bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial ACKR3 drives atherosclerosis by promoting immune cell adhesion to vascular endothelium
Authors: Van Der Vorst E , Gencer S , Jansen Y , Bayasgalan S , Yan Y , Bianchini M , Cimen I , Mueller M , Peters L , Megens R , Duchene J , Lemnitzer P , Soehnlein O , Weber C , Doering Y 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft SFB1123
European Research Council AdG_692511

Background
Genome wide association studies revealed a strong association between the CXCL12 gene locus and cardiovascular diseases, highlighting its receptors CXCR4 and atypical chemokine receptor-3 (ACKR3) as targets for CVD research. Although vascular CXCR4 is well studied in atherosclerosis, the exact role of ACKR3 remains elusive. Therefore, the aim of this project is to decipher the role of vascular ACKR3 in atherosclerosis.

Methods
Vascular endothelium (Bmx-cre) specific Ackr3 deficient mice on Apoe-/- background were fed with a cholesterol-rich diet. Lesions in the aortic roots and arches were analyzed via H&E staining. The phenotype was further characterized employing ex-vivo perfusion and intravital microscopy for cell adhesion and Evans-blue injection for endothelial permeability. Signaling studies are performed in human coronary artery endothelial cells (HCAECs).

Results
Endothelial Ackr3 deficiency resulted in significantly smaller atherosclerotic lesions, accompanied by a more stable plaque phenotypes (more lesional collagen and smooth muscle cell content, smaller necrotic cores). Endothelial-Ackr3-/- mice revealed a reduction in plaque macrophage content and ICAM positive endothelial cells in atherosclerotic lesions. Moreover, immune cell adhesion on carotid arteries lacking endothelial ACKR3 was decreased whilst endothelial permeability was not affected. ACKR3 silencing in TNF-stimulated HCAECs decreased adhesion molecule expression and downregulated MAPK signaling and NF-kB p65 phosphorylation. Endothelial cells in atherosclerotic lesions also revealed decreased phospho-NF-kB p65 expression in Ackr3 deficient mice.

Conclusion
Collectively, our findings indicate that arterial endothelial ACKR3 fuels atherosclerosis by mediating endothelium-immune cell adhesion, most likely through inflammatory MAPK and NF-kB pathways resulting in increased adhesion molecule expression.
Smooth muscle cell-specific deletion of S100A4 reroutes smooth muscle cell fate and modifies the inflammatory status of murine atherosclerotic lesions
Authors: Cardoso Dos Santos LM , Azar P , Lemeille S , Bochaton-Piallat ML 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): Swiss National Science Foundation
Foundation Centre de Recherches Médicales Carlos and Elsie de Reuter
Background aims: S100A4, a small calcium binding protein, plays an important role in vascular smooth muscle cell (SMC) phenotypic switch but its implication in atherosclerotic plaque development and particularly in SMC phenotypic plasticity is not clear yet. By neutralizing S100A4 using a monoclonal antibody, we have previously shown a reduction in overall atherosclerotic burden. However, this strategy did not distinguish the different contribution between SMCs or other S100A4-expressing cells (e.g. macrophages).

Methods
Herein, we used a lineage tracing mouse model in which we induced a SMC specific deletion of S100A4 (SMC-S100A4Δ/Δ) in an ApoE-/- background. High cholesterol diet was maintained for 12 weeks, after which, SMC-S100A4Δ/Δ and control mice (SMC-S100A4wt/wt) were sacrificed and aortas processed for staining and single cell RNA sequencing (scRNA-seq).

Results
We showed that S100A4 deletion modulated plaque composition rather than plaque size. ScRNA-seq analysis from SMC-S100A4Δ/Δ and SMC-S100A4wt/wt showed a reduction in macrophages and dendritic cells and an increase in total SMCs, likely participating in fibrous cap stabilization. SMC populations showed a decrease in macrophage-like inflammatory phenotype and an increase in fibroblast-like repair phenotype, as well as retention of specific SMC markers, namely Acta2 and Myh11. Gene expression analysis revealed a reduction in the expression of inflammation markers, fatty acid metabolism, and extracellular matrix-related genes, and an increase in classical SMC markers and maintenance of the contractile phenotype.

