scholarly journals Characterization of Circulating Extracellular Vesicle Surface Antigens in Patients With Primary Aldosteronism

Hypertension ◽  
2021 ◽  
Author(s):  
Jacopo Burrello ◽  
Martina Tetti ◽  
Vittorio Forestiero ◽  
Vanessa Biemmi ◽  
Sara Bolis ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Primary Aldosteronism ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Surface Antigens ◽  
Bioinformatic Analysis ◽  
Extracellular Vesicle ◽  
Differentially Expressed ◽  
Unilateral Adrenalectomy

Primary aldosteronism (PA) is characterized by inappropriate aldosterone production. Chronic aldosterone excess has detrimental effects on cardiovascular system, including endothelial dysfunction and vascular inflammation. Circulating extracellular vesicles (EVs) are central players in the crosstalk between endothelium, vascular structures, and inflammatory cells. The aim of the study was to assess the potential role of EVs in aldosterone-related vascular damage by evaluating a comprehensive panel of 37 EV surface antigens. Serum EVs were isolated by immunocapture from 32 patients with PA, 29 patients with essential hypertension and from 22 normotensive controls. EVs were characterized by Western blotting, nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. Particle concentration was higher and diameter lower in patients with PA compared with controls and the number of particles decreased after unilateral adrenalectomy. Nineteen EV surface antigens were differentially expressed in patients with PA compared with patients with essential hypertension or normotensive controls, including markers of activated platelets, endothelial and immune/inflammatory cells. The specific EV surface signature discriminated patients with PA from controls, whereas after specific PA treatment the profile became similar to essential hypertension. Stimulation of human endothelial cells with PA-derived EVs resulted in the overexpression of 5 selected genes ( AKT1-CALR-CSNK2A1-FN1-PIK3R1 ), previously identified by bioinformatic analysis as targets of differentially expressed EV antigens. Overexpression of CALR and FN1 was confirmed also at protein level. Our data suggest that EVs represent biomarkers of vascular inflammation and endothelial dysfunction in patients with PA and also potential biovectors contributing to accelerated organ damage by multiple signaling processes.

scholarly journals Endothelial Dysfunction in Primary Aldosteronism

2019 ◽  
Vol 20 (20) ◽  
pp. 5214 ◽  
Author(s):  
Zheng-Wei Chen ◽  
Cheng-Hsuan Tsai ◽  
Chien-Ting Pan ◽  
Chia-Hung Chou ◽  
Che-Wei Liao ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Primary Aldosteronism ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Secondary Hypertension ◽  
Electrolyte Balance ◽  
Cerebrovascular Complications ◽  
Fundamental Cause ◽  
Artery Disease ◽  
Ischemic Attack

Primary aldosteronism (PA) is characterized by excess production of aldosterone from the adrenal glands and is the most common and treatable cause of secondary hypertension. Aldosterone is a mineralocorticoid hormone that participates in the regulation of electrolyte balance, blood pressure, and tissue remodeling. The excess of aldosterone caused by PA results in an increase in cardiovascular and cerebrovascular complications, including coronary artery disease, myocardial infarction, stroke, transient ischemic attack, and even arrhythmia and heart failure. Endothelial dysfunction is a well-established fundamental cause of cardiovascular diseases and also a predictor of worse clinical outcomes. Accumulating evidence indicates that aldosterone plays an important role in the initiation and progression of endothelial dysfunction. Several mechanisms have been shown to contribute to aldosterone-induced endothelial dysfunction, including aldosterone-mediated vascular tone dysfunction, aldosterone- and endothelium-mediated vascular inflammation, aldosterone-related atherosclerosis, and vascular remodeling. These mechanisms are activated by aldosterone through genomic and nongenomic pathways in mineralocorticoid receptor-dependent and independent manners. In addition, other cells have also been shown to participate in these mechanisms. The complex interactions among endothelium, inflammatory cells, vascular smooth muscle cells and fibroblasts are crucial for aldosterone-mediated endothelial dysregulation. In this review, we discuss the association between aldosterone and endothelial function and the complex mechanisms from a molecular aspect. Furthermore, we also review current clinical research of endothelial dysfunction in patients with PA.

