scholarly journals Endogenous Chemerin from PVAT Amplifies Electrical Field-Stimulated Arterial Contraction: Use of the Chemerin Knockout Rat

2020 ◽  
Vol 21 (17) ◽  
pp. 6392
Author(s):  
Emma D. Flood ◽  
Stephanie W. Watts
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Sympathetic Nerve ◽  
Mesenteric Artery ◽  
Female Rats ◽  
Electrical Field ◽  
Perivascular Adipose Tissue ◽  
Rat Mesenteric Artery ◽  
Arterial Contraction ◽  
Isolated Rat

Background: We previously reported that the adipokine chemerin, when added exogenously to the isolated rat mesenteric artery, amplified electrical field-stimulated (EFS) contraction. The Chemerin1 antagonist CCX832 alone inhibited EFS-induced contraction in tissues with but not without perivascular adipose tissue (PVAT). These data suggested indirectly that chemerin itself, presumably from the PVAT, facilitated EFS-induced contraction. We created the chemerin KO rat and now test the focused hypothesis that endogenous chemerin amplifies EFS-induced arterial contraction. Methods: The superior mesenteric artery +PVAT from global chemerin WT and KO female rats, with endothelium and sympathetic nerve intact, were mounted into isolated tissue baths for isometric and EFS-induced contraction. Results: CCX832 reduced EFS (2–20 Hz)-induced contraction in tissues from the WT but not KO rats. Consistent with this finding, the magnitude of EFS-induced contraction was lower in the tissues from the KO vs. WT rats, yet the maximum response to the adrenergic stimulus PE was not different among all tissues. Conclusion: These studies support that endogenous chemerin modifies sympathetic nerve-mediated contraction through Chemerin1, an important finding relative in understanding chemerin’s role in control of blood pressure.

scholarly journals The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery

2016 ◽  
Vol 311 (2) ◽  
pp. H498-H507 ◽  
Author(s):  
Emma S. Darios ◽  
Brittany M. Winner ◽  
Trevor Charvat ◽  
Antoni Krasinksi ◽  
Sreenivas Punna ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Superior Mesenteric Artery ◽  
Sympathetic Nerve ◽  
Mesenteric Artery ◽  
Sympathetic Innervation ◽  
Electrical Field ◽  
Perivascular Adipose Tissue ◽  
Sympathetic Nervous

The adipokine chemerin causes arterial contraction and is implicated in blood pressure regulation, especially in obese subjects with elevated levels of circulating chemerin. Because chemerin is expressed in the perivascular adipose tissue (PVAT) that surrounds the sympathetic innervation of the blood vessel, we tested the hypothesis that chemerin (endogenous and exogenous) amplifies the sympathetic nervous system in mediating electrical field-stimulated (EFS) contraction. The superior mesenteric artery, with or without PVAT and with endothelium and sympathetic nerve intact, was mounted into isolated tissue baths and used for isometric contraction and stimulation. Immunohistochemistry validated a robust expression of chemerin in the PVAT surrounding the superior mesenteric artery. EFS (0.3–20 Hz) caused a frequency-dependent contraction in isolated arteries that was reduced by the chemerin receptor ChemR23 antagonist CCX832 alone (100 nM; with, but not without, PVAT), but not by the inactive congener CCX826 (100 nM). Exogenous chemerin-9 (1 μM)-amplified EFS-induced contraction in arteries (with and without PVAT) was blocked by CCX832 and the α-adrenergic receptor antagonist prazosin. CCX832 did not directly inhibit, nor did chemerin directly amplify, norepinephrine-induced contraction. Whole mount immunohistochemical experiments support colocalization of ChemR23 with the sympathetic nerve marker tyrosine hydroxylase in superior mesenteric PVAT and, to a lesser extent, in arteries and veins. These studies support the idea that exogenous chemerin modifies sympathetic nerve-mediated contraction through ChemR23 and that ChemR23 may be endogenously activated. This is significant because of the well-appreciated role of the sympathetic nervous system in blood pressure control.

scholarly journals Long-term cardiac risk in individuals with low calcium score on coronary computed tomography angiography can be stratified by the pericoronary fat radiomic profile (FRP)

2021 ◽  
Vol 22 (Supplement_3) ◽  
Author(s):  
CP Kotanidis ◽  
EK Oikonomou ◽  
MC Williams ◽  
S Thomas ◽  
KE Thomas ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Computed Tomography ◽  
Blood Pressure ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Coronary Computed Tomography Angiography ◽  
Cardiac Risk ◽  
Tissue Composition ◽  
Perivascular Adipose Tissue ◽  
Adjusted Risk

