bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR23-01 The Nonredundant Role Of Beta-Amyloid In Mediating Tonic PTH Secretion In Physiological And Pathological States
Authors: Tu Chia-Ling , Cheng Zhiqiang , Alejandra Pena Karina , Szeto Nicholas , Ann Sosa Julie , Vilardaga Jean-Pierre , Koh James , Chang Wenhan 
Published: October 2023

Abstract
Disclosure: C. Tu: None. Z. Cheng: None. K.A. Pena: None. N. Szeto: None. J.A. Sosa: None. J. Vilardaga: None. J. Koh: None. W. Chang: None.
Understanding the mechanisms driving parathyroid hormone (PTH) hypersecretion in primary hyperparathyroidism (PHPT) is essential for better management of this common endocrinopathy. Prior studies showed that reduced Ca2+-sensing receptor (CaSR) expression and the subsequent increases in heterodimerization of the CaSR with the type B γ-aminobutyric acid receptor 1 (GABAB1R) are causally linked to PTH hypersecretion in PHPT mouse models (Nat Metab 2:243-255). We further showed that expression of the putative GABAB1R ligands, amyloid precursor protein (APP) and its proteolytic product, β-amyloid (Aβ1-42), is significantly upregulated in adenomas of PHPT patients associated with vitamin D insufficiency/deficiency when compared to normal donor controls. The current study aims to delineate the actions of Aβ1-42 in promoting tonic PTH secretion and its interactions with vitamin D receptor (VDR) signaling in parathyroid glands (PTGs) in basal and PHPT states. We show that Aβ1-42 (200 nM) stimulated tonic PTH secretion in cultures of normal human PTGs without shifting the calcium/PTH secretion setpoint (Ca2+-setpoint). In contrast, conditional knockout (KO) of the App gene in the parathyroid cell (PTC) of PTCAppΔflox/Δflox mice significantly reduced serum PTH levels (KO: 64±13 pg/ml vs Control: 109±12 pg/ml; p&lt;0.05, n=8) despite hypocalcemia, indicating hypoparathyroidism. In PTGs cultured from the PTCAppΔflox/Δflox mice, supplementation of Aβ1-42 dose-dependently (EC50=5.6 nM, p&lt;0.001) increased PTH secretion without altering the Ca2+-setpoint. However, the stimulatory effects of Aβ1-42 on tonic PTH secretion were completely abrogated in the PTGs with concurrent deletions of App, Casr and Gabbr1 genes, supporting a direct action of Aβ1-42 on CaSR and/or GABAB1R. The latter notion is further supported by the ability of Aβ1-42 to stimulate cAMP production in cells co-expressing CaSR and GABAB1R. PTC-specific deletion of the Vdr gene in the PTCVdrΔflox/Δflox mice led to elevated serum PTH levels in vivo and increased tonic PTH secretion with unaffected Ca2+-setpoint in PTGs in vitro. Concurrent ablation of the App gene completely normalized serum PTH levels in the PTCVdrΔflox/Δflox mice and prevented PTH hypersecretion in their PTGs in culture. These findings support a critical role of the APP-derived Aβ1-42 in mediating tonic PTH secretion in the normal physiological state and suggest a new mechanism driving PTH hypersecretion in PHPT due to vitamin D deficiency.
Presentation: Saturday, June 17, 2023
THU583 Cardioprotection By Nitric Oxide Is Mediated Via Mitochondrial Function In Rodents
Authors: Islam Kazi , Islam Rahib , Draper Alexis 
Published: October 2023

Abstract
Disclosure: K. Islam: None. R. Islam: None. A. Draper: None.
