bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-BPC11-5: INCIDENCE OF CLINICAL HYPERTENSION IN YOUNG TRANSGENDER PEOPLE AFTER A FIVE-YEAR FOLLOW-UP: ASSOCIATION WITH GENDER-AFFIRMING HORMONAL THERAPY
Authors: Hernandez-Lazaro Alba , de Leon-Durango Ricardo , Rios-Gomez Carlos , Santana-Ojeda Borja , Perez-Rivero Jennifer Maria , Fernandez-Trujillo-Comenge Paula Maria , Santana-Suarez Ana Delia , Gonzalez-Diaz Paula , Arnas-Leon Claudia , Acosta-Calero Carmen , Perdomo-Herrera Esperanza , Kuzior Agnieszka , Sanchez-Bacaicoa Maria del Sol , Perez-Garcia Maria del Pino , Martinez-Martin Francisco Javier 
Published: January 2023

Introduction and Objective:
There is a paucity of data on the long-term cardiovascular side effects of hormonal therapy in transgender people. The most overlooked issue is the cardiovascular risk associated with the use of androgen blockers. While some short-term data on blood pressure effects of gender-affirming hormonal therapy are available, the risk of hypertension development is unknown. We sought to assess this risk in our transgender patients.

Design and Methods:
Retrospective analysis of the clinical records of consecutive transgender patients who began hormonal therapy in our Outpatient Gender Identity Clinic with < 30 years of age and have a follow-up of at least 5 years. Patients who had office sitting BP > 140/90 mmHg at least twice, had an ABPM or systematic HBPM register with > 135/85 mmHg or were taking antihypertensive medication were diagnosed with hypertension. Mediation analyses with weight increase as mediator were performed post-hoc to quantify its relative contribution to the increase in blood pressure. Patients who were already living with hypertension at the onset of hormonal therapy, withdrew from it or switched androgen blockers were excluded. All subjects gave informed consent.

Results:
129 transgender women treated with estradiol and 153 transgender men treated with testosterone were included. Their onset and 5-year follow-up age, blood pressure and body weight are shown in the Table (women are stratified by type of androgen blocker) along with the incidence of hypertension. The increase in body weight was strongly correlated with the SBP increase (Spearman's r: 0.361, p < 0.001). Mediation analyses showed that 31.2% - 42.3% (95% CI) of the SBP increase was mediated by body weight increase but the rest was body weight-independent.

Conclusions:
The annual incidence of hypertension in young transgender men (1.17%) seems comparable to that of the general population, but in young transgender women the choice of androgen blocker has a remarkable effect on the incidence of hypertension, with apparent protective effect of spironolactone but a striking risk increase with cyproterone acetate (close to 5% yearly). Taken together with the known risks of this drug (meningioma, depression, low libido, liver toxicity, thrombosis…), the use of cyproterone acetate for this indication should be reconsidered. Body weight increase is undoubtedly related to the increase of BP transgender people on gender-affirming hormone therapy but is probably not the main factor.
PS-BPP01-3: DIFFERENTIAL ASSOCIATION OF CIRCULATING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 WITH THE SUBCLINICAL CEREBRAL SMALL VESSEL DISEASE AND INTRACRANIAL ARTERY STENOSIS
Authors: Kunimura Ayako , Yano Yuichiro , Torii Sayuki , Kondo Keiko , Hisamatsu Takashi , Kadota Aya , Fujiyoshi Akira , Okamura Tomonori , Watanabe Yoshiyuki , Shiino Akihiko , Nozaki Kazuhiko , Ueshima Hirotsugu , Miura Katsuyuki 
Published: January 2023

Background and aims:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low density lipoprotein cholesterol (LDL C) and incident cardiovascular disease, including stroke. However, how PCSK9 work on developing stroke is not fully elucidated. In this study we assessed the association of circulating PCSK9 levels with subclinical cerebrovascular disease, including cerebral small vessel diseases (CSVD) and intracranial artery stenosis (ICAS), in a general population.