Conclusion
We report an intrinsic function of S100A4 in the establishment of SMC fate within the plaque and, surprisingly, a global impact on the atherosclerotic plaque microenvironnement and inflammation status.
SVEP1 is a new regulator of arterial tone
Authors: Morris GE , Denniff MJ , Kostogrys RB , Bountziouka V , Rainbow RD , Samani NJ , Webb TR 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Introduction
Vascular tone is regulated by the relative contractile state of vascular smooth muscle cells (VSMCs). Several integrins can directly modulate VSMC contraction by regulating calcium influx through L-type voltage-gated Ca2+ channels (VGCCs). Integrin α9β1 has been identified as preventing exaggerated airway bronchiole contraction. Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin α9β1, are associated with elevated blood pressure, however, neither SVEP1 nor integrin α9β1 have a reported role in vasoregulation.

Purpose
To determine whether SVEP1 and integrin α9β1 regulate blood vessel contraction.

Methods & Results
Animal experimentation was performed according to ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines and "the Principles of laboratory animal care". Immunocytochemical staining showed both ligand and receptor co-localised within the medial layer of the aorta, and in smooth muscle cells in the mesenteric artery. siRNA inhibition of SVEP1 or integrin α9β1 significantly enhanced real-time [Ca2+]i release in isolated human VSMCs to several Gαq/11-vasoconstrictors and to UTP in VSMCs isolated from Svep1+/- mice (Fig. 1A, n=5, P&lt;0.0001). This enhanced cellular contraction was confirmed in blood vessels by wire myography where aortic rings and mesenteric arteries (Fig. 1B, n=10 P&lt;0.0001) from Svep1+/- mice contracted at significantly higher levels than littermate controls. Similar responses were seen in aortic rings when integrin α9β1 was inhibited using the small molecule inhibitor BOP (n=10 P&lt;0.001). Inhibition of VGCCs using nifidepine, or PKC using bisindolylmaleimide (I) prevented this enhanced contraction, suggesting this effect is mediated via VGCCs in a PKC dependent mechanism.

Conclusions
Our studies reveal a novel role for SVEP1 and integrin α9β1 in reducing vascular hyper-contractility in response to a range of vasoconstrictor agonists through an L-type voltage gated Ca2+ channel-mediated effect. This regulatory mechanism could suggest a possible explanation for the genetic associations with blood pressure, and provide a new treatment strategy for hypertension.
Characterization of the source(s) of lipocalin-2 mediating dietary obesity-induced hypertension
Authors: Konja D , Li H , Fu B , Singh S , Wang Y 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): This work was supported by the grants from the General Research Funds (17117017 and 17121714) and Collaborative Research Funds (C7037-17W) of Research Grant Council, the Areas of Excellence Scheme (AoE/M-707/18) of University Grants Committee
Title: Characterization of the source(s) of lipocalin-2 mediating dietary obesity-induced hypertension.

Introduction
Obesity upregulates lipocalin-2 (Lcn2), a pro-inflammatory adipokine, which in turn induces vascular and metabolic abnormalities. In mice, deletion of the Lcn2 alleles has protective effects against obesity-induced vascular and metabolic dysfunctions.

Purpose
The present study investigated the sources of lipocalin-2 production as a mediator of dietary obesity-associated perivascular adipose tissue dysfunction and hypertension.

Methods
The wild type (WT) littermates or mice with whole body knockout (LKO), adipose tissue (Adn-Cre)-, kidney (Wt1-Cre)-, liver (Alb-Cre)-, and granuloid cells (Lys-Cre)-selective deletion of the Lcn2 alleles were implanted with radio-telemetry transmitters at eight-weeks of age. Blood pressure was recorded at least four 12/12 light-dark cycles every four weeks for mice fed either standard chow (STC) or high fat diet (HFD). Wire myography was performed to evaluate the functional properties of mesenteric arteries, in the presence or absence of surrounding perivascular adipose tissues. Quantitative PCR, Western blotting as well as enzyme-linked immunosorbent assay (ELISA) were also performed to measure Lcn2 expression in tissues and blood respectively.

