scholarly journals Angiogenic signaling in the lungs of a metabolically suppressed hibernating mammal (Ictidomys tridecemlineatus)

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8116 ◽  
Author(s):  
Samantha M. Logan ◽  
Kenneth B. Storey
Keyword(s):  
Cell Function ◽  
Limited Resource ◽  
Soluble Receptors ◽  
Differential Protein Expression ◽  
Endothelial Cell Function ◽  
Protein Levels ◽  
Decoy Receptors ◽  
Vascular Stability ◽  
Protein Receptors ◽  
Cleavage Complex

To conserve energy in times of limited resource availability, particularly during cold winters, hibernators suppress even the most basic of physiologic processes. Breathing rates decrease from 40 breaths/minute to less than 1 breath/min as they decrease body temperature from 37 °C to ambient. Nevertheless, after months of hibernation, these incredible mammals emerge from torpor unscathed. This study was conducted to better understand the protective and possibly anti-inflammatory adaptations that hibernator lungs may use to prevent damage associated with entering and emerging from natural torpor. We postulated that the differential protein expression of soluble protein receptors (decoy receptors that sequester soluble ligands to inhibit signal transduction) would help identify inhibited inflammatory signaling pathways in metabolically suppressed lungs. Instead, the only two soluble receptors that responded to torpor were sVEGFR1 and sVEGFR2, two receptors whose full-length forms are bound by VEGF-A to regulate endothelial cell function and angiogenesis. Decreased sVEGFR1/2 correlated with increased total VEGFR2 protein levels. Maintained or increased levels of key γ-secretase subunits suggested that decreased sVEGFR1/2 protein levels were not due to decreased levels of intramembrane cleavage complex subunits. VEGF-A protein levels did not change, suggesting that hibernators may regulate VEGFR1/2 signaling at the level of the receptor instead of increasing relative ligand abundance. A panel of angiogenic factors used to identify biomarkers of angiogenesis showed a decrease in FGF-1 and an increase in BMP-9. Torpid lungs may use VEGF and BMP-9 signaling to balance angiogenesis and vascular stability, possibly through the activation of SMAD signaling for adaptive tissue remodeling.

Abstract 14736: Aquaporin 1 Modulates H 2 o 2 -mediated Endothelial Inflammaging

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Seyed Soheil Saeedi Saravi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Signaling Pathways ◽  
Cell Function ◽  
Immunofluorescence Assay ◽  
Endothelial Cell Function ◽  
Aquaporin 1 ◽  
Knock Down ◽  
Protein Levels

Background: Aquaporin 1 (AQP1), a key regulator of endothelial cell function, transports hydrogen peroxide (H 2 O 2 ) into the cells. H 2 O 2 -mediated inflammation has been implicated in endothelial dysfunction, yet specific roles of AQP1-mediated signaling pathways underlying age-dependent endothelial dysfunction remains incompletely understood. Methods: In these studies, we dissected AQP1-regulated inflammation modulation of eNOS signaling pathways in human aortic endothelial cells (HAEC) from passages 5 to 15 by exploiting siRNA approaches, live cell fluorescence imaging with genetically-encoded H 2 O 2 biosensor HyPer, biochemical and in vitro endothelial function assays. Results: We discovered that AQP1 expression remarkably increases in senescent HAEC (P.15) in association with significant increased SA-βgal activity compared to young cells (P.5). H 2 O 2 levels were increased in senescent cell cytosol revealed by fluorescence HyPer imaging. We found that senescence-associated increase in AQP1-mediated H 2 O 2 led to enhanced TNF-α, unlike HO-1, transcription (p<0.01). Moreover, immunofluorescence assay documented that AQP1 gene knock-down significantly ameliorated senescence-associated elevation of adhesion molecule ICAM-1. Immunoblot analyses demonstrated that increased AQP1 protein levels in senescent HAEC leads to significant increase in caveolin-1 phosphorylation (2-fold) and decreases in phosphorylation of AMPK (Thr172; 4-fold) and eNOS (Ser1177; 2-fold) compared to young ECs (for each, p<0.05, n>6). We discovered that AQP1 knock-down improved the reduced angiogenesis and wound healing capacity in association with eNOS down-regulation in senescent endothelial cells. Conclusion: These results establish that AQP1 plays a crucial role in the regulation of H 2 O 2 -mediated inflammation-associated endothelial senescence, and AQP1 deletion improves endothelial dysfunction by ameliorating ROS-modulated inflammaging.