Methods:
In community dwelling Japanese men (n = 526) aged 46–82 years, without a history of lipid lowering medications or cardiovascular disease, we assessed the associations of serum PCSK9 levels with CSVD and ICAS using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity, cerebral microbleeds. Multivariable Poisson regression with robust error variance was performed to estimate the relative risk (RR) and 95% confidence interval (CI) of the serum PCSK9 levels for the presence of CSVD and ICAS. Additionally, ordinal logistic regression was performed to estimate odds ratio (OR) and 95% CI for ICAS, with graded detectable stenosis, mild (1%-50%) and severe (> 50%).

Results:
The average (standard deviation: SD) age at baseline and median (interquartile range) PCSK9 were 68 (9) years and 240 (205 - 291) ng/mL, respectively. After multivariable adjustment including traditional cardiovascular risk factors (e.g., LDL C), a 1- SD increase of PCSK9 levels was associated with ICAS (adjusted RR 1.18, 95% CI 1.02 - 1.37), and the ordinal logistic regression model also showed a similar association (adjusted OR 1.31, 95% CI 1.04 - 1.64). However, there was no significant association between serum PCSK9 levels and CSVD.

Conclusions:
Higher circulating PCSK9 level was associated with the higher prevalence of ICAS but not with CSVD, and the association was independent of traditional cardiovascular risk factors including LDL-C. The results of this study imply the direct and independent association of PCSK9 with cerebral atherosclerotic plaque formation.
PS-BPR01-10: PHEOCHROMOCYTOMA MASQUERADING AS A LONG-TERM SEVERE ANXIETY DISORDER WITH PANIC ATTACKS REFRACTORY TO PSYCHIATRIC TREATMENT
Authors: Santana-Ojeda Borja , Hernandez-Lazaro Alba , de Leon-Durango Ricardo , Rios-Gomez Carlos , Perez-Rivero Jennifer Maria , Kuzior Agnieszka , Gonzalez-Diaz Paula , Arnas-Leon Claudia , Acosta-Calero Carmen , Martinez-Martin Francisco Javier 
Published: January 2023

Introduction and Objective:
Pheochromocytoma is often diagnosed in the workup of a patient with severe, refractory hypertension, but nowadays many silent pheochromocytomas are diagnosed in the workup of an incidental adrenal mass. Anxiety is also a common symptom in patients with pheochromocytoma and occasionally may be the only clinical manifestation. Hereby we describe the case of a patient with a severe refractory anxiety disorder as a bizarre presentation of pheochromocytoma.

Design and Methods:
Review of the patient's records and of the relevant literature.

Results (Case Description):
A 67-year old woman was referred to our Endocrinology Clinic for the workup of an incidental left adrenal mass found in an abdominal CT ordered in the nephrolithiasis workup after a renal colic. The patient had no previous relevant history of somatic disease. She had been suffering from anxiety disorder since she was 50, beginning with climacteric symptoms (hot flashes, irritability and mood swings) followed by severe anxiety, frequent panic attacks, insomnia and inability to concentrate. Hormonal replacement therapy had been ineffective. In the following 17 years she had consulted many public and private psychiatrists and had been treated with combinations of anxiolytic and antidepressant drugs including lormetazepam, clonazepam, bromazepam, vortioxetine, quetiapine, venlafaxine, agomelatine, risperidone, mirtazapine, but the patient's anxiety symptoms kept deteriorating. BP up to 180/110 mmHg and tachycardia up to 130 bpm had been recorded during anxiety crises but ABPM ruled out sustained hypertension or tachycardia. After the finding of the adrenal lesion the diagnostic process was straightforward. It was a solid, heterogeneous mass of about 6 cm diameter, with necrotic areas and mean densitometry of 86 UH. The lab workup showed normal creatinine and potassium, suppressed cortisol after 1 mg dexamethasone, normal ACTH, aldosterone, renin and aldosterone/renin ratio, but plasma metanephrines were above 5x the upper normal limit (634/2423 pg/mL). A MIBG scan confirmed intense uptake in the left adrenal area without abnormal extra-adrenal deposits. After standard preparation, the tumor was laparoscopically removed without complications. 1 month after the surgery plasma metanephrines were normal and the anxiety symptoms had vanished almost totally, but the patient kept taking a low dose of risperidone (1.5 mg/day) as a maintenance therapy; BP and HR remained normal

