bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 051: The Myogenic Tone Of Resistance Arteries Is Controlled By A Molecular Pathway Driven By Tgfβ Through Emilin1 And Converging On The Regulation Of Trp Channels.
Authors: Carnevale Daniela , Casaburo Manuel , De Lucia Massimiliano , Pallante Fabio , Bressan Giorgio , Lembo Giuseppe 
Published: March 2022

Emilin1 (E1) is a protein of the extracellular matrix that regulates TGFβ bioavailability through proteolysis of the proTGFβ. E1 KO mice are hypertensive, with increased TGFβ activation. As E1 is expressed in blood vessels starting from embryonic life to adulthood, is still unknown whether the E1 KO phenotype results from a developmental defect or lack of a homeostatic role in the adult. To dissect this issue, we used a conditional gene targeting approach to inactivate E1 in smooth muscle cells (VSMCs) of adult mice, by the use of floxed E1 and CreERT2 [tamoxifen (TAM) inducible Cre recombinase] under the control of the smooth muscle myosin heavy chain (Smmhc) promoter. When E1fl/fl mice carrying the Smmhc-CreERT2 were given TAM blood pressure significantly increased (124±1 vs basal condition 106±1 mmHg) as well as myogenic response in resistance arteries (16.3±0.7 vs basal condition 11.4±0.1 % at 125 mmHg).
In order to understand how E1 ablation in VSMCs could functionally determine the increase in myogenic tone, we used an ex vivo approach in resistance arteries, to target the molecular pathway that could regulate intracellular calcium fluxes, the main regulator of myogenic contraction. Experiments performed in isolated VSMCs from E1 KO as compared to WT arteries, suggested the involvement of a ROCE (receptor operated calcium entry) mechanism, whose main final molecular determinant is represented by the TRP channels, known to be regulated by a canonical PLC-DAG pathway, but also by a parallel one controlled by the growth factors signaling cascade. By exploring this pathway, we found that E1 regulates the activity of TRPC3 channels and thus of the myogenic response. The molecular pathway delineated by our studies started from the transactivation of EGFR through metalloproteinases and converged on the Src kinases that increased TRPC3 function and thus calcium entry. In particular, with an in vivo targeting of TRPC3 in E1 KO with an adenovirus carrying a dominant negative mutation, we demonstrated a rescue of the increased myogenic response of E1 KO resistance arteries.
Overall our results suggest that this pathway in VSMC, driven by TGFβ and regulated by E1, is crucial for the myogenic tone of resistance arteries and is linked to the regulation of blood pressure.
Abstract 202: Involvement of neuronal high mobility group box 1 (HMGB1) in Angiotensin II-mediated neuronal-microglial interaction
Authors: Song Chunjuan , Santisteban Monica , Zubcevic Jasenka , Raizada Mohan 
Published: March 2022

We have demonstrated that activation of microglia in the autonomic brain regions, primarily in the paraventricular nucleus (PVN), is critical in the development and establishment of hypertension. Neuroimmune synaptic communication is implicated in activating microglia and inducing neuroinflammation in many neuropathophysiological diseases. Specifically, HMGB1 secreted by neurons is a critical mediator in neuroimmune crosstalk. Thus we hypothesized that HMGB1 is a key regulator involved in microglia activation in Ang II-induced hypertension. Neuronal and microglial cells in primary culture were established for this study. Effect of Ang II on microglial movement was recorded and quantified by time-lapse microscopy and video analysis. In addition, the expression, translocation and secretion of HMGB1 in neurons were measured by qPCR, Western blot and immunocytochemistry.
Ang II treatment of neuronal-microglial co-culture resulted in a 5-fold increase of microglial migration towards neurons, which was completely abolished by treatment with 1 μM Losartan, an Ang II receptor type 1 antagonist. The presence of neurons was found to be essential for microglial movement since Ang II failed to induce these effects in the absence of neurons. Neurons express high levels of HMGB1, which was predominantly localized in the nucleus. Ang II treatment resulted in a time-dependent translocation of nuclear hMGB1 into the cytoplasm and ultimately into the medium. Both translocation and release of Ang II-induced HMGB1 was blocked by Losartan. Furthermore treatment of microglia with 500ng/ml recombinant HMGB1 caused ~2 fold increase of proinflammatory cytokines (TNF-α and IL-1β). The importance of HMGB1 is further underscored by our observation that its protein level was increased ~2 fold in the PVN but not in the nucleus of the solitary tract (NTS) or rostral ventrolateral medulla (RVLM) of the spontaneously hypertensive rats (SHR) compared with the normotensive WKY rats. Taken together, these observations suggest that Ang II primarily activates the neuronal AT1R to increase the expression, cytosolic translocation and release of HMGB1. The released HMGB1 primes microglial activation and release of cytokines, two key events in neuroinflammation in hypertension.
Abstract 217: Analysis Of Aspects Electrocardiographic, Vectorcardiographic And Echocardiographic Of Left Ventricular Hypertrophy In Resistant Hypertension
Authors: Dinamarco Nelson , Dinamarco Marileide , Moreno Heitor 
Published: March 2022