scholarly journals The effect of varied exercise intensity on antioxidant function, and aortic endothelial cell function and serum lipids in a non-alcoholic fatty liver disease rats

2018 ◽  
Author(s):  
Ling Ruan ◽  
Smart Neil.A. ◽  
Fanghui Li
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Cell Function ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Alcoholic Fatty Liver ◽  
Endothelial Cell Function ◽  
Protein Levels ◽  
Alcoholic Fatty Liver Disease

AbstractExercise and diet may improve cardio-metabolic health in non-alcoholic fatty liver disease, but the optimal exercise prescription remains unclear. We aimed to compare the effects of diet and exercise at different intensities on antioxidant function, and aortic endothelial cell function and serum lipids in a non-alcoholic fatty liver disease rats. Fifty Sprague Dawley rats (180-220g) were randomly divided into two experimental groups and fed either standard rodent chow diet or a high-fat diet. After16 weeks, these animals that received the HFD were randomly separated into a high fat control group or three exercise training groups: HF and low intensity exercise, HF and moderate intensity exercise, HF and incremental intensity exercise, these experimental rats keep sedentary or training for the next 6 weeks. Markers of Aortic Oxidative stress were detected using assay kit. Immunohistochemical analysis was performed to determine the expression level of eNOS and ET-1. Lipid metabolism parameters were detected with an automatic analyzer. Exercise at different intensities improved lipid metabolism, enhanced anti-oxidation function, reduced MDA, increased NO, and improved the expression of eNOS and ET-1 protein levels. Decreased blood lipids were exhibited in all exercise groups. Notably, moderate intensity exercise demonstrated more effect on increasing GSH contents, and decreased the expression of ET-1 protein levels.

Abstract 105: 20-HETE: An Inducer of ACE in Human Microvascular Endothelial Cells (HMVEC).

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Victor Garcia ◽  
Jennifer Cheng ◽  
Yan Ding ◽  
Cheng-Chia Wu ◽  
John R Falck ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Function ◽  
Cell Function ◽  
Renin Angiotensin System ◽  
Endothelial Activation ◽  
Microvascular Endothelial Cells ◽  
Arachidonic Acid Metabolite ◽  
Endothelial Cell Function ◽  
Protein Levels ◽  
Microvascular Endothelial

20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 derived arachidonic acid metabolite, is manufactured in the microcirculation and shown to sensitize the smooth muscle to constrictor stimuli and cause endothelial activation and dysfunction. Increased vascular production of 20-HETE promotes hypertension that is dependent, in part, on the renin angiotensin system. Microarray analysis of endothelial cells treated with 20-HETE revealed a five-fold upregulation of angiotensin converting enzyme (ACE). In cultured human microvascular endothelial cells (HMVEC), 20-HETE (5 nM) induced ACE mRNA by 3.1-fold (± 0.16 p<0.05), increased ACE protein levels by 4.2-fold (±0.99 p<0.05) and ACE activity by 2-fold (±0.23 p<0.05). These effects were abrogated by co-treatment with 20-HEDE, a 20-HETE antagonist. 20-HETE induction of ACE mRNA was abolished by inhibitors of EGFR-tyrosine kinase, MAPK and IKKβ activation but was not affected by PKC inhibition. Moreover, transfection of cells with IKKβ siRNA prevented 20-HETE from inducing ACE mRNA. Collectively, theses results suggest a role for 20-HETE as a regulator of endothelial ACE. This regulatory activity impacts vascular function since downregulation of ACE in endothelial cells treated with siRNA exogenous 20-HETE from inhibiting NO synthesis and stimulating O 2 - production. This study demonstrates that induction of ACE expression and activity is critical to the actions of 20-HETE on endothelial cell function, further implicating the induction of ACE and activation of RAS as a key mechanism by which excessive production of 20-HETE within the vasculature leads to hypertension.