Background: Reduced nitric oxide (NO)bioavailability and decreased expression of mitochondrial transcription factor A (TFAM) occurs in the setting of heart failure (HF). TFAM promotes transcription of mitochondrial DNA, mitochondrial biogenesis, respiratory chain activity, and ATP synthesis. We investigated the effects of oral NaNO2therapy to increase NO in chronic HF following acute myocardial infarction and examined the effects of NaNO2 on the activation of TFAM, mitophagy, and antioxidant signaling pathways. Methods: Male C57/BL6J mice underwent 60 minutes of myocardial ischemia (MI) induced by left coronary artery (LCA) occlusion followed by 4 weeks of reperfusion. NaNO2 or saline vehicle (VEH)was administered at a dose of 165 µg/kg at reperfusion and then daily for 4weeks in the drinking water (100 mg/L). Left ventricular ejection fraction (LVEF) was determined at baseline and at 4 weeks of reperfusion. At 4 weeks of reperfusion myocardial tissue samples were collected and analyzed by RT-qPCR, immunoblot, oxidative stress assay, and protein sulfhydration assay. Results: NaNO2 administration markedly preserved left ventricular ejection fraction (LVEF) and improved left ventricular diastolic and systolic dimensions at 4 weeks as compared to VEH. Mitochondrial antioxidant proteins, SOD2 (MnSOD), peroxiredoxin-3 (Prx-3) and thioredoxin 2 (TXN2) (p &lt; 0.05) were markedly increased in NaNO2treated mice compared to VEH. Expression of mitophagic markers, p62 (p &lt;0.05) and Map1lc3 (p &lt; 0.05) were significantly increased in NaNO2treated HF mice as compared to VEH. Expression of mitochondrial quality control such as PINK1 and PARKIN2 were also markedly increased HF mice after treated with nitrite therapy as compared with VEH. Marked induction of sulfhydration of interferon regulator factor 1 (IRF-1) as well as upregulation of mitochondrial transcription factor A (TFAM) (p &lt; 0.05) and suppression of DNA methyltransferase3a (Dnmt-3a) (p &lt; 0.05) were observed in NaNO2 treated ischemic HF mice as compared with VEH. Conclusions: Our results clearly demonstrate thatNaNO2 therapy improves left ventricular function during ischemic HF through induction of antioxidant signaling, mitophagy, sulfhydration of IRF-1and TFAM resulting in increased mitochondrial biogenesis.
Presentation: Thursday, June 15, 2023
FRI091 Treatment Of Secondary Hyperlipidemia Due To Nephrotic Syndrome
Authors: Girard Jeanette , Quadri Hamza , Jiang Bryan , Kapoor Force Bahar , Abushamat Layla , Schneider Aguirre Rebecca 
Published: October 2023

Abstract
Disclosure: J. Girard: None. H. Quadri: None. B. Jiang: None. B.K. Force: None. L. Abushamat: None. R.S. Aguirre: None.
Introduction: Secondary Hyperlipidemia associated with nephrotic syndrome contributes to significant cardiovascular morbidity. The elevated atherogenic lipoprotein levels are caused by upregulation of HMG-CoA reductase and downregulation of lipoprotein lipase. More recently, studies in mice have linked PCSK9 and Inducible Degrader of the LDL Receptor (IDOL) as primary contributors to hypercholesterolemia in nephrotic syndrome due to the decrease in LDL receptor recycling (1). Treating nephrotic syndrome is the first-line treatment for the associated secondary hyperlipidemia. Since exposure time to atherogenic lipoproteins matters in the development of cardiovascular disease, statins, with or without ezetimibe, are utilized. PCSK9 inhibitors are initiated if LDL remains elevated despite these measures. This case report highlights a severe case of hypercholesterolemia associated with nephrotic syndrome and treatment response. Clinical Case: A 55-year-old male with no significant past medical history presented to the emergency department with shortness of breath and lower extremity edema. He denied a family and personal history of premature cardiovascular disease. Initial evaluation revealed a serum total cholesterol on 10x dilution of 833.9 (&lt;/=200mg/dL), calculated