bluuebunny/crossref_metadata_2025_split huggingface dataset:
O64 ENHANCED EXPRESSION AND MEDIAL LAYER LOCALIZATION OF ELASTASE-2, AN ANGIOTENSIN ENZYME: IMPACT ON ABDOMINAL AORTIC ANEURYSM HALLMARKS IN MICE
Authors: Mestriner Fabiola , Dugaich Vinicius Flora , Dantas Pedro Bruch , Kovacs Henrique , Ribeiro Mauricio Serra , Becari Christiane 
Published: September 2024

Abdominal aortic aneurysm (AAA) is a pathological dilation of the abdominal aorta that can lead to death, with no pharmacological treatment available other than repair surgery. Continuous angiotensinII (AngII) infusion induces AAA in mice. Elastase-2 (ELA-2), a chymotrypsin-serine protease and an elastase family member, acts as an AngII enzyme in arteries and contributes to resistance arteries and vascular remodeling in animal models. Therefore, ELA-2 is a potential factor in AAA formation and/or development. We sought to investigate the expression and localization of ELA-2 in AAA-induced mice.

Methods:
Male wild-type (C57bl/6,WT) and ELA-2knockout (CELA-2aTm1Bdr; ELA-2KO) mice treated with saline (WT+Sal n=10, ELA-2KO+Sal, n=9) or AngII (1.500ng/kg/min, WT+AngII n=8, ELA-2KO+AngII n=8) for twenty-eight days by subcutaneously mini-pumps infusion. Vascular ultrasonography (US, Vevo2100) analyzed, before and after treatment, aortic expansion index, aortic systolic and diastolic diameter parameters. The immunofluorescence for ELA-2, aorta layer, and histologic staining to collagen, elastin, and fibrosis was analyzed. A correlation between ELA-2 and US was done.

Results:
WT+AngII mice developed AAA, and ELA-2KO mice did not have AAA by infusion of Ang II. Aorta ELA-2 expression up-regulated in WT-AngII vs. WT+Sal (p=0.0001). Aortic systolic diameter increased in the WT+AngII vs WT+Sal (0.8vs.1.5 mm, p<0.0001). Aortic diastolic diameter increases in the WT+AngII vs WT+Sal (1.2 vs.0.6 mm, p<0.0001). The aortic expansion index decreases in WT+Ang II vs WT+Sal (11.4 vs.17.1%, p=0.0008). WT+AngII aorta has higher collagen deposition and fibrosis and lower elastin than WT+Saline (p=0.001). ELA-2KO+AngII vs. ELA-2KO+SAL showed no difference in elastin, collagen, and fibrosis. The analyzed parameters characteristic of AAA showed a positive correlation with ELA-2 in aorta middle layer in WT+AngII, where AAA develops.

Conclusion:
ELA-2 expression is up-regulated in AAA mice’s aorta and may contribute to developing aneurysms. ELA-2KO might be less susceptible to developing AAA induced by AngII infusion. Therefore, ELA-2 plays a significant role in AAA pathophysiology and could be a potential target for therapeutic treatment to prevent AAA development.
O39 IMPACT OF UROMODULIN CONCENTRATION ON RENAL AND HAEMODYNAMIC PARAMETERS IN A BLACK AFRICAN COMMUNITY WITH A HIGH PREVALENCE OF HYPERTENSION
Authors: Peterson Vernice , Charles Aaliah , Reddy Manishka , Gomes Monica , Du Toit Wessel , Woodiwiss Angela 
Published: September 2024

Background and Objective:
The burden of hypertension (HTN) and related comorbidities disproportionately affects developing countries like South Africa, particularly in urban populations of African ancestry. This demographic exhibits a volume-dependent form of HTN that is resistant to antihypertensive drugs that target the renin-angiotensin-aldosterone system. Renal fluid retention or abnormalities may cause HTN in this group, thus the need to investigate various nephron components for a better understanding. Uromodulin is a potential biomarker for renal function and tubular reserve. However, the relationship with renal function, haemodynamic parameters and HTN in a Black African population is unknown. Therefore, the aim of this study was to explore the relationship between urinary uromodulin concentration and renal as well as haemodynamic parameters in a Black African community with a high prevalence of volume-dependent HTN.