Introduction:
Resistant hypertension (RHTN) defined as the failure to reach goal BP, with at least 3 drugs including a diuretic (JNC-VII). Affects 5-30% HTN, become high risk of developing target organ damage, like LVH rasing morbi-mortality (Framingham Study). Then is necessary a better treatment plan the early diagnosis. The electrocardiogram (ECG) and the vectorcardiogram (VCG), graphic methods (GM), alone, present, in spite of high specificity, have low sensitivity compared with echocardiography (ECHO).

Objective:
Analyze ECG/VCG for LVH diagnosed by ECHO in RHTN.

Methods:
Population: 120 RHTN. Excluded diabetic, valve heart, coronary, renal diseases and obese. Study Protocol: After 06 months, between 2008 and 2011, measures BP monthly (JNC-VII) receiving directions, as well as pill counts (Taylor Method) to assess compliance. Underwent ECHO (ASE) then GM. ECG&VCG methods: ECG Criterion: Sokolow-Lyon I(SL-I):SV1+RV5(6)≥3.5mV & II(SL-II):RavL≥1.1mV; Gübner(G):SDI+RDIII≥2.5mV;Cornell(C):RavL+SV3≥2/2.8mV(woman/man);Romhilt-Estes(RE):Point Score≥5points; Perugia(P): RE or C(modify) or Strain. VCG Criterion: Mag Max QRS on Planes horizontal(HP) & frontal(FP): vector≥2mV and right saggital(rSP): vector≥1.6 mV; Defl QRS HP & rSP: angle≥ 330° & ≥150°.

Statistical Analysis:
Sensibility(SENS), accuracy(ACCU) and specificity(SPEC) to analyse GM.

Results:
Criterion Sens (%) Accu (%) Spec (%)

SL-I 27 (16/60) 61 (73/120) 93 (56/60)
G 18 (11/60) 58 (69/120) 97 (58/60)
SL-II 18 (11/60) 58 (69/120) 97 (58/60)
C 25 (15/60) 59 (71/120) 93 (56/60)
RE 32 (19/60) 58 (77/120) 95 (58/60)
P 50 (30/60) 68 (81/120) 85 (51/60)
Mag Max QRS PH 28 (17/60) 61 (73/120) 93 (56/60)
Mag Max QRS PSr 12 (07/60) 52 (62/120) 92 (55/60)
Mag Max QRS PF 25 (15/60) 57 (68/120) 88 (53/60)
Defl QRS PH 12 (07/60) 52 (62/120) 92 (55/60)
Defl QRS PSr 13 (08/60) 50 (60/120) 87 (52/60)
COMBINED* 70 (42/60) 76 (91/120) 82 (49/60)

Conclusion:
ECG: P had the best SENS & ACCU, SL-II and G both showed the best SPEC. VCG: best criteria Mag Max QRS PH. Combined criteria* using best SENS and ACCU of each GM improved SENS & ACCU demonstrated SPEC without injury to LVH in RHTN detection. Can be worn with method in a cost effectiveness ratio and in places where access is difficult to ECHO to be performed.
Abstract 229: Genetic inhibition of Notch3 protects animals against Chronic Kidney Disease.
Authors: Keuylian Zela , El Machhour Fala , Dussaule Jean-Claude , Chatziantoniou Christos 
Published: March 2022