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): UKRI, British Heart Foundation Background Inflammation in the coronaries induces macroscopic changes in perivascular adipose tissue composition, detectable by the pericoronary Fat Radiomic Profile (FRP) on coronary computed tomography angiography (CCTA). Purpose To assess the ability of FRP to stratify cardiac risk in patients with Coronary Artery Calcium (CAC) score below 100 following routine CCTA. Methods 1,575 participants from the CCTA arm of the SCOT-HEART trial (NCT01149590) eligible for image analysis were included. Pericoronary FRP mapping was performed in perivascular adipose tissue segmentations around the proximal sites of the right and left coronary arteries, as previously validated. We first tested the prognostic value of FRP in the sub-cohort of patients with CAC < 100. We further analysed a sub-group based on the absence of high risk plaque (HRP) features and obstructive coronary artery disease (CAD). The association with future incidence of major adverse cardiac events (MACE: cardiac mortality or non-fatal myocardial infarction) or a composite endpoint of MACE ± late revascularization (MACE-ReVasc) was assessed using adjusted Cox regression models [adjusted for age, sex, systolic blood pressure (SBP), diabetes mellitus (DM), body mass index (BMI), smoking, CAD (≥50% stenosis), total cholesterol, high-density lipoprotein (HDL), and HRP features]. Results In total, 1,032 patients (53.9% female sex) were found with low CAC score (CAC < 100), with a median age of 55 years. Over a mean follow-up of 4.87 ± 1.06 years, 12 MACE and 47 MACE-ReVasc were recorded. High FRP was associated with a 14.4-fold (95% CI: 3.80-54.78, p < 0.001) higher adjusted risk of MACE and a 2.8-fold (95% CI: 1.49-5.36, p = 0.001) higher adjusted risk of MACE-ReVasc (A). Addition of high FRP to a baseline model consisting of traditional risk factors (age, sex, systolic blood pressure, diabetes mellitus, BMI, smoking, CAD (≥50% stenosis), total cholesterol, HDL, HRP) significantly enhanced (deltaAUC at 5 years:0.15, p = 0.03) the model’s performance and reclassified individuals (NRI = 0.59, p = 0.02, B). Interestingly, after more rigorous filtering of the population by absence of HRP features and obstructive CAD, high FRP remained an independent predictor of MACE (n = 756, Adj.HR = 28.1, p = 0.003). Conclusion In individuals with low CAC scores the Fat Radiomic Profile biormarker significantly improves risk prediction for adverse clinical events beyond the current state-of-the-art. Non-invasive profiling of pericoronary adipose tissue using CCTA-derived FRP captures irreversible changes in perivascular adipose tissue composition associated with chronic vascular inflammation and atherosclerotic disease, and can supplement the traditional anatomical assessment of the coronary vasculature with a functional marker of disease activity.

Abstract P102: Liver Acquitted, Fat Indicted: Hepatic Chemerin Knockdown Does Not Reduce Blood Pressure While Whole-body Knockdown Does

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
David J Ferland ◽  
Bridget Seitz ◽  
Emma S Darios ◽  
Janice M Thompson ◽  
Steve T Yeh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Reduce Blood Pressure ◽  
Blood Pressure Regulation ◽  
Whole Body ◽  
Pressure Regulation ◽  
Perivascular Adipose Tissue ◽  
Subcutaneous Injections ◽  
Arterial Blood ◽  
Phosphate Buffered Saline

Chemerin is an inflammatory adipokine positively associated with hypertension and obesity with the majority of chemerin thought to derive from the liver and adipose tissue. The contributions of liver-derived chemerin to plasma chemerin levels and blood pressure regulation are unknown. We compared whole-body vs liver chemerin inhibition using antisense oligonucleotides (ASO) with liver-restricted activity (GalNAc) or liver and fat activity (Gen 2.5). We hypothesized that in normotensive male SD rats, circulating chemerin is predominately liver-derived and regulates blood pressure. A scrambled ASO control and phosphate-buffered saline (PBS) were used as controls and radiotelemetry was used to monitor blood pressure. Baseline mean arterial blood pressure (MAP) was recorded for one week, beginning 5 days after surgery to establish a baseline. ASOs were given weekly by subcutaneous injections for four weeks. Two days after the final injection, animals were sacrificed for tissue RT-PCR and plasma chemerin measurements using Western analysis. Gen 2.5 chemerin ASO treatments (compared to PBS control) reduced chemerin mRNA in liver, retroperitoneal fat, and mesenteric perivascular adipose tissue (mPVAT) by 99.5% ± 0.1%, 95.2% ± 0.3%, and 69% ± 2%, respectively, and plasma chemerin was reduced to undetectable levels. GalNAc chemerin ASO treatments (compared to PBS control) reduced chemerin mRNA in liver by 97.9% but had no effect on chemerin expression in retroperitoneal fat and mPVAT; plasma chemerin was reduced by 90% ± 5%. Gen 2.5 chemerin ASO treatment reduced MAP, which reached a nadir of 7 ± 2.1 mmHg 48 – 72 hours after each dose compared to the scrambled ASO controls. By contrast, MAP was unchanged in animals receiving the GalNAc chemerin ASO. Thus, although most circulating chemerin is liver-derived, plasma chemerin does not play a role in blood pressure regulation. This study suggests that while chemerin is still generally associated with increased blood pressure, circulating chemerin levels cannot directly predict this effect. In addition, local effects of chemerin from fat may explain this discrepancy and support chemerin’s association with both hypertension and obesity.