Conclusions:
Pheochromocytoma/paraganglioma should be included in the workup of patients with severe anxiety disorder, especially when refractory to treatment.
PS-B03-3: THE CD153-CPG VACCINE IS A NOVEL SENOTHERAPEUTIC OPTION TO REMOVE SENESCENCE-ASSOCIATED T CELLS
Authors: Yoshida Shota , Nakagami Hironori , Rakugi Hiromi 
Published: January 2023

Cellular senescence in primary culture cells has allowed us to understand basic individual tissue aging and cancer inhibition from the view of cellular aging. Senescent cells accumulate gradually and systemically with age, and secrete various inflammatory cytokines or chemokines, which is different from the cell fate in apoptosis. These phenomena describe the so-called senescence-associated secretory phenotype, and chronic inflammation and carcinogenesis are induced in the surrounding tissues through senescence-associated secretory phenotype factors. The senescence-associated T cells do not proliferate in response to T-cell receptor stimulation, and produce abundant inflammatory cytokines including osteopontin. Senescence-associated T cells are also increased in adipose tissue under a high-fat diet, which might be related to the progress of obesity or diabetes.
We evaluated the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice. We administered a CD153 peptide-KLH (keyhole limpet hemocyanin) vaccine with CpG oligodeoxynucleotide (ODN) 1585 (CD153-CpG) and confirmed an increase in anti-CD153 antibody levels that was sustained for several months. After being fed a HFD for 10–11 weeks, adipose senescent T cell accumulation was significantly reduced in the VAT of CD153-CpG-vaccinated mice, accompanied by glucose tolerance and insulin resistance. A histological analysis also indicated that the accumulation of macrophages and senescence-associated T cells in adipose tissues successfully reduced in the CD153-CpG-vaccinated mice.
The CD153-CpG vaccine is an optional tool for senolytic therapy. We further modify the vaccine to remove the target cells now.
PS-B05-11: IMPAIRED CELL INTERACTIONS AT THE PRE-ECLAMPTIC MATERNAL-FOETAL INTERFACE
Authors: Nonn Olivia , Debnath Olivia , Valdes Daniela , Sallinger Katja , Secener Ali Kerim , Haider Sandra , Tiesmeyer Sebastian , Coscia Fabian , Heliebi Amin El , Tilaganathan Basky , Mueller Dominik N , Huppertz Berthold , Gauster Martin , Ishaque Naveed , Herse Florian 
Published: January 2023

Hypertensive disorders in pregnancy, of which the multisystem syndrome pre-eclampsia is most severe, leading to preterm delivery, maternal mortality and life-long complications1. Pre-eclampsia lacks early screening tools2,3 and causal therapies4,5. To elucidate early disease dynamics, we present the first spatio-temporal study comparing single-nuclei transcriptomes of human preterm pre-eclamptic placentae and healthy controls, contextualising this in a comprehensive study including early and late gestational placentae and implementing spatial multi-omics methods.
Here we show trophoblast pre-fusion cells and their developmental trajectory running towards a novel trophoblast cell-state we identify as juvenile syncytiotrophoblast. We found that disturbed trophoblast development, reconstructed by spatial multi-omics and including early dysregulation in differentiation-driving transcription factor p300, likely initiates pre-eclampsia. We suggest pre-eclampsia to be a disease of dysregulated syncytiotrophoblast differentiation: Disease-specific premature differentiation of the maternal-foetal barrier leads to a senescent syncytiotrophoblastic interaction through maternal circulation with maternal vessels. This initiates a disrupted decidual maternal response via LEP, GDF15 and INHBA.
Our results highlight a disturbed cellular communication from foetal to maternal side during the development of pre-eclampsia starting with a disturbed trophoblast maturation. We provide new targets for potential early disease prevention in order to protect mother and child from increased gestational mortality and morbidity but also from life-long increased cardiovascular disease risk.
PS-B06-8: EXPLORING THE ROLE OF NECROPTOSIS IN HYPERTENSION
Authors: ODonnell Joanne A , Dinakis Evany , Jones Dakota Rhys , Muralitharan Rikeish M , Marques Francine Z 
Published: January 2023