Results
Compared to STC, HFD feeding increased systolic, diastolic, mean arterial and pulse pressure in WT mice. The amount of Lcn2 expressed in perivascular adipose tissues and present in blood were also higher in HFD-fed WT mice when compared to those fed with STC. Whole body deletion of Lcn2 alleles attenuated HFD- induced increase in blood pressure. Liver-selective deletion of Lcn2 alleles abolished the effect of HFD feeding on blood pressure, decreased Lcn2 expression in perivascular adipose tissues, and the concentration of Lcn2 in blood. Both whole body- and liver-specific deletion of Lcn2 alleles enhanced the anti-contractile activity of perivascular adipose tissues and abolished HFD-induced adipose tissue dysfunction. However, deletion of Lcn2 alleles selectively in adipose tissues, but not Wt1-Cre and Lys-Cre, partially mitigated the effects of HFD on perivascular adipose tissue function and blood pressure regulation.

Conclusion
Lcn2 derived from different tissues are distinctively implicated in dietary obesity-induced perivascular adipose tissue dysfunction and hypertension.
Adipose mesenchymal stem cells from different fat depots in obese and lean subjects have different microRNA signatures involved in their differentiation into endothelial cells
Authors: Civit-Urgell A , Badimon L , Arderiu G 
Published: June 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III - Fondo de Investigaciones Sanitarias (FIS) P20/01517 to GA and Spanish Ministry of Science and Innovation PID 2019-107160RB-I00 to LB. All grants were co-financed by European Union Funds, Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa".
Background/Introduction: Cell-based regenerative medicine has emerged as the forefront therapeutic procedure to improve ischemic tissue recovery. This approach is based on the usage of multilineage stem cells that can contribute to tissue regeneration. Revascularization of ischemic tissues is one of the objectives of cell therapy1,2. In this regard, we have investigated adipose-derived stem cells (ASCs), multipotent adult mesenchymal stems cells, as a cell source for therapy because of their capability to differentiate into endothelial cells (ECs)3–5. The regulatory mechanisms that drive the differentiation to EC are under investigation.

Purpose
Our hypothesis is that microRNAs (miRNAs) are involved in ASC to EC differentiation by a defined genetic signature in each fat tissue depot. The understanding of these mechanisms may be used to promote neovascularization in ischemic tissue.

Methods
Human ASCs from white adipose tissue (WAT) were obtained by surgical procedures from lean and obese patients. Importantly, subcutaneous-WAT and visceral-WAT were obtained from the same obese patient. ASCs from fat depots of lean and obese subjects where induced to differentiate into endothelial cells. The expression of 2025 pre-miRNAs and 2578 mature miRNAs was assessed using miRNA arrays in four biological replicates.

Results
Differentially up-regulated and down-regulated miRNAs were obtained from the respective fat depots. Seven of the most differentially expressed miRNAs were validated by qRT-PCR. The miRNA targets involved in the regulation of angiogenesis were selected by bioinformatic algorithms. We have identified 4 miRNAs that promote and stimulate ASCs differentiation into cells with endothelial cell-like phenotype through the regulation of FGFR1, NRP2, MAPK1, TGFB2, ETS1 and PTPN9.

Conclusion
In summary, the regulation of ASCs to EC differentiation (endotheliogenesis) involves a distinctive miRNA signature relying on WAT depot.
Successful treatment of patent ductus arteriosus accompanying right-sided aortic arch and aberrant left subclavian artery: a case report
Authors: Pay Levent , Calik Ali Nazmi , Akyuz Sukru , Dayi Sennur Unal 
Published: June 2022

Abstract

Background
The coexistence of a right-sided aortic arch (RAA), an aberrant left subclavian artery (ALSA), and a patent ductus arteriosus (PDA) is a rarely seen vascular ring anomaly. There is currently no general guideline consensus on the management and follow-up of this congenital defect, posing a challenge to the clinicians. At this point, the heart team plays a critical role in the management of the disease.