Methods:
Systemic haemodynamics (central pressures [SphygmoCor] and echocardiographic aortic velocity and diameter measurements in the outflow tract), urinary uromodulin concentrations (ELISA assay) and renal function (creatinine clearance from 24-hour urine collections [n=370]) were determined in a Black African community (n=397).

Results:
No relationships between urinary uromodulin concentrations and age, body mass index, blood pressure or hypertension were noted. However, urinary uromodulin concentrations were higher in females than males, even after adjusting for several confounders (p=0.0007). Although urinary uromodulin concentrations were unrelated to renal function, an inverse relationship with stroke volume (SV) was observed (p=0.0023). The inverse relationship between SV and urinary uromodulin concentration was independent of confounders and present in hypertensives (p=0.007) but not normotensives (p=0.43). The hypertensives were noted to have a higher SV than the normotensives (p=0.047).

Conclusion:
In a Black African community sample with a high prevalence of volume-dependent primary hypertension, urinary uromodulin was inversely related to SV, particularly in participants with hypertension. These data suggest the need to investigate the mechanisms linking urinary uromodulin to haemodynamic parameters to identify novel pathways to target for better treatment strategies in hypertension.
O41 CLINICAL INERTIA IN PATIENTS WITH RESISTANT HYPERTENSION CONTROLLED BY AMBULATORY BLOOD PRESSURE MEASUREMENTS
Authors: Zanuzzi Matias , Bernabeu Francisco , Cornavaca Teresita , Romero Cesar 
Published: September 2024

Background and objective:
Uncontrolled hypertension, especially among high cardiovascular risk patients like those with resistant hypertension (r-HTN), remains a significant public health concern. Clinical inertia, the failure to initiate or intensify therapy, is a major contributor to uncontrolled hypertension, including in r-HTN patients. We aimed to assess the prevalence of clinical inertia and its associated characteristics in r-HTN patients.

Methods:
A retrospective analysis of consecutive Ambulatory Blood Pressure Measurements (ABPM) in patients between August 2016 and August 2023 in a Cordoba, Argentina tertiary center was performed. r-HTN was defined by ABPM when optimal or best-tolerated doses of three drugs failed to control blood pressure (BP) or the patient received four or more drugs regardless of BP control. Therapeutic inertia was diagnosed when uncontrolled BP persisted without pharmacological changes in the subsequent visit to the ABPM. Failure to exclude secondary causes of hypertension constituted diagnostic inertia.

Results:
168 patients were included; mean age 66 years (Range 33-87), 55% females. r-HTN prevalence was 31.5% (53/168). Overall uncontrolled BP was 61.9% (104/168), with r-HTN patients exhibiting higher rates (75% vs 55.7%; p=0.014) of uncontrolled BP. Therapeutic inertia was 28.6% (48/168), being more frequent in r-HTN patients (41.5% vs 22.6%; p=0.012). Patients with therapeutic inertia had a greater number of comorbidities (1.2 ± 1.0 vs. 0.7 ± 1.0; p=0.003), diabetes (52% vs. 33%; p=0.024), more anti-hypertensive drugs (3.4 ± 0.6 vs. 3.2 ± 0.7; p=0.039), and higher BP values during ABPM. In a multiple regression model, only SBP24 independently predicted therapeutic inertia (p<0.01). Diagnostic inertia was 86.3% (145/168), lower in r-HTN patients (75.5% vs 91.3%; p=0.006). Patients with diagnostic inertia had lower BMI (30.0 ± 4.7 vs 31.2 ± 9.8; p=0.043), coronary artery disease (10% vs 26%; p=0.034), and fewer anti-HTN drugs (3.2 ± 0.6 vs 3.7 ± 0.9; p=0.002).