In the present study, we show that expression of the Notch3 receptor in glomeruli is associated to the development of renal disease and that inhibition of this expression is accompanied by renoprotection.
In a model of rapidly progressive glomerulonephritis (nephrotoxic serum-induced renal disease), Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. In contrast, mice with genetic ablation of Notch3 expression (KO) were protected as they showed less proteinuria, uremia and renal inflammation. In vitro studies suggested that podocytes expressing active Notch3 acquire a migratory and pro-inflammatory phenotype. To evaluate whether inhibiting Notch3 could be of therapeutic interest, we administered antisense oligodeoxynucleotides targeting Notch3 in wild type mice concomitantly to the disease induction, whereas scrambled sequences were used as controls. Both groups of mice developed renal disease, but mice injected with Notch3 antisense were protected compared to the scrambled group, as evidenced by the decreased values of plasma urea and proteinuria. In addition, the improvement of renal function was accompanied by fewer crescent formations and less deposits of fibrin within the glomeruli, and by decreased peritubular inflammation.
These results demonstrate that abnormal activation of Notch3 in the kidneys is involved in the progression of renal disease by promoting migratory and pro-inflammatory pathways and that blocking this activation preserves renal function and structure. Inhibiting Notch3 activation could be a novel, promising approach to treat chronic renal disease.
Abstract 237: Family History Of Premature Cardiovascular Events And Total Plaque Area
Authors: Perez Hernan A , Garcia Nestor H , Spence J. Dave , Armando Luis J 
Published: March 2022

Although the positive family history for premature cardiovascular events has been considered a putative risk factor for decades, it has not been incorporated along with other established risk factors such as hyperlipidemia, hypertension, and cigarette smoking in the daily clinical practice when physicians evaluates the cardiovascular risk of a patient. One of the reason may be the presence of multiple risk factors coexisting during these evaluations.
The objective of this research was to investigate if patients with a family history of premature cardiovascular events have higher total plaque area than patients without it, in the absence of other classical risk factors.

Design and method:
Patients from the primary prevention database of Blossom DMO program were identified to have positive family history of premature cardiovascular events (FHPCVE). After apply excluding criteria (absence of any classical risk factor) 23 patients qualified. A control group was generated reaching same data in variables (blood pressure, age, body weight, LDL cholesterol), except carotid total plaque area which was reported at the end of groups formation, once both groups were formed. We used the same definition as the Framingham study (family history of <55 years in men and <65 years in women, first degree relatives) to consider a patient with FHPCVE.

Results:
The group with FHPCVE was similar to the control group. Age 59±2 sv 60±1 yo, blood pressure 126±2/75±1 mmHg vs 127±1/74±1 mmHg, body mass index, 23±1 vs 24±1 Kg/cm
2
and LDL cholesterol 116±15 vs 139±20 mg/dl. When total plaque area was determined by Doppler, patients with FHPCVE had a TPA of 49±8 mm
2
while control group 33±4 mm
2
(p<0.05). Framingham risk score were similar, while the post test for acute myocardial infarction was lower in control group (16±1% vs 20±3%, p<0.05).

Conclusions:
Our data indicates that patients with positive family history for premature cardiovascular events have larger total plaque area than patients without it, indicating enhanced risk to develop a cardiovascular event, even in the absence of other classical risk factor. Physicians should identify early and treat accordingly these patients to prevent arterial deterioration.
Abstract 270: Successful Development and Implementation of an Algorithm to Identify Resistant Hypertension in the Electronic Medical Record
Authors: Shuey Megan M , Denny Joshua C , Edwards Todd L , Brown Nancy J 
Published: March 2022