Objective:
Altered immune cell activation plays a key role in promoting hypertension. A major question remains as to the immune system becomes activated during hypertension. A possibility is necroptosis, which a newly described form of cell death alerts the immune system to dying cells, causing inflammation. Using mice genetically unable to undergo necroptosis, we aimed to determine whether necroptosis contributes to inflammation and fibrosis or alters blood pressure during hypertension. To determine whether factors present during hypertension impact necroptosis, we examined whether Angiotensin II sensitizes human and murine cells to necroptosis.

Design and Methods:
Monocytes were sorted from peripheral blood mononuclear cells from 3 normotensive and 3 untreated hypertensive participants diagnosed with 24-h blood pressure (BP) monitoring. Necroptosis was induced in human monocytes using hTNFα (10ug/ml), SMAC mimetic (500 nM), zVAD (20uM), and in primary neonatal murine cardiomyocytes and fibroblasts from 3 litters of C57BL/6J mice using mTNFα (10ug/ml), SMAC mimetic (100 nM), zVAD (10uM), in the presence or absence of angiotensin II (Ang-II, 5 ug/ml). Viability of human cells was measured using propidium iodide by flow cytometry, and in murine cells using CellTitre-Glo Luminescent Cell Viability Assay. Hypertension was induced in male Mlkl-/- mice, which cannot undergo necroptosis, and wild-type (WT) littermate controls by implanting minipumps containing Ang-II (0.5 mg/kg/day for 28 days; n = 6/genotype). Blood pressure (BP) was measured weekly by tail-cuff.

Results:
Monocytes from hypertensive participants were not more susceptible to necroptosis than normotensive participants (% viability ± SD; 48% ± 0.11 vs 51% ± 0.04, P = 0.79). This was not altered by Ang-II treatment in normotensive (51% ± 0.04 vs 56% ± 0.11 with Ang-II, P = 0.98) or hypertensive participants (48% ± 0.11 vs 56% ± 0.18 with Ang-II, P = 0.92). Moreover, Ang-II did not alter the viability of primary murine cardiomyocytes in vitro (42% ± 23 vs 40.1 ± 17.8 with Ang-II, P = 0.79). Primary mouse cardiac fibroblasts were unable to undergo necroptosis. In vivo, there was no difference in BP of Ang-II-treated Mlkl-/- and WT control mice at 4 weeks (P = 0.87).

Conclusions:
Our findings showed that, compared to normotensive participants, monocytes from hypertensive participants were not more susceptible to necroptosis. Furthermore, Ang-II did not directly act on the necroptosis pathway in both mouse cardiac fibroblasts or human monocytes. Changes in BP were not observed between WT and MLKL knockout mice upon Ang-II treatment, suggesting necroptosis does not impact BP regulation. Further analyses are being performed to determine whether inflammation or tissue fibrosis are altered in the absence of necroptosis.
PS-B06-9: SINGLE-CELL TRANSCRIPTOMIC PROFILING OF AORTIC B CELLS DURING EXPERIMENTAL HYPERTENSION
Authors: Galvao Hericka Bruna Figueiredo , Jelinic Maria , Dona Malathi S I , Farrugia Gabriella E , Hughes Tayla G , Diep Henry , Pinto Alexander , Drummond Grant R , Vinh Antony 
Published: January 2023