Abstract P099: Loss Of The Brown-Like Phenotype Of Aortic PVAT Is Associated With Mitochondrial Dysfunction In Obesity-Induced Endothelial Dysfunction In Female Rats

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Nicole Maddie ◽  
Maria Alicia A Carrillo-sepulveda
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Mitochondrial Dysfunction ◽  
Uncoupling Protein ◽  
Obese Group ◽  
Female Rats ◽  
Chow Diet ◽  
Anatomical Location ◽  
Perivascular Adipose Tissue

Endothelial dysfunction is a major complication of obesity and is an early contributor to hypertension. Perivascular adipose tissue (PVAT) surrounds most blood vessels and has different phenotypic properties based on its anatomical location. Thoracic aortic PVAT from humans and rodents is a brown-like adipose tissue and plays a vasculo-protective role under physiological conditions. In obesity, aortic PVAT expands, switches from a brown-like to a white-like phenotype and contributes to endothelial dysfunction. We hypothesized that loss of the brown-like phenotype of aortic PVAT in obesity is associated with mitochondrial dysfunction, resulting in PVAT and endothelial dysfunction. Eight-week-old female Wistar rats were randomized into two experimental groups: the Lean group (n=8) received a chow diet (5% fat, 48.7% carbohydrate [3.2% sucrose], 24.1% protein) and the Obese group (n=8) received a western diet (21% fat, 50% carbohydrate [34% sucrose], 20% protein), for 20 weeks. Increased body weight (340.57 vs. 265.37g leans, p<0.05) was confirmed in the obese group. At the experimental endpoint, thoracic aortas with intact (+PVAT) or removed PVAT (-PVAT) were obtained for analysis. Endothelial function was assessed in aortic rings +PVAT or -PVAT by performing concentration-response to acetylcholine using wire myography. The aortic ring (-PVAT) from the obese group exhibited impaired endothelium-dependent vasodilation (p<0.01). This effect was heightened in aortic rings (+PVAT) (p<0.05), showing a negative effect of PVAT on endothelial function during obesity. Mitochondrial dysfunction in PVAT from the obese group was characterized by decreased mitochondrial density (30% reduction, p<0.05), detected by quantification of Mitotracker fluorescence, and increased reactive oxygen species levels (4.34-fold increase, p<0.01), as evidenced by DHE staining. These effects were accompanied by decreased uncoupling protein-1 expression in the obese group (55% reduction, p<0.01). Moreover, Oil Red O staining showed larger lipid droplets in aortic PVAT from the obese group. Our results support that obesity-induced endothelial dysfunction is associated with a loss of the brown-like phenotype and mitochondrial dysfunction in PVAT.

P735Interleukin-33 induced eosinophilia restores perivascular adipose tissue function in obesity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Saxton ◽  
R J Potter ◽  
S B Withers ◽  
R Grencis ◽  
A M Heagerty
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Plasma Insulin ◽  
Vascular Tone ◽  
Mesenteric Arteries ◽  
Obese Mice ◽  
High Fat ◽  
Perivascular Adipose Tissue