LDL 718mg/dL (&lt;100mg/dL), triglycerides 381mg/dL (&lt;150mg/dL), HDL 39.3mg/dL (40-60mg/dL), Apo B &gt;400mg/dL (&lt;90mg/dL), and Lp(a) 17.5mg/dL (&lt;75mg/dL). His serum albumin was &lt;1.5g/dL (4.2-4.5g/dL), creatinine 2mg/dL (0.7-1.3mg/dL), and 24-hour calculated urinary protein level 10,294mg/24-hour (30-150mg/24-hour). A kidney biopsy revealed a mixed Type III and Type V Lupus Nephritis. The patient started lupus treatment along with atorvastatin 80mg qHS, fenofibrate 45mg daily, and ezetimibe 10mg daily. His LDL decreased to 418mg/dL (&lt;100mg/dL) after 15 days. The patient continued to have undetectable albumin although kidney function improved after 2 months. We planned to initiate PCSK9 inhibitor treatment for further LDL reduction pending treatment of lupus, but patient died from septic shock prior to initiation. Conclusion: This case illustrates that extremely elevated LDL levels from nephrotic syndrome resulted in a nearly 60% reduction of LDL with statin and ezetimibe treatment. Statins, ezetimibe and PCSK9 inhibitor therapy should be considered stepwise when treating secondary hyperlipidemia from nephrotic syndrome. 1. LIU S, VAZIRI ND. ROLE OF PCSK9 AND IDOL IN THE PATHOGENESIS OF ACQUIRED LDL RECEPTOR DEFICIENCY AND HYPERCHOLESTEROLEMIA IN NEPHROTIC SYNDROME. NEPHROL DIAL TRANSPLANT. 2014 MAR;29(3):538-43. DOI: 10.1093/NDT/GFT439. EPUB 2013 OCT 28. PMID: 24166456
Presentation: Friday, June 16, 2023
FRI106 Outcomes Of SGLT2 Inhibitors In Patients With Heart Failure With Or Without Diabetes In A Tertiary Care Center In Saudi Arabia
Authors: Alqifari Saleh F , Mohammed Adil , Anwar Eman , Niazi Kashan , Aldawish Rahaf , Mutlaq Mai , Binsaqr Maha , Khojah Asmaa , Albahli Rand , Amirthalingam Palanisamy , Aljabri Ahmed , Ziada Shimaa , Alshaye Bshaier , Almlkhlef Salman 
Published: October 2023

Abstract
Disclosure: S.F. Alqifari: None. A. Mohammed: None. E. Anwar: None. K. Niazi: None. R. Aldawish: None. M. Mutlaq: None. M. Binsaqr: None. A. Khojah: None. R. Albahli: None. P. Amirthalingam: None. A. Aljabri: None. S. Ziada: None. B. Alshaye: None. S. Almlkhlef: None.
Objectives: The role of Sodium-glucose cotransporter 2 (SGLT2) inhibitors in the reduction of renal complications, death, and hospitalization in patients with heart failure has been highlighted in recent trials. However, real-world evidence is lacking, especially in the Middle East. This study aims to examine SGLT2 inhibitors outcomes in patients with heart failure with or without diabetes mellitus. Materials and Methods: This is a retrospective single-center study conducted in Saudi Arabia that reviewed patients’ data from July 2021 to June 2022. We included adults (≥18 years) diagnosed with heart failure and treated with Empagliflozin for a minimum of 3 months. Results: A total of 45 patients were included in the study. A significant difference was detected among the group of patients with diabetes and no diabetes in baseline diastolic blood pressure (DBP), baseline left ventricular ejection fraction (LVEF), and the use of diabetic medications (p= 0.008, &lt;0.001, 0.008), respectively. SGLT2 inhibitors use signaled a trend towards improvement in HbA1C, LVEF, and ED visits frequency in both groups, however, findings were non-statically significant. Conclusions: Although the use of SGLT2 inhibitors for at least 3 months improved HbA1C, LVEF, and ED visit frequency in both groups, results were not statistically significant. These findings warrant larger studies to further evaluate the clinical outcomes of SGLT2 inhibitors in Saudi patients.
Presentation: Friday, June 16, 2023
FRI119 Cardiac Biomarkers In Fabry Disease Exhibit Distinct Associations With Cardiovascular Outcomes: A (Rare) Prism For Cardiovascular Endocrinology
Authors: Shemesh Elad , Rusk Rosemary , Feigin Paul , Deegan Patrick 
Published: October 2023

Abstract
Disclosure: E. Shemesh: None. R. Rusk: None. P. Feigin: None. P. Deegan: None.