Case summary
In the present case, a 25-year-old male patient was presented to the outpatient clinic with dyspnoea and fatigue. A transthoracic echocardiography revealed PDA with a left-to-right shunt. To evaluate the anatomy thoroughly, a thoracic computed tomographic angiography was performed and showed PDA accompanying ALSA and RAA. The patient was evaluated by the Heart Team, and a percutaneous closure of PDA was recommended due to signs of left ventricular volume overload. The closure was successfully performed with Amplatzer vascular plug II. At follow-up, the patient was free of symptoms.

Discussion
Clinicians should be aware of the potential concomitant lesions during the diagnostic work-up. In selected patients, percutaneous closure of PDA may be the first-line therapy in experienced centres.
Non-triple helical form of type IV collagen alpha1 chain suppresses vascular endothelial-cadherin mediated cell-to-cell junctions
Authors: Togashi Kenshi , Shin Yongchol , Imamura Yasutada 
Published: June 2022

Summary
Non-triple helical collagen polypeptide α1(IV) (NTH α1(IV)) is a gene product of COL4A1 and is secreted as a polypeptide chain without the triple helix structure under physiological conditions. Studies have shown that NTH α1(IV) is up-regulated in and around vascular endothelial cells during neovascularization and vascular-like networks of in vitro angiogenesis models, suggesting its involvement in angiogenesis. In the present study, we examined the effect of NTH α1(IV) on endothelial cell-to-cell junctions, and we found that NTH α1(IV) suppressed VE-cadherin (vascular endothelial cadherin) mediated junctions and promoted cellular migration in human umbilical vein endothelial cell cultures. NTH α1(IV) is potentially a factor that induces VE-cadherin endocytosis and promotes neovascular sprouting and elongation. The possible mechanism entails endocytosis of NTH α1(IV) by its cellular receptor(s), Endo180 and/or other proteins, which results in the clearance of the cellular receptor(s) from the cell surface, thus inducing the endocytosis of VE-cadherin. Because the NC1 domain of the α1 chain of type IV collagen, called arresten, is considered an endogenous inhibitor of angiogenesis, it seems that the single polypeptide chain of NTH α1(IV) has conflicting functions.
Plant latent defense response to microbial non-pathogenic factors antagonizes compatibility
Authors: Yang Yu , Chen Shenglan , Wu Xiaoxuan , Peng Li , Vílchez Juan I , Kaushal Richa , Liu Xiaomin , Singh Sunil K , He Danxia , Yuan Fengtong , Lv Suhui , Morcillo Rafael J L , Wang Wei , Huang Weichang , Lei Mingguang , Zhu Jian-Kang , Paré Paul W , Zhang Huiming 
Published: June 2022

Abstract
Unlike microbe-associated molecular patterns (MAMPs) that are readily targeted by host immunity, microbial non-pathogenic factors (NPFs) appear negligible as they do not elicit defense. Little is known about whether and how NPFs may be monitored by hosts to control compatibility. Herein, a forward genetic screening isolated an Arabidopsis mutant with a loss of plant-rhizobacteria mutualism, leading to the disclosure of a plant latent defense response (LDR) to NPFs. The activation of LDR in the mutant, named rol1 for regulator of LDR 1, is triggered by several non-pathogenic volatile organic compounds and antagonizes plant compatibility with the beneficial bacterium Bacillus amyloliquefaciens GB03. The activation of LDR in rol1 is mediated through the prokaryotic pathway of chloroplastic lipid biosynthesis. The rol1 root microbiome showed a reduced proportion of the Bacillaceae family. We propose that, parallel to the forefront immunity to MAMPs, LDR to certain NPFs provides a hidden layer of defense for controlling compatibility with commensal or beneficial microbes.
One in 10 Virally Suppressed Persons With HIV in The Netherlands Experiences ≥10% Weight Gain After Switching to Tenofovir Alafenamide and/or Integrase Strand Transfer Inhibitor
Authors: Verburgh Myrthe L , Wit Ferdinand W N M , Boyd Anders , Verboeket Sebastiaan O , Reiss Peter , van der Valk Marc 
Published: June 2022

Abstract

Background
We determined the frequency of and factors associated with ≥10% weight gain and its metabolic effects in virally suppressed people with human immunodeficiency virus (PWH) from the Dutch national AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort switching to tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI).

