Abstract 46: Vascular Endothelium-derived Endothelin 1 Promotes Salt-induced Kidney Inflammation In Male But Not Female Mice

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Patrick Molina ◽  
Sara Biswal ◽  
Jennifer S Pollock ◽  
Carmen De Miguel ◽  
Claudia Edell
Keyword(s):  
Inflammatory Responses ◽  
Vascular Endothelial Cell ◽  
Organ Damage ◽  
High Salt ◽  
Vascular Endothelial ◽  
Absolute Count ◽  
Male And Female ◽  
Cell Numbers ◽  
Endothelin 1 ◽  
And Control

Endothelin 1 (ET-1), potent vasoactive and pro-inflammatory peptide, plays a criticalrole in hypertension and end-organ damage. The inflammatory response to high saltintake displays sex differences; however, if a sex difference exists in vascular ET-1inducing salt-induced kidney inflammation is unknown. We aimed to assess the role ofendothelium-derived ET-1 in promoting kidney inflammation in male and female micefed high salt. Aged-matched male and female vascular endothelial cell ET-1 knockout(VEET KO) and control floxed ET-1 (VEET fl/fl ) mice were fed 4.0% NaCl chow (HSD).After 3 weeks of HSD, kidney myeloid and lymphoid cell populations and their functionalstatus were examined by flow cytometry. In response to HSD, male VEET fl/fl mice hadsignificantly higher kidney TH17 cell numbers than female VEET fl/fl mice (IL-17A + CD4 + cell absolute count, male vs. female: 229.6±27.7 vs. 84.9±17.2, p=0.0003, n=6-10/group), indicating a substantial sex-dependent difference in kidney TH17 cellabundance. Lack of endothelium-derived ET-1 resulted in 72% reduction in renal TH17cell number in males (VEET fl/fl vs. VEET KO: 229.6±27.7 vs 64.0±64, p=0.0002), but notin females (p>0.05). Frequency of kidney IL-17A + CD4 + cells was not different betweengenotypes in females or between male and female VEET fl/fl mice. However, male VEETKO mice displayed 57% less renal IL-17A + CD4 + cells than male VEET fl/fl (respectively,0.6±0.071 vs. 1.4±0.2, p=0.0055), and 59% reduction compared to female VEET KOmice (1.4±0.2, p=0.0052). Assessment of the effects of vascular ET-1 on the innateimmune response showed that activated kidney resident macrophages(F4/80 hi CD11b + CD64 + ) were increased in male vs. female VEET fl/fl (MFI, respectively,2080±105 vs. 1672±25, p=0.0002). Lack of endothelium-derived ET-1 significantlyreduced CD64 abundance in males (p=0.012), but not females (p>0.05), whencompared to VEET fl/fl . In conclusion, endothelium-derived ET-1 is critical in promotingrenal innate and adaptive inflammatory responses in males in response to high salt, andimportant male-female differences exist in the manner by which vascular ET-1 regulateskidney inflammation in this setting. Funded by NIH F31 HL151264-0 to PAM,P01HL136267 to JSP, and K01HL145324 to CDM.

scholarly journals Progesterone blunts vascular endothelial cell secretion of endothelin-1 in response to placental ischemia

2013 ◽  
Vol 209 (1) ◽  
pp. 44.e1-44.e6 ◽  
Author(s):  
Luissa V. Kiprono ◽  
Kedra Wallace ◽  
Janae Moseley ◽  
James Martin ◽  
Babbette LaMarca
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Cell Secretion ◽  
Endothelin 1 ◽  
Placental Ischemia

scholarly journals Inhibitory Effect of Chinese Propolis on Phosphatidylcholine-Specific Phospholipase C Activity in Vascular Endothelial Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Hongzhuan Xuan ◽  
Ruiliang Zhu ◽  
Yajing Li ◽  
Fuliang Hu
Keyword(s):  
Phospholipase C ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Oxygen Species ◽  
High Concentration ◽  
Inflammatory Action ◽  
Chinese Propolis

To understand the mechanisms underlying the anti-inflammatory action of Chinese propolis, we investigated its effect on the activity of phosphatidylcholine-specific phospholipase C (PC-PLC) that plays critical roles in control of vascular endothelial cell (VEC) function and inflammatory responses. Furthermore, p53 and reactive oxygen species (ROS) levels and mitochondrial membrane potential (Δψm) were investigated. Our data indicated that treatment of Chinese propolis 6.25 and 12.5 μg/ml for 12 hours increased VEC viability obviously. Exposure to Chinese propolis 6.25, 12.5, and 25 μg/ml for 6 and 12 hours significantly decreased PC-PLC activity and p53 level, and ROS levels were depressed by Chinese propolis 12.5 μg/ml and 25 μg/ml dramatically. TheΔψm of VECs was not affected by Chinese propolis at low concentration but disrupted by the propolis at 25 μg/ml significantly, which indicated that Chinese propolis depressed PC-PLC activity and the levels of p53 and ROS in VECs but disruptedΔψm at a high concentration.