Background: Fabry disease (FD) (OMIM 301500) is a rare x-linked metabolic disorder. Cardiovascular involvement in this rare metabolic disorder is common, including hypertrophy, fibrosis, heart failure and arrythmias. Troponin concentrations are often continuously elevated in FD patients, which at times may lead to false assumptions and unnecessary invasive investigations. Furthermore, while nt-proBNP, another cardiac biomarker, is regarded by some as a valuable biomarker in FD, its concentrations might be falsely high due to renal involvement in the disease. We sought to explore the associations between these cardiac biomarkers with myocardial architecture and clinical outcomes in patients with FD. Hypothesis: Biomarkers in FD associate similarly with myocardial architecture and clinical outcomes. Results: 107 patients from a tertiary referral center in the United Kingdom were included in this study. Mean age at first visit was 44.5±17 years. Study population was composed of 40 males and 67 females. Twenty males and 43 females carried a classic mutation. At baseline, 27% had elevated troponin concentrations and 30% of patients had elevated nt-proBNP concentrations. Throughout follow-up, 17 cardiac-related hospitalizations were recorded, and 12 cardiac-related deaths occurred. While troponin and nt-proBNP concentrations at baseline were closely related (r= 0.5, p &lt; 0.05), distinct associations with future occurrence of cardiac architecture pathologies were noted: elevated troponin concentrations associated with presence of late gadolinium enhancement and left ventricular hypertrophy in a statistically significant manner (late gadolinium enhancement: r=0.54, p&lt;0.05; hypertrophy: r-0.45, p&lt;0.05), but nt-proBNP did not. However, both biomarkers associated with adverse clinical outcomes, and nt-proBNP displayed stronger correlation with future heart failure events than troponin (r= 0.52, p&lt;0.05 vs r=0.3, p&lt;0.05). Neither troponin nor nt-proBNP baseline concentrations associated with the implantation of cardiac device (defibrillator or pacemaker). Conclusions: Cardiac biomarkers associate differently with myocardial architecture pathologies, but similarly with clinical outcomes in FD. Our results imply distinct roles for troponin and nt-proBNP in adverse cardiac events in FD.
Presentation: Friday, June 16, 2023
FRI126 Autoreactive T Cells To Angiotensin II Type 1 Receptor In Salt-dependent Hypertension Due To Primary Aldosteronism
Authors: Scarpa Riccardo , Piazza Maria , Caroccia Brasilina , Carraro Samuela , Vianello Fabrizio , Cinetto Francesco , Agostini Carlo , Seccia Teresa M , Paolo Rossi Gian 
Published: October 2023

Abstract
Disclosure: R. Scarpa: None. M. Piazza: None. B. Caroccia: None. S. Carraro: None. F. Vianello: None. F. Cinetto: None. C. Agostini: None. T.M. Seccia: None. G. Rossi: None.
Compelling evidence suggested a role of acquired immunity in hypertension and hypertension-mediated organ damage (HMOD), but the pathogenic role of this acquired immunity is still unknown. Primary Aldosteronism, the paradigm of salt-dependent hypertension, is characterised by a more prominent HMOD than primary (‘essential’) hypertension and by high titer of autoantibodies against the type 1 angiotensin receptor (AT1R). As T cells are broadly recognised as HMOD-mediators, we aim to investigate: 1) the presence of AT1R-autoreactive T cells in PA; 2) aldosterone rapid and chronic effect on AT1R-autoreactive T lymphocytes; 3) the presence and functional role of know aldosterone receptors on T lymphocytes. The presence of AT1R-autoreactive T cells in 11 PA patients was investigated by flow cytometry after stimulation with pool of peptides spanning the full length of AT1R. The expression of mineralocorticoid receptor (MR) and G Protein-Coupled Estrogen Receptor (GPER) on T cells was tested by measuring mRNA copy number by droplet digital PCR and immunoblotting from healthy donors (HD) subjects and PA patients. Peripheral blood mononuclear cells (PBMCs) from PA patients were exposed to aldosterone 10