E. Brown ◽

Joe W. Grisham ◽

Johnny L. Carson

Keyword(s):

Endothelial Cells ◽

Experimental Model ◽

Hepatic Lobule ◽

Ultrastructural Alterations ◽

Large Type ◽

Sinusoidal Endothelial Fenestrae ◽

General Size ◽

Sem Studies

Mammalian endothelial cells lining hepatic sinusoids have been found to be widely fenestrated. Previous SEM studies (1,2) have noted two general size catagories of fenestrations; large fenestrae were distributed randomly while the small type occurred in groups. These investigations also reported that large fenestrae were more numerous and larger in the endothelial cells at the afferent ends of sinusoids or around the portal areas, whereas small fenestrae were more numerous around the centrilobular portion of the hepatic lobule. It has been further suggested that under some physiologic conditions small fenestrae could fuse and subsequently become the large type, but this is, as yet, unproven.We have used a reproducible experimental model of hypoxia to study the ultrastructural alterations in sinusoidal endothelial fenestrations in order to investigate the origin of occurrence of large fenestrae.

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Ultrastructural studies on the interaction of haemophilus influenzae with human endothelial cells in vitro

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010016073x ◽

1990 ◽

Vol 48 (3) ◽

pp. 636-637

Author(s):

D.J.P. Ferguson ◽

M. Virji ◽

H. Kayhty ◽

E.R. Moxon

Keyword(s):

Endothelial Cells ◽

Haemophilus Influenzae ◽

Intercellular Junctions ◽

Blood Stream ◽

Ultrastructural Studies ◽

Endothelial Barriers ◽

Serotype B ◽

Meningitis In Children ◽

Respiratory Epithelial

Haemophilus influenzae is a human pathogen which causes meningitis in children. Systemic H. influenzae infection is largely confined to encapsulated serotype b organisms and is a major cause of meningitis in the U.K. and elsewhere. However, the pathogenesis of the disease is still poorly understood. Studies in the infant rat model, in which intranasal challenge results in bacteraemia, have shown that H. influenzae enters submucosal tissues and disseminates to the blood stream within minutes. The rapidity of these events suggests that H. influenzae penetrates both respiratory epithelial and endothelial barriers with great efficiency. It is not known whether the bacteria penetrate via the intercellular junctions, are translocated within the cells or carried across the cellular barrier in 'trojan horse' fashion within phagocytes. In the present studies, we have challenged cultured human umbilical cord_vein endothelial cells (HUVECs) with both capsulated (b+) and capsule-deficient (b-) isogenic variants of one strain of H. influenzae in order to investigate the interaction between the bacteria and HUVEC and the effect of the capsule.

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