Abstract 3556: Diabetic Cardiac and Renal Complications are attenuated in Mice with Conditional Knockout of Endothelin-1 in Vascular Endothelial Cell

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Bambang Widyantoro ◽  
Suko Adiarto ◽  
Naoko Iwasa ◽  
Kazuhiko Nakayama ◽  
Dyah W Anggrahini ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Interstitial Fibrosis ◽  
Vascular Endothelial Cell ◽  
Conditional Knockout ◽  
Vascular Endothelial ◽  
Endothelin 1 ◽  
Renal Complications ◽  
Renal Complication ◽  
Lower Expression

High plasma endothelin-1 (ET-1) level has been associated with diabetic cardiovascular and renal complications, which remained prevalent despite good glycemic control. Since endothelial dysfunction, which is characterized by enhanced ET-1 secretion, plays an important role in mediating diabetic complication, we hypothesized that disruption of ET-1 in endothelial cell will be protective against cardiac and renal complication of diabetes. To test this hypothesis, we injected streptozotocin to Vascular Endothelial cell Specific Endothelin-1 Knockout (VEETKO) mice, of which ET-1 expression in major organs including heart and kidney were reduced by 60%, and to their wild type (WT) littermates. Six months of diabetes increased systolic blood pressure (SBP) similarly in both genotypes, with DM-VEETKO mice have remained lower SBP than DM-WT mice (124±1.08 vs. 131.33±1.33 mmHg, p<0.01, n=8 each). Diabetes also exaggerated the difference in cardiac ET-1 mRNA expression between both groups. The heart of DM-VEETKO mice showed lower area of interstitial fibrosis as compared to DM-WT mice, and this is associated with lower expression of fibrotic genes (TGF-β, CTGF and Collagen-1), higher capillary density (as measured by CD-31 staining) and higher VEGF mRNA expression. Furthermore, eight months of diabetes decreased cardiac systolic function of all mice, however, the decrease is significantly attenuated in DM-VEETKO mice (fractional shortening 45.67±0.61 vs. 38.27±2.2%, p<0.01, n=4 each). Similarly, DM-VEETKO mice also preserved renal function. Diabetes caused an increase in urinary protein excretion with the values in DM-VEETKO mice being approximately one fifth of DM-WT mice (30.12±10.09 vs. 170±23.19 mg/dl, p<0.01, n=6 each) Morphologically, DM-VEETKO mice have less glomerular fibrosis which is associated with lower expression of ICAM-1, and further leads to lower glomerular macrophage recruitment. In conclusion, these findings indicate that disruption of ET-1 in endothelial cell is significantly attenuated diabetic cardiovascular and renal complication in streptozotocin-induced diabetic mice model, and may provide additional basic rationales for the use of ET-1 blockade for the prevention of cardiac and renal complication of diabetes.

scholarly journals Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation

2009 ◽  
Vol 82 (1) ◽  
pp. 143-151 ◽  
Author(s):  
Dyah W. Anggrahini ◽  
Noriaki Emoto ◽  
Kazuhiko Nakayama ◽  
Bambang Widyantoro ◽  
Suko Adiarto ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Cell ◽  
Vascular Inflammation ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Neointima Formation ◽  
Endothelin 1

Effect of angiotensin(1-7) on the expression of E-selectin induced by angiotensinII and its mechanism in vascular endothelial cell

2010 ◽  
Vol 34 (8) ◽  
pp. S71-S71
Author(s):  
Xiaohui Shen ◽  
Zhi‑Bin Wen ◽  
Na Li ◽  
Qingmei Cheng ◽  
Xiaofan He ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

Early predictors of placental dysfunction

2016 ◽  
pp. 25-28
Author(s):  
J.M. Melnik ◽  
◽  
A.A. Shlyahtina ◽  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Pregnant Women ◽  
Umbilical Artery ◽  
Placental Growth Factor ◽  
Vascular Endothelial ◽  
Endothelin 1 ◽  
Placental Dysfunction ◽  
Early Predictors ◽  
Endothelial Growth Factor

The article presents the predictors of placental dysfunction on the early stage of pregnancy. The objective: the search for prognostic markers and criteria for the occurrence of placental insufficiency in the early stages of the gestational process to optimize the pregnancy and labor with improved perinatal outcomes. Patients and methods. To solve this goal in the period from 2013 to 2015 were conducted a comprehensive survey of 334 pregnant women, which depending on the peculiarities of pregnancy and childbirth were divided into groups. The control group consisted of 236 pregnant women with uncomplicated gestational period, no morphological signs of placental dysfunction. The study group included 98 patients with a complicated pregnancy who had revealed violations of the fetal-placental relations, which was confirmed by morphological examination of the placenta in the postpartum period. Results. It was found that pregnant women with placental insufficiency in the first trimester of pregnancy have higher levels of interleukin-1B (IL-1v) and interleukin-3 (IL-3) in comparison with physiological pregnancy, as well as there is a direct significant correlation between IL-1v and pulsative index (PI) in the spiral (r=0.84) and uterine artery (r=0.77), and the inverse correlation between the level of IL-3 and PI in the terminal branches of the umbilical artery (r=-0.69). Verified an inverse relationship between the concentration of endothelin-1, the level of vascular endothelial growth factor (r=-0.87) and placental growth factor (r=-0.73), and also a direct link between the content of endothelin-1 and PI in spiral arteries (r=0.89), uterine artery (r=0.83) and the terminal branches of the umbilical artery (r=0.79). Conclusion. Thus, it is proven that early predictors of placental dysfunction can be considered the concentration of endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin-1, interleukin-3, and the indices of pulsative index. Key words: placental dysfunction, predictors, endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin, pulsative index.

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