Do DPP-4 inhibitors improve endothelial cell function?

2017 ◽  
Vol 01 (01) ◽  
Author(s):  
Hiroshi Nomoto ◽  
Hideaki Miyoshi ◽  
Akinobu Nakamura ◽  
Tatsuya Atsumi ◽  
Naoki Manda ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Endothelial Cell Function

Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury

Circulation ◽  
1997 ◽  
Vol 96 (5) ◽  
pp. 1624-1630 ◽  
Author(s):  
C. Roger White ◽  
Jonathan Shelton ◽  
Shi-Juan Chen ◽  
Victor Darley-Usmar ◽  
Leslie Allen ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Experimental Model ◽  
Vascular Injury ◽  
Cell Function ◽  
Endothelial Cell Function

scholarly journals CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation

2009 ◽  
Vol 296 (3) ◽  
pp. H689-H697 ◽  
Author(s):  
Karen Y. Stokes ◽  
LeShanna Calahan ◽  
Candiss M. Hamric ◽  
Janice M. Russell ◽  
D. Neil Granger
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
Blood Cell ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Microvascular Dysfunction ◽  
Cd40 Ligand ◽  
Scid Mice ◽  
Endothelial Cell Function

Hypercholesterolemia is associated with phenotypic changes in endothelial cell function that lead to a proinflammatory and prothrombogenic state in different segments of the microvasculature. CD40 ligand (CD40L) and its receptor CD40 are ubiquitously expressed and mediate inflammatory responses and platelet activation. The objective of this study was to determine whether CD40/CD40L, in particular T-cell CD40L, contributes to microvascular dysfunction induced by hypercholesterolemia. Intravital microscopy was used to quantify blood cell adhesion in cremasteric postcapillary venules, endothelium-dependent vasodilation responses in arterioles, and microvascular oxidative stress in wild-type (WT) C57BL/6, CD40-deficient (−/−), CD40L−/−, or severe combined immune deficient (SCID) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 wk. WT-HC mice exhibited an exaggerated leukocyte and platelet recruitment in venules and impaired vasodilation responses in arterioles compared with ND counterparts. A deficiency of CD40, CD40L, or lymphocytes attenuated these responses to HC. The HC phenotype was rescued in CD40L−/− and SCID mice by a transfer of WT T cells. Bone marrow chimeras revealed roles for both vascular- and blood cell-derived CD40 and CD40L in the HC-induced vascular responses. Hypercholesterolemia induced an oxidative stress in both arterioles and venules of WT mice, which was abrogated by either CD40 or CD40L deficiency. The transfer of WT T cells into CD40L−/− mice restored the oxidative stress. These results implicate CD40/CD40L interactions between circulating cells and the vascular wall in both the arteriolar and venular dysfunction elicited by hypercholesterolemia and identify T-cell-associated CD40L as a key mediator of these responses.

scholarly journals Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Cell Function ◽  
Computational Techniques ◽  
Apical Surface ◽  
Cardiovascular Research ◽  
Endothelial Cell Function ◽  
Wall Shear

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.

scholarly journals Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

2017 ◽  
Vol 232 (1) ◽  
pp. R27-R44 ◽  
Author(s):  
D S Boeldt ◽  
I M Bird
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cell Function ◽  
Endothelial Cell Dysfunction ◽  
Hypertensive Disorders Of Pregnancy ◽  
Endothelial Cell Function ◽  
Vascular Adaptation ◽  
Cell Dysfunction ◽  
Maternal Adaptation ◽  
Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

Shear stress regulates endothelial cell function through SRB1-eNOS signaling pathway

2016 ◽  
Vol 34 (5) ◽  
pp. 308-313 ◽  
Author(s):  
Ying Zhang ◽  
Bin Liao ◽  
Miaoling Li ◽  
Min Cheng ◽  
Yong Fu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Cell Function ◽  
Endothelial Cell Function
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