Abstract Background/Purpose Perivascular adipose tissue (PVAT) is essential in the modulation of vascular tone. Recently we have shown that resident eosinophils play a vital role in regulating PVAT function. In obesity, eosinophil numbers are reduced and PVAT anticontractile function is lost, resulting in increased vascular tone, which will contribute to development of hypertension and type-2 diabetes. Evidence suggests that eosinophilia resulting from parasitic infection may be useful in improving glucose tolerance; therefore, we investigated the effects of eosinophilia on PVAT function in health and obesity. Methods Control mice and a high fat fed mouse model of obesity were administered intraperitoneal injections of interleukin-33 (IL-33, 0.1μg) over a five day period. Blood pressure, blood glucose and plasma insulin were measured and compared with un-injected control and obese mice. Wire myography was used to assess the vascular contractility of mesenteric arteries (<250μm, +/− PVAT) from both injected and un-injected control and obese mice in response to noradrenaline. ELISAs and immunohistochemistry were used to examine eosinophil numbers. Results High fat feeding induced significant elevations in blood pressure, blood glucose and plasma insulin, which were reduced using IL-33 injections. Eosinophilia was confirmed in blood plasma using an eosinophil cationic protein ELISA. Using wire myography, mesenteric arteries from control mice PVAT exerted an anticontractile effect on the vessels, which was enhanced in control mice injected with IL-33. In obese mice, the PVAT anticontractile effect was lost, but was restored in IL-33 injected obese mice. Using immunohistochemistry, we confirm that eosinophils numbers in PVAT were reduced in obesity and increased in IL-33 treated PVAT. Conclusions IL-33 injections induced eosinophilia in both control and obese mice. IL-33 treatment restored PVAT function in obesity, and enhanced the anticontractile function of PVAT in healthy animals. In addition, only five consecutive injections of IL-33 reversed development of hypertension and type-2 diabetes in obese mice. These data suggest that IL-33 induced eosinophilia presents a novel approach to treatment of hypertension and type-2 diabetes in obesity. Acknowledgement/Funding British Heart Foundation

scholarly journals Vasorelaxant Effect Induced by the Essential Oil of Ocotea duckei Vattimo Leaves and Its Main Constituent, Trans-caryophyllene, in Rat Mesenteric Artery

2020 ◽  
pp. 31-39
Author(s):  
Tays Amanda Felisberto Gonçalves ◽  
Renildo Moura da Cunha ◽  
Dionatas Ulises de Oliveira Meneguetti ◽  
Marcio Roberto Viana Santos ◽  
José Maria Barbosa- Filho ◽  
...  
Keyword(s):  
Essential Oil ◽  
Mesenteric Artery ◽  
Calcium Release ◽  
Mesenteric Arteries ◽  
Dependent Manner ◽  
Main Constituent ◽  
Response Curves ◽  
Vasorelaxant Effect ◽  
Rat Mesenteric Artery ◽  
Isolated Rat

Aims: To evaluate the vasorelaxant effect induced by the essential oil of the leaves of O. duckei Vattimo (ODEO) and its main constituent, trans-caryophyllene, in rat superior mesenteric arteries. Methodology: Isolated rat superior mesenteric rings were suspended by cotton threads for isometric tension recordings in Tyrode’s solution at 37ºC, gassed with 95% O2 and 5% CO2 and different ODEO concentrations (0.1-300 μg/mL) or trans-caryophyllene (1-1000 μg/mL) were added cumulatively to the organ baths. Results: Vasorelaxant effect induced by the essential oil of Ocotea duckei leaves (ODEO) and its main constituent, trans-caryophyllene (60.54 %), was evaluated in this work. In intact isolated rat superior mesenteric rings ODEO (0.1-300 μg/mL, n=6) induced concentration-dependent relaxation of tonus induced by phenylephrine (10 µM) or K+-depolarizing solution (KCl 80 mM) (IC50=31±5, 5±0.4 µg/mL, respectively, n=6). The relaxations of phenylephrine-induced contractions were not significantly attenuated after removal of the vascular endothelium (IC50=25±5 µg/mL). ODEO antagonized the concentration-response curves to CaCl2 (10-6-3x10-2 M) and Bay K 8644 (10-10-3x10-6 M). Furthermore, in nominally without calcium solution, ODEO significantly inhibited, in a concentration-dependent manner, transient contractions induced by 10 µM phenylephrine or 20 µM caffeine. Trans-caryophyllene induced vasorelaxations, however, this effect was 18.6 times less potent when compared to ODEO-induced vasorelaxations. Conclusion: The relaxant effect induced by ODEO in rat superior mesenteric artery rings is endothelium-independent and seems to be related to both, inhibition of Ca2+ influx through L-type voltage-gated Ca2+-channels sensitive to dihydropyridines and inhibition of the calcium release from intracellular IP3-and caffeine-sensitive stores.

scholarly journals Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure Through Transcriptional Regulation of Angiotensinogen

Circulation ◽  
2018 ◽  
Vol 138 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Lin Chang ◽  
Wenhao Xiong ◽  
Xiangjie Zhao ◽  
Yanbo Fan ◽  
Yanhong Guo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Transcriptional Regulation ◽  
Perivascular Adipose Tissue
Sign in / Sign up

Export Citation Format

Share Document