Conclusion:
Clinical inertia in resistant hypertension patients is highly prevalent, emphasizing the necessity of improving inertia to enhance blood pressure control and patient outcomes.

Table 2.- Clinical variables associated with the diagnosis of therapeutical inertia.
O47 THE ROLE OF IL-33 AND ST2 IN THE MODULATION OF TARGET ORGAN DAMAGE IN ANGIOTENSIN II-DEPENDENT HYPERTENSION
Authors: Saju Blessy , Nosalski Ryszard , Booth Emma , Guzik Tomasz 
Published: September 2024

Introduction:
Hypertension is associated with a chronic inflammatory state and aberrant immune system activity. Interleukin-33/suppression of tumorigenicity 2 (IL-33/ST2) signalling axis is important in the modulation of atherosclerosis and cardiovascular fibrosis. We aimed to evaluate the modulation of IL-33 and ST2 in hypertensive mouse models and patients.

Methods and Results:
Hypertension was induced by a 14-day infusion of Ang-II (490ng/min/kg) in 12-week-old WT C57BL/6, ST2KO, IL33KO mice. IL-33 and ST2 mRNA and protein were evaluated using qPCR and Western blot in WT mice. Ang II-infusion significantly increased IL-33 and ST2 protein expression in target organs related to hypertension, particularly the aorta (1.0±0.1 vs 2.8±0.2, p<0.0001, and 0.963±0.068 vs 2.094±0.231, p=0.002, respectively). Further, mRNA expression of IL-33 and ST2 was elevated in hypertensive aortas when compared with control (1.0±0.053 vs 1.76±0.271, p=0.0185 and 1.0±0.039 vs 1.978±0.221, p=0.0039, respectively). IHC from WT mice illustrated the localisation of IL-33 and ST2 in Ang-II aortas in ECs and SMCs. Further in human hypertensive mammary arteries, the localisation was. In-vivo, IL33KO and ST2KO mice showed no altered BP at baseline or after 14 days of Ang-II compared to WT littermates. ST2KO Ang-II mice showed protection against endothelial dysfunction compared to WT Ang-II mice through isometric tension studies (p=0.0317). Additionally, Ang-II-induced IL33KO and ST2KO mice worsen cardiac fibrosis compared to WT littermates (p=0.0005,p<0.0001, respectively).

Conclusion:
Both IL-33 and its receptor, ST2 are increased in the vascular and perivascular tissues in hypertension. Additionally, the IL-33/ST2 axis has a role in regulating cardiac fibrosis.
O48 CHRONIC EXPOSURE TO POLLUTED URBAN AIR ALTERS MOUSE SYSTEMIC AND TISSUE-SPECIFIC COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM (RAS)
Authors: Dominici Fernando , Pardo Jorge Narvaez , Freire Agustina , Barrales Benjamin , Buccholz Bruno , Gironacci Mariela , Magnani Natalia , Evelson Pablo 
Published: September 2024

Background and Objective:
Chronic exposure to air pollution induces pulmonary, cardiovascular, and renal diseases. In the current study, we investigated the hypothesis that postulates that a dysregulation of the RAS may contribute to these pathologies.

Methods:
Male Balb/C mice were exposed to urban air from Buenos Aires City, in whole-body exposure chambers for 14 weeks. Control animals were exposed to filtered air. The levels of main RAS components including angiotensin-converting enzyme (ACE) and ACE2; AT1, AT2, and Mas receptors (R) were determined in mouse lungs, kidneys, and heart, through western blotting (WB) and RT-qPCR, respectively. The tissue content of cytokine mARN was determined by RT-qPCR. The tissue content of nitrotyrosine and 4-hydroxynonenal (4-HNE) levels, were determined by WB. Circulating angiotensin (Ang) II levels were determined by radioimmunoassay. Systolic blood pressure was measured by the tail-cuff method.