Resistant hypertension (RH) affects 8.4 to 17.4% of the hypertensive population, and is associated with an elevated risk of end-organ damage. To identify genetic or environmental factors associated with RH, we developed an algorithm to phenotype patients using electronic medical records (EMRs).
We modified a previously validated algorithm for detecting patients with RH from 158,128 adults in BioVU, a DNA databank incorporating clinical data from EMRs. We defined patients as having RH if they had a SBP>140 mmHg or a DBP>90 mmHg for at least one month while receiving at least three anti-hypertensive agents including 25 mg HCTZ or equivalent doses of another thiazide diuretic or amlodipine 5 or 10 mg, or equivalent doses of a similar calcium channel blocker. Patients could be controlled after addition of a fourth drug. Patients were defined as having controlled hypertension if they carried a diagnosis of hypertension, were taking at least one and no more than two anti-hypertensive medications, and had a SBP<135 and a DBP<90 mmHg on repeated measurement. Drug exposures were identified from electronic-prescribing tools and MedEx.
To validate the algorithm, we conducted an independent review of 150 EMRs from patients classified as having resistant or controlled hypertension. The accuracy of the algorithm was 94.7%. Among 55,477 patients with hypertension in BioVU, 14.2% met the criteria for RH. The table shows the characteristics of patients with resistant and controlled hypertension.
This study demonstrates the successful use of a phenotyping algorithm to identify subjects with RH from EMR data and provides important characteristics of patients with RH in a real-world clinical setting.
Abstract 315: Endothelial And Autonomic Dysfunctions Induced By High Fructose Intake Are Modulated By The Angiotensin Converting Enzyme (ACE) Gene Dosage
Authors: Moraes-Silva Ivana C , Souza Leandro E , Irigoyen Maria-Claudia , Casarini Dulce E 
Published: March 2022

ACE gene polymorphism may be associated with different responses to physiological and pathological stimuli. Therefore, we tested whether low, normal or high levels of ACE gene dosage influence on the effects of chronic and excessive fructose intake (F).
Male mice (22±1g) harboring 1, 2 or 3 copies of the ACE gene received F (100g/l) or tap water for 8 weeks. After this period, glucose tolerance (0-120 min after glucose load=1.5 g/Kg ip) and lipids were measured; blood pressure (BP) signals were recorded (Windaq, 4kHz), and BP variability was analyzed in frequency domain (FFT). After euthanasia, mesenteric resistance artery (MRA) was dissected out and rings were mounted in an isometric myograph (DMT,620M). MRA responses to noradrenaline (Nor; 0.1nM-1μM) and acetylcholine (Ach; 0.01nM-30μM) were studied. One-way ANOVA and p<0.05 were used for statistical analysis

F induced glucose intolerance (1 copy: 100±3 vs. F=198±5; 2 copies: 121±4 vs. F=201±8; 3 copies: 86±4 vs. F=212±5 mg/dl after 120 min) with no alterations in total cholesterol nor triglycerides. Systolic BP increased in 2 and 3-copy mice after F (1 copy: 119±2 vs. F=124±4; 2 copies: 120±3 vs. F=131±3; 3 copies: 121±3 vs. F=139±4 mmHg) and diastolic BP increased in all F-fed groups (1 copy: 80±2 vs. F=92±3; 2 copies: 83±2 vs. F=95±4; 3 copies: 84±2 vs. F=100±2 mmHg). The augment in systolic BP was significantly higher in 3-copy (17±1 mmHg) vs. 1 (6±1 mmHg) and 2-copy mice (10±1 mmHg). F also increased BP variability in all groups, with a more pronounced augment in 3-copy mice vs. other groups (1 copy: 39±3 vs. F=57±2; 2 copies: 37±2 vs. F=60±3; 3 copies: 40±3 vs. F=73±7 mmHg
2
). Additionally, the sympathetic component of BP variability (LF %) presented a similar behavior (1 copy: 5±1 vs. F=12±3; 2 copies: 6±2 vs. F=19±3; 3 copies: 7±3 vs. F=31±5 %). Ach-induced relaxation was reduced in F mice (1 copy: 78 vs. F=58; 2 copies: 76 vs. F=47; 3 copies: 73 vs. F=36 %) and a hyperreactivity to Nor was also observed (1 copy: 92 vs. F=170; 2 copies: 107 vs. F=190; 3 copies: 101 vs. F=214 %). In both responses, 3-copy mice were significantly different than the other groups.