scholarly journals Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension

2021 ◽  
Vol 22 (1) ◽  
pp. 147032032199949
Author(s):  
Miaomiao Sang ◽  
Yu Fu ◽  
Chenmin Wei ◽  
Jing Yang ◽  
Xueting Qiu ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Primary Aldosteronism ◽  
Cardiovascular Events ◽  
Statistical Significance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microvascular Endothelial ◽  
Pai 1 ◽  
Microvascular Endothelial Function

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.

GW24-e3740 Comparison of biomarkers of endothelial dysfunction and risk of early organ damage between primary aldosteronism and essential hypertension

Heart ◽  
2013 ◽  
Vol 99 (Suppl 3) ◽  
pp. A207.2-A207
Author(s):  
Liu Pin-Ming ◽  
Liu Gang ◽  
Zhang Shao-Ling ◽  
Yin Guo-Shu ◽  
Tang Ju-Ying ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Primary Aldosteronism ◽  
Organ Damage

Abstract 243: Roles of TNF alpha and MCP-1 in Type II Diabetes-induced Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jiyeon Yang ◽  
Abbott C Louise ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Type Ii Diabetes ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Heart Tissue ◽  
Type Ii ◽  
Necrosis Factor Alpha ◽  
Double Labeling ◽  
Monocyte Chemoattractant Protein 1

Tumor necrosis factor alpha (TNF) is reported to underlie a component of vascular inflammation and ensuing endothelial dysfunction in diabetes, but the role of inflammatory cells in these events is unknown. Because TNF reportedly induces monocyte chemoattractant protein-1 (MCP-1) expression, we hypothesized that the interaction between TNF and MCP-1 contributes to the evolution of vascular inflammation in diabetes. To test this hypothesis, expression of TNF and MCP-1, and formation of nitrotyrosine (N-Tyr, an indicator of peroxynitrite production) were determined in isolated coronary arterioles (50–100um) from genetically modified mice with Type II diabetes (Lepr db ) and the lean control heterozygotes (m Lepr db ). Protein and mRNA expression of TNF, protein expression of MCP-1, and presence of N-Tyr were significantly increased in arterioles from Lepr db mice compared to those from m Lepr db . Immunofluorescence double labeling revealed the prominent localization of MCP-1 to endothelium (Von Willebrand factor) of arterioles and venules. MCP-1 also co-localized with macrophages (CD68) in the heart tissue. To determine if MCP-1 may be key to the vascular inflammation and ensuing endothelial dysfunction, we administered anti-MCP-1 (10 μg/day, 3 days, i.p., n=4; to block MCP-1 signaling) in the mice and then determined endothelial dilation in isolated, cannulated pressurized (60 cmH2O) arterioles. Anti-MCP-1 restored dilation to acetylcholine in Lepr db mice by 35±2% (P<0.05 vs Lepr db mice without treatment, 9.8±4%) but did not affect dilation in m Lepr db mice. To establish interactions between TNF and MCP-1, we administered anti-TNF (72hr treatment; 0.625mg/kg, i.p.) to block TNF signaling and determined effects on MCP-1 and oxidative stress. After anti-TNF administration, expression of MCP-1 was decreased and numbers of MCP-1 positive cells were markedly reduced in Lepr db mice. Moreover, anti-TNF prevented the formation of N-Tyr in Lepr db mice. These findings demonstrate that the endothelial dysfunction occurring in type II diabetes is the result of the effects of the inflammatory cytokine TNF and TNF related signaling, including the expression of MCP-1, which also furthers the oxidative stress.

Essential hypertension: First reason for persistent hypertension after unilateral adrenalectomy for primary aldosteronism?