Results:
Exposure to air pollution resulted in a) Increased levels of ACE and AT1R mRNA in the lungs and augmented the abundance markers of inflammation (TNF-α, IL-6, and IL-1β) and oxidative stress (nitrotyrosine and 4-HNE) in this tissue, b) increased levels of MasR mRNA (all analyzed tissues) and MasR protein levels (lungs and heart), c) upregulated mRNA and protein abundance of cardiac and renal AT2Rs, and d) Increased levels of circulating Ang II and e) augmented systolic blood pressure.

Conclusions:
Our findings indicate that chronic exposure to air pollution alters the expression of both tissue and systemic components of the RAS. Since both AT2R and MasRs have been shown to participate in tissue-repair mechanisms, the upregulation of these receptors detected in mouse lungs, heart, and kidney after chronic exposure to polluted urban air could represent a mechanism of tissue protection against damage induced by air pollution.
O51 EXPLORING GENETIC BASIS OF RESISTANT HYPERTENSION IN EUROPEAN AND AFRICAN POPULATIONS
Authors: Lorenzo Oscar , Garcés Dr Carmen , Pérez-Nadador Iris , Fokkens Hannah , Abrahams-October Zainonesa , Sharma Jyoti , Cortés Marcelino , Pello Ana , Tuñon José , Apalata T , Johnson Rabia 
Published: September 2024

Background:
Approximately 15% of hypertensive (HTN) patients experience resistant hypertension (RHTN) despite the use of ≥ 3 antihypertensive agents (diuretic and blockers of calcium channels and the renin-angiotensin system) at maximum tolerated doses. Intriguingly, genetic variation and alterations in gene content may contribute to RHTN developing.

Aim:
To comprehend the genetic determinants of RHTN across diverse ethnicities, this study has compared the gene content and presence of single nucleotide variants (SNVs) in RHTN versus controlled-HTN and normotensive participants within European (EU) and South African (SA) populations.

Methods:
Blood-isolated DNA was collected from 6 participants from EU and 15 from SA. Patients were categorized into 3 groups: RHTN (SA; n=5 and EU; n=6), controlled-HTN (n=5), and normotensive (n=5). DNA was used for Whole Exome Sequencing (WES) analysis. Library preparation and exome capture were done using the MGIEasy Universal DNA library prep and exome capture v5 probe set. Mapping was done using GATK, and the variant calling and annotation were performed using with the SIFT tool and R software.

Results:
PCA analysis and minimum spanning network showed significant genetic diversity between EU and SA populations. WES identified 16 common genes, with 207 and 220 genes associated to RHTN in EU and SA, respectively. These genes were involved in cardiac electrical conduction (K+/Ca++ channels) and lipid storage (HDL deficiency). In addition, SNV within pharmacogenes in SA (CYP2D6, CYP3A5, APOE) and EU (ADD1) cohorts alongside genes linked to disease susceptibility (RyR1 and PPP1CA) were also identified. RyR1 and PPP1CA are both implicated in HTN development through their roles in calcium signaling and vascular smooth muscle cell function. Noteworthy, two SNVs, rs121918006 and rs61732908, within RyR1 were previously linked to HTN.

Conclusions:
The large genetic differences observed between EU and SA subjects highlight the diverse genetic landscape surrounding RHTN. Notably, specific genes and their related SNV that associated to cardiac calcium channels and lipid storage could show potential targets for personalized therapeutic intervention.
Scientific Session 15: Exploring Novel Therapeutic Approaches to Kidney Disease
O57 NOCTURNAL BLOOD PRESSURE FLUCTUATION AND DIPPING PATTERNS IN PATIENTS WITH SEVERE OBSTRUCTIVE SLEEP APNOEA
Authors: Patzak Andreas , Bothe Tomas Lucca , Küchler Gert 
Published: September 2024

Background and Objective:
Nighttime blood pressure (BP) is important for diagnosis of hypertension and for cardiovascular risk stratification. Remarkably, a reverse dipping pattern is a strong and independent predictor of overall mortality and major adverse cardiovascular events. Therefore, the further clarification of the underlying mechanisms of non- and reverse dipping is crucial to improve the treatment of patients with nighttime hypertension.