ACE gene dosage seems to modulate the magnitude of MRA and autonomic dysfunctions caused by F consumption, inducing a more increased cardiovascular risk for 3-copy mice.
Abstract 403: MicroRNA-21 Ablation Exacerbates Aldosterone-mediated Cardiac Inflammation, Fibrosis, Hypertrophy and Dysfunction
Authors: Syed Maryam , Ball Jana P , Mathis Keisa W , Hall Michael E , Ryan Michael J , Rothenberg Marc E , Romero Damian G 
Published: March 2022

Excess aldosterone (ALDO) causes hypertension and cardiac hypertrophy, inflammation and fibrosis that lead to cardiac dysfunction. We reported that ALDO/SALT treatment increases left ventricle miR-21 expression after 2 weeks of treatment, and the elevation persists for up to 8 weeks. We aim to study the role of genetic ablation of miR-21 in ALDO/SALT-mediated cardiac inflammation, fibrosis, hypertrophy and function.
Eight-week old uninephrectomized male miR-21 knockout (miR21KO) or wild-type (WT) mice were assigned to 4 groups (N=12/grp): WT-Control, WT-ALDO/SALT, miR21KO-Control and miR21KO-ALDO/SALT. Animals were treated for 8 weeks. ALDO (0.15 μg/h) or vehicle (PEG 300) was administered by osmotic minipump. SALT (1.0% NaCl + 0.3% KCl) was administered in tap water. Cardiac function was determined by echocardiography. Tissues were weighed and standardized to body weight. mRNA levels were quantified by qPCR. Another set of animals (N=12/grp) was implanted with carotid artery catheters for conscious MAP determination.

ALDO/SALT-mediated cardiac dysfunction was exacerbated in miR21KO mice (EF: 38.0 ± 2.0 vs. 43.0 ± 4.1 %,
p
<0.05) compared with WT mice (EF: 50.0 ± 3.7 vs. 54.7 ± 3.1 %, NS). ALDO/SALT-mediated cardiac hypertrophy was exacerbated in miR21KO mice compared with WT mice (ALDO-SALT/control: 1.30 ± 0.04
vs
. 1.18 ± 0.02,
p
<0.05).

Fibrosis marker connective tissue growth factor (Ctgf) mRNA expression remained elevated by ALDO/SALT only in miR21KO mice (7.22 ± 1.96 fold change
vs
. control,
p
<0.05). Similar results were observed with collagen I and fibronectin. Inflammation marker Serpine1 (PAI-1) mRNA expression was upregulated by ALDO/SALT only in miR21KO mice (3.11 ± 0.54 fold change
vs
. control,
p
<0.05).

Despite the exacerbation in cardiac dysfunction, hypertrophy, and fibrosis and inflammation markers expression in miR21KO mice, ALDO/SALT raised MAP to similar levels in both strains (WT: 139 ± 9
vs
. 106 ± 2 mm Hg,
p
<0.05; miR21KO: 142 ± 8
vs
. 114 ± 4,
p
< 0.05).

These results show that miR-21 ablation exacerbates ALDO/SALT-mediated cardiac inflammation, fibrosis, hypertrophy and dysfunction independently of blood pressure suggesting that therapies that increase cardiac levels of miR-21 may benefit patients with primary aldosteronism.
Abstract 406: Direct Angiotensin AT2-Receptor Stimulation Modifies T-Cell Differentiation
Authors: Sehnert Bettina , Valero-Esquitino Veronica , Cirera-Salinas Daniel , Lucht Kristin , Pascual Anna , Curato Caterina , Voll Reinhard , Unger Thomas , Steckelings Ulrike M 
Published: March 2022