Methods
We identified antiretroviral therapy–experienced but TAF/INSTI-naive PWH who switched to a TAF and/or INSTI-containing regimen while virally suppressed for &gt;12 months. Individuals with comorbidities/comedication associated with weight change were excluded. Analyses were stratified by switch to only TAF, only INSTI, or TAF + INSTI. Factors associated with ≥10% weight gain were assessed using parametric survival models. Changes in glucose, lipids, and blood pressure postswitch were modeled using mixed-effects linear regression and compared between those with and without ≥10% weight gain.

Results
Among 1544 PWH who switched to only TAF, 2629 to only INSTI, and 918 to combined TAF + INSTI, ≥10% weight gain was observed in 8.8%, 10.6%, and 14.4%, respectively. Across these groups, weight gain was more frequent in Western and sub-Saharan African females than Western males. Weight gain was also more frequent in those with weight loss ≥1 kg/year before switching, age &lt;40 years, and those discontinuing efavirenz. In those with ≥10% weight gain, 53.7% remained in the same body mass index (BMI) category, while a BMI change from normal/overweight at baseline to obesity at 24 months postswitch was seen in 13.9%, 11.7%, and 15.2% of those switching to only TAF, only INSTI, and TAF + INSTI, respectively. PWH with ≥10% weight gain showed significantly larger, but small increases in glucose, blood pressure, and lipid levels. Lipid increases were limited to those whose switch included TAF, whereas lipids decreased after switching to only INSTI.

Conclusions
Weight gain of ≥10% after switch to TAF and/or INSTI was common in virally suppressed PWH, particularly in females and those starting both drugs simultaneously. Consequent changes in metabolic parameters were, however, modest.
Revision to the nomenclatural status of Trapania (Nudibranchia: Goniodorididae)
Authors: Smirnoff Dimitri S , Donohoo Samantha A , Gosliner Terrence M 
Published: June 2022

Abstract
In a recent paper describing several new species Trapania Pruvot-Fol, 1931, a genus of dorid nudibranchs in the family Goniodorididae, one of the species named was published with two spellings of the species name. This error was introduced by copy editors after the authors had submitted the corrected proofs of the final version of the paper. Here we revise the taxonomy of this species and establish that Trapania lemnalioides is the correct name for this species.
Responsiveness of the UW Concerns About Pain Scale and UW Pain-Related Self-Efficacy Scale in Individuals With Chronic Low Back Pain
Authors: Akkarakittichoke Nipaporn , Janwantanakul Prawit , Kanlayanaphotporn Rotsalai , Jensen Mark P. 
Published: June 2022

Objectives:
The aim was to examine the responsiveness, presence of floor or ceiling effects, and minimal clinically important differences (MCIDs) for 2 new measures of pain-related catastrophizing and self-efficacy in individuals with chronic low back pain.

Methods:
A total of 183 individuals with chronic low back pain recruited from physical therapy clinics in Thailand completed the Thai versions of the 6-item University of Washington Concerns About Pain scale (T-UW-CAP6) and 6-item University of Washington Pain-Related Self-Efficacy scale (T-UW-PRSE6) at baseline and at 4 weeks follow-up. Perceived change in low back symptom was assessed at 4 weeks using a 7-point measure of Global Perceived Effect (GPE). Responsiveness of the T-UW-CAP6 and the T-UW-PRSE6 scale scores were evaluated by computing the effect sizes and standardized response means for change over time, and examining these as a function of the GPE ratings. Floor and ceiling effects were examined by evaluating the score distributions. Scale core MCIDs were estimated by computing a half a SD and SE of measurement statistics for each scale.

Results:
Responsiveness of the scales to pain treatment was supported by differences found in the mean change scores as a function of the treatment response categories. No significant floor or ceiling effects were found for either measure. Changes of 4.38 and 3.68 appeared to be the smallest change score perceived as clinical meaningful for the T-UW-CAP6 and T-UW-PRSE 6 scale scores, respectively.

Discussion:
The T-UW-CAP6 and T-UW-PRSE6 demonstrated good ability to detect perceived changes over time in patients with chronic low back pain. The MCIDs values provide a benchmark for assessing individual improvement in this clinical context.