Methods:
We investigated 97 patients with suspected obstructive sleep apnoea (OSA, AHI >30) using standard polysomnography and continuous BP measurement based on the pulse-transit-time method (SOMNOscreen Plus®, SOMNOmedics). Frequency and amplitude of fluctuations in systolic BP following sleep disturbances (OSA) were investigated.

Results:
Apnoeic events went along with transient increases of BP. In some cases, systolic BP did not reach the value before the apnoea but increased over time. We defined elevations of the systolic BP baseline by >10 mmHg with a duration of >10 min as BP superpositions. The superposition periods were also characterized by increased BP amplitudes with peak values of BP up to 220 mmHg. Superposition occurred in 48 patients. Further, 65% of the OSA patients were identified as non-dippers. However, nearly all the patients with superposition (98%) were identified to have non-dipper or reverse dipper patterns.

Conclusions:
Our study strongly suggests that non-dipping and reverse dipping in patients with severe OSA are causally linked to OSA related BP fluctuations. Further, continuous elevations in SBP baseline (superpositions) result in extreme BP values. This behaviour with high BP peaks may be contributing to the increased mortality in patients with reverse dipping. Therefore, identification and adequate treatment of patients with reverse dipping reduces the cardiovascular risk and may prolong their life.
O59 INFLUENCE OF CIRCADIAN BLOOD PRESSURE PATTERN ON RIGHT VENTRICULAR STRUCTURE AND FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSIION
Authors: Rekhviashvili Ann , Kvitsiani Arsen , Paposhvili Kakha 
Published: September 2024

Background and Objective:
It is well proven, that arterial hypertension affects left side of the heart and causes its remodeling and functional changes. Since heart works as a unit and has ventricular interdependence, aim of the study was to assess influence of hypertension and circadian blood pressure (BP) profile on a right ventricular structure and function.

Methods:
75 hypertensive patients (57.13±7.27 y/o) and 25 normotensive control subjects (57.56±7.55 y/o) were involved in a study. All of them were males without history of coronary artery disease, cerebrovascular or peripheral artery disease, obstructive lung disease, significant valvular heart disease or heart failure. All of them were either lifetime nonsmokers, or stopped smoking more than 5 years. All the patients underwent to 24-hour ambulatory BP monitoring and heart ultrasound with tissue doppler imaging.

Results:
Hypertensive patients with dipper circadian BP profile had higher TAPSE (19±1.586 vs 17.708±2.857; P<0.05), higher right ventricular ejection fraction (55.103±4.597 vs 47.829±14.605; P<0,005) and lower right ventricular outflow tract diameter (29.985±3.932 vs 32.639±3.510; P<0/05). None of the echo parameters were different between normotensive subjects with different circadian BP pattern. Trans tricuspid valve early diastolic (E) and late diastolic (A) peak velocities were significantly lower in hypertensive patients (1.416±0.130 vs 0.897±1.49; P<0.005). Hence, non-dipper hypertensives had significantly lower tricuspid E/A ratio in comparison with dippers (0.812±0.094 vs 1.048±0.101; P<0.00001). Interventricular septum and posterior wall diameters were higher in non-dipper hypertensives (1.134±0.131 vs. 1.322±0.138; P<0.00001 and 1.072±0.175 vs. 1.254±0.135; P<0.001; respectively).

Conclusion:
Study data show increased interdependence between two ventricles. Patients with arterial hypertension have systole-diastolic dysfunction, which especially well is present in patients with non-dipper circadian BP profile.
O62 DEGREE OF HYPERTENSION CONTROL IN ABORIGINAL AND NON-ABORIGINE POPULATIONS OF A CITY IN NORTHERN ARGENTINE
Authors: Romano José René , YEGROS Olga , Fernandez Anair , Gomez Osmar A. Acosta , Eileen Ynfante Maira , Marañon Rodrigo O. 
Published: September 2024

High blood pressure is a widely prevalent pathology in the province of Formosa, 52% according to the latest Argentine national survey 2019, so we do not have current data, it was decided to carry out a survey that evaluates blood pressure, arterial stiffness and peripheral resistance. To evaluate how these variables are presented in 2 populations of our city, one of the general population and the other of an indigenous ethnic group of the province called Toba that lives in a neighborhood of this city.