Angiotensin II is known to activate T-cells via the AT1-receptor. T-cells also possess AT2-receptors (AT2Rs). However, the functional role of AT2Rs in T-cells has not been investigated.
This study tested the hypothesis that AT2R stimulation modulates T helper (Th) cell differentiation. For this purpose, naïve T-cells were isolated from spleen and lymph nodes of C57BL/6 mice, sorted, polarized in vitro under Th0, Th1, Th17 and regulatory T-cell (Treg) conditions and simultaneously treated with the AT2R agonist C21 (1μM) or vehicle for 4 days.
24 hours after the last treatment, expression of cytokines characteristic for pro-inflammatory Th1 cells (IFNγ) and Th17 cells (IL-17), or anti-inflammatory Treg (FoxP3) were determined on mRNA (qRT-PCR) and protein (FACS analysis) level.
AT2R stimulation during polarization of naïve T-cells decreased mRNA levels of IFNγ (in TH1 polarized T-cells: 2.2±0.4x105 [vehicle] versus 0.1±0.001x105 [C21] fold increase; p<0.05), IL-17 (in TH17 polarized T-cells; 572.1±149.0 [vehicle] versus 296.1±54.4 [C21] fold increase; p<0.05) and increased mRNA levels FoxP3 (in Treg polarized T-cells: 101.9±16.1 [vehicle] versus 342.5±12.4 [C21] fold increase; p<0.05).
Similar results were obtained for protein expression of IFNγ (6.5±0.5x105 [vehicle] versus 4.0±0.7x105 [C21] cells; p<0.05), IL-17 (1.2±0.1x105 [vehicle] versus 0.9±0.1x105 [C21] cells; p=0.06 and FoxP3 (1.5±0.5x105 [vehicle] versus 3.7±0.6x105 [C21] cells; p<0.05).
From our data we conclude that AT2R stimulation modifies T-cell differentiation resulting in a composition of T-cell subsets with less pronounced pro-inflammatory properties.
Abstract 417: Correlation Between The Mass Of The Left Ventricle By Echocardiogram And The Electrocardiographic And Vectorcardiographic Criteria In Left Ventricular Hypertrophy In Patients With Resistant Hypertension.
Authors: Dinamarco Nelson , Dinamarco Marileide , Moreno Heitor 
Published: March 2022

The difficult of most of patients in access the echocardiogram (ECHO) diagnosis services are common in small cities located far away from reference towns centers. Graphics methods (GM) , like electrocardiogram (ECG) and vectorcardiogram (VCG), have high sensibility but low specificity in detect LVH. The ECHO diagnosis criterion of LVH based on indexed left ventricular mass (LVMI), is usual and used now a days beside other methods like Nuclear Magnetic Ressonance.

Objectives:
Evaluate LVMI correlation with ECG and VCG criteria in patients with RHTN.

Population:
120 RHTN patients were evaluated. Excluded patients with diseases: diabetes, valve heart, coronary, Chagas, renal, obese and excentric LVH.

Study Protocol:
After 06 months, between 2008& 2011, measures BP monthly following the technique (JNC-VII) and receive directions, as well as pill counts (the method of Taylor) to assess compliance. Underwent echocardiography, following the recommendations of the ASE, then ECG and VCG. Formula to calculate LVMI : LVMI = 0,8 x{1.04x [(SIVD + DDVE + PPVED)3 - (DDVE)3]} + 0,6 g/(M-60) x 0,01 + H) ECG and VCG criteria to detect LVH: ECG Criterion: Sokolow-Lyon I(SL-I):SV1+RV5(6)≥3.5mV & II(SL-II):RavL≥1.1mV; Gübner(G):SDI+RDIII≥2.5mV; Cornell(C):RavL+SV3≥2/2.8mV(woman/man); Romhilt-Estes(RE):Point Score≥5points; Perugia(P): RE or C(modify) or Strain. VCG Criterion: Mag Max QRS on Planes horizontal(HP) & frontal(FP): vector≥2mV and right saggital(rSP): vector≥1.6 mV; Defl QRS HP & rSP: angle≥ 330° & ≥150°.

Statistical Analysis:
The correlations were obtained using the Pearson’s correlation formula and the is considered a good correlation values above 50%, and excellent correlation values above 70%. Values less than 50% are considered weak correlation. Results are expressed as mean and standard deviation, and relative values in percentage.

Results:
Criterion Correlation R

SL- I 0.49
G 0.42
SL-II 0.50
C 0.49
RE 0.51
Mag Max QRS HP 0,59
Mag Max QRS rSP 0.60
Mag Max QRS FP 0.51
Defl QRS PH 0.33
Defl QRS rSP 0.56

Conclusion:
The better correlation between LVMI and ECG criterion was Romhilt-Estes and the better for the VCG was Mag Max QRS HP. The VCG had the best correlation. Considered a good alternative to estimate the LVMI.