Objective:
Inflammation and immunity are known to strongly influence aortic fibrosis leading to stiffening and remodelling. We have shown that genetic and pharmacological ablation of B cells affords protection from the development of aortic stiffening and remodelling associated with hypertension. Whether this protective phenotype is due to systemic effects such as reduced antibody secretion, or local B cell effector functions within the aorta remains unclear. Using single-cell transcriptomics, this study aimed to characterise the B cell populations present in the mouse aorta and identify phenotypes/effector functions which may drive inflammation and aortic remodelling.

Design and Methods:
Hypertension was induced in 12-week-old C57BL6/J mice by infusion of angiotensin II (0.7 mg/kg/day; s.c.) for 28-days via osmotic minipumps. Normotensive mice received vehicle infusion (0.5% NaCl, 0.1% acetic acid). Weekly systolic blood pressure (SBP) measurements were acquired by tail-cuff plethysmography. High-resolution ultrasound imaging was used for pulse wave velocity (PWV) measurements on day 28. Thoracic and abdominal aortas were then isolated and digested for single-cell transcriptomic analyses. Aortic suspensions were stained with Calcein Blue and Vybrant Ruby to sort for metabolically active, nucleated cells. RNA libraries were generated using the 10x Chromium platform.

Results and Conclusions:
Angiotensin II caused significant increases in SBPs (∼180 mmHg) compared to vehicle treated mice (∼120 mmHg). Hypertensive (HT) mice had increased aortic PWV (∼4 m/s) compared to normotensive (NT) mice (∼1 m/s). Single-cell transcriptomic analyses revealed a near 2-fold increase in B cells present in the aorta of hypertensive mice. Leiden-based community detection identified 7 clusters within the aortic B cell population, including pro-B cells, pre-BCR-independent B cells, transitional B cell populations, B1 and B2 B cells, as well as antibody secreting cells. A greater number of B2 B cells was observed in the hypertensive aorta (58% HT vs 36% NT), without an observable increase in B1 B cell numbers. Gene ontology (GO) analysis of aortic B2 B cells from angiotensin II-treated mice revealed an upregulation in biological processes associated with B cell proliferation (GO:0042100), B cell activation (GO:0042113) and leukocyte differentiation (GO:0002521) compared to vehicle controls. Interestingly, the majority of antibody secreting cells in the aorta appear to be derived from B1 B cells in both vehicle (∼82%) and angiotensin II-treated mice (∼96%). In summary, hypertension is associated with a divergent aortic B cell transcriptome reflective of an augmented immune response, with observable shifts in composition which may be associated with inflammation and aortic remodelling.
PS-B08-4: CHRONIC INTERMITTENT HYPOXIA INDUCES RENAL FIBROSIS BY MR ACTIVATION
Authors: Zhang Cui juan , Yang Fan , Chang Yi , Xiong Yun zhao , Shimosawa Tatsuo , Xu Qing you 
Published: January 2023

Purpose:
Obstructive sleep apnea is mainly characterized by chronic intermittent hypoxia (CIH), which is associated with chronic kidney disease. Macrophage is known to play an important role in renal fibrosis. However, little is known of the potential role of macrophage-to-myofibroblast transition (MMT) in hypoxic conditions. The aim of this study was to understand how infiltrating macrophages may contribute to renal fibrosis in hypoxic conditions.

Methods:
In this study, 30 adult male sprague dawley (SD) rats were randomly divided into normoxic control(NC), chronic intermittent hypoxia(CIH), and eplerenone(EPL) groups-each containing ten rats. The CIH and EPL groups were exposed to hypoxia in a commercial hypoxic chamber for 5 weeks. Rats in the EPL group were administered EPL orally via diet for 5 weeks. All rats were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, western blot, immunohistochemistry. The RAW264.7 macrophages were subjected to 24 hours of hypoxia and 12 hours of reoxygenation. Cells were collected for immunofluorescence staining.