Materials and methods:
data collection was carried out on patients in 3 institutions, all of which were public, with a prior diagnosis of the disease made by a health professional, in the Central Hospital of Formosa, the interdistrict hospital Evita, and the center of primary care in the Nam Qom neighborhood of Formosa. during a period of 1 month The pressure was taken by validated blood pressure monitors as well as central aortic pressure and peripheral resistance. by a Tel O Graph brand team. The data were analyzed Statistix 10.0.

Results:
80 patients, 20 from the ethnic group and 20 from the general population, 62% women, age was 52 years in the general hospital (hg) and 54 in the health center (cs), systolic blood pressure was 129 1/2 and 82 1/2 diastolic, in cs 121 and 83. The central aortic velocity was 7.76 on average and the peripheral resistance 18.62 in the hc - in the cs 6.54 and 18.6. smoking habit, 45 and 25% respectively.
The control was 87% in the BP in the hc and 75% in the cs population.

Conclusions:
Differences were found: a lower prevalence of uncontrolled hypertension than in the general population and in terms of VOP and peripheral resistance we were able to find a difference in favor of the CS population, and also in the degree of control of hypertensive patients in the same trend.
O67 URINARY PROTEOMIC PROFILING REVEALS MOLECULAR CUES UNDERLYING HIGHER HYPERTENSION SUSCEPTIBILITY IN BLACKS THAN WHITES
Authors: An Dewei , Martens Dries , Mokwatsi Gontse , Yu Yu-Ling , Chori Babangida , Latosinska Agnieszka , Mayer Gert , Kruger Ruan , Mels Catharina , Delles Christian , Stolarz-Skrzypek Katarzyna , Nawrot Tim , Li Yan , Mischak Harald , Staessen Jan 
Published: September 2024

Background and Objective:
Compared with Whites, Blacks are more prone to hypertension and salt-sensitivity. The objective was to investigate whether sequenced urinary peptide fragments derived from proteins with a key role in cardiovascular or renal structure or function have different levels in sub-Saharan Blacks compared with Whites.

Methods:
This individual-participant meta-analysis included individuals enrolled in African-PREDICT (476 Blacks and 483 Whites), FLEMENGHO (720 Whites), PROVALID-Austria (467 Whites) and UPRIGHT-HTM (106 Nigerian Blacks and 61 Polish and Slovenian Whites). Urinary peptides were quantified by capillary electrophoresis combined with mass spectrometry.

Results:
Among 2313 participants (49.7% women), median age was 40.9 years. Of 513 urinary peptides with 70% prevalence, 300 had Bonferroni-corrected significantly different levels among Black and White South Africans sharing the same environment. Analyses contrasting 582 Blacks vs 1731 Whites, sub-Saharan Blacks (582) vs European Whites (1248) replicated the findings. Combining these results with information from public databases, we identified COL4A1, COL4A2, CD99, FAT1, FGA, FXYD2, MGP, MYOCD, PCDH7, PROC, and UMOD as most likely candidates underlying the different susceptibility to hypertension and salt sensitivity between Blacks and Whites. The most relevant enriched pathways were related to hemostasis, platelet activity, collagens and biology of the extracellular matrix, and protein digestion and absorption. Disease Ontology terms comprised small-vessel disease and coronary and macrovascular atherosclerotic disease.

Conclusions:
MGP and MYOCD being involved in cardiovascular function, FGA in clot formation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major component of the glomerular basement membrane are proteins deserving further exploration in molecular and human studies as potential targets for intervention to reduce the excess hypertension risk and associated complications in Blacks.