Surgery ◽  
1998 ◽  
Vol 124 (6) ◽  
pp. 1128-1133 ◽  
Author(s):  
Charles A.G. Proye ◽  
Emmanuel A.R. Mulliez ◽  
Bruno M.L. Carnaille ◽  
Martine Lecomte-Houcke ◽  
Marc Decoulx ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Primary Aldosteronism ◽  
Unilateral Adrenalectomy

P717Glucagon-like peptide 1 (GLP-1) improves endothelial dysfunction and vascular inflammation in polymicrobial sepsis induced by cecal ligation and puncture (CLP)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Steven ◽  
J Helmstaedter ◽  
F Pawelke ◽  
K Filippou ◽  
K Frenies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Endothelial Dysfunction ◽  
Knockout Mice ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Cecal Ligation And Puncture ◽  
Glucose Levels ◽  
Dpp4 Inhibitor ◽  
Cardioprotective Effects

Abstract Objective Sepsis causes severe hypotension, accompanied by high mortality in the setting of septic shock. LEADER, SUSTAIN-6 and other clinical trials revealed cardioprotective and anti-inflammatory properties of GLP-1 analogs like Liraglutide (Lira). We already demonstrated improved survival by amelioration of disseminated intravasal coagulation (DIC) in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of the GLP-1 degrading enzyme dipeptidylpeptidase-4 (DPP-4). With the present study we aim to investigate the mechanism of protective effects of the GLP-1 analog Lira and the DPP4 inhibitor Linagliptin (Lina) in the clinically relevant sepsis model cecal ligation and puncture (CLP). Methods C57/BL6j and endothelial cell-specific GLP-1 receptor knockout mice (Cdh5crexGLP-1rfl/flmice) were used and sepsis was induced by cecal ligation and puncture (CLP). DPP4 inhibitor (Lina, 5mg/kg/d; 3 days) and GLP-1 analog (Lira, 200μg/kg/d; 3 days) were applied subcutaneously. Aortic vascular function was tested by isometric tension recording. Aorta and heart tissue was used for Western blotting, dot blot and qRT-PCR. Endogenous GLP-1 (7–36 and 9–36) and insulin was determined by ELISA. Blood samples were collected for examination of cell count, oxidative stress and glucose levels. Results Body temperature was increased by CLP and normalized by Lina and Lira. Sham- and Lira- but not Lina-treated septic mice showed low blood glucose levels compared to healthy controls. Acetylcholine-induced (endothelium-dependent) vascular relaxation in aorta was impaired by CLP. This was accompanied by vascular inflammation and elevation of IL-6, iNOS, ICAM-1, and TNF-alpha mRNA levels in aortic tissue. Vascular, cardiac and whole blood oxidative stress were increased by CLP. Furthermore, we detected higher levels of IL-6, 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-NHE) in plasma of CLP animals. Lina and Lira reduced oxidative stress and vascular inflammation, which was accompanied by improved endothelial function. In addition, CLP treatment in endothelial specific knockout mice of the GLP-1r strongly induced mortality compared to WT mice, with the effect being strongest in the Lira-treated group. Conclusion The present study demonstrates that Lina (DPP4 inhibitor) and the GLP-1 analog Lira ameliorate sepsis-induced endothelial dysfunction by reduction of vascular inflammation and oxidative stress. Clinical trials like LEADER and SUSTAIN-6 proved that GLP-1 analogs like Lira have cardioprotective effects in T2DM patients. The present study, performed in a clinically relevant model of polymicrobial sepsis, reveals that the known cardioprotective effects of GLP-1 might be translated to other diseases which affect the cardiovascular system like sepsis, underlining the potent anti-inflammatory effects of GLP-1 analogs.

scholarly journals Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Active Regions ◽  
Bioinformatic Analysis ◽  
Growth Restriction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Differential Analysis ◽  
Protein Coding

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.

We-W34:4 Endothelial dysfunction predicts type 2 diabetes in essential hypertension

2006 ◽  
Vol 7 (3) ◽  
pp. 313
Author(s):  
R. Maio ◽  
M. Vatrano ◽  
G. Iemma ◽  
A. Sciacqua ◽  
F. Borrello ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Essential Hypertension ◽  
Endothelial Dysfunction
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