Results:
In addition to blood pressure, renal aldosterone level was also increased in CIH rats. Massons trichrome and Sirius red staining showed significantly higher collagen deposition and fibrosis in CIH rats. A markedly increased co-expression of α-SMA and CD68 in vitro and in vivo after CIH exposure. MR nuclear translocation was seen in hypoxic macrophages. Western blot showed that the expression of SGK-1 and p-SGK-1 was upregulated. These effects were reversed by MR blocker (EPL).

Conclusions:
CIH-induced macrophage infiltration, an important source of myofibroblasts, might participate in the development of renal interstitial fibrosis. These effects were reversed by EPL. Therefore, we speculate MR activation may be related to CIH-induced renal fibrosis.
PS-B08-6: ROLE OF THE HMGB-1/RAGE AXIS AND MINERALOCORTICOID RECEPTOR IN THE PATHOGENESIS OF ACUTE KIDNEY INJURY
Authors: Otsuka Tomoyuki , Ueda Seiji , Nagasawa Hajime , Okuma Teruyuki , Nakata Masami , Sato Koji , Kobayashi Takashi , Murakoshi Maki , Gohda Tomohito , Matsui Takanori , Yamagishi Shoichi , Suzuki Yusuke 
Published: January 2023

Background:
Endothelial dysfunction plays a central role in the pathogenesis of cardio-renal syndrome. High mobility group box-1 (HMGB-1) is a protein with various roles in different cellular compartments, and indirectly regulates the activity of transcription and DNA repair in the nucleus. On the other hand, during tissue damage, it is released into the extracellular environment as damage-associated molecular patterns (DAMPs). HMGB-1 is elevated in the pathogenesis of acute kidney injury (AKI) and be involved in endothelial dysfunction through binding to toll like receptor (TLR) and receptor for advanced glycation end products (RAGE). In addition, we recently demonstrated that RAGE-mediated Rac1 activated mineralocorticoid receptor (MR) and subsequently resulted in podocytes damage. In the present study, we hypothesized that crosstalk between HMGB-1/ RAGE and Rac1-MR pathways could contribute to endothelial dysfunction in AKI.

Methods:
In the present study, we performed a renal ischemia-reperfusion model (I/R group) on C57BL/6J mice to evaluate the expression of Rac1-MR pathway and organ damage. In addition, the I/R group was pretreated with MR blocker (esaxerenone) and evaluated in the same way. In vitro study, we investigated whether HMGB-1 could activate Rac1-MR axis and thus induce endothelial injury in cultured human umbilical vein endothelial cells (HUVECs) by assessing expression levels of genes for MCP-1 and NF-κB with or without administration of RAGE aptamer or MR blocker.

Results:
In the I/R group, MR activation assessed by translocation into the nucleus and enhanced RAGE expression were observed along with HMGB-1 and RAGE elevation, and pretreatment with MR blocker suppressed the elevation of serum creatinine levels as well as tubular necrosis. Further, the loss of peritubular capillaries observed in I/R kidney was markedly suppressed by MR blocker. In vitro study, HMGB-1 supplementation significantly increased RAGE expression, GTP-bound Rac1 and enhanced MR translocation into the nucleus in HUVECs as well. We also found that HMGB-1 upregulated MCP-1 and NF-κB, all of which were significantly blocked by pretreatment of RAGE aptamer and MR blocker.

Conclusion:
These results suggest that there may be a close relationship between HMGB-1/ RAGE axis and Rac1/ MR activation, thus contributing endothelial injury. Using RAGE aptamer or MR blocker could be novel therapeutic strategies against endothelial dysfunction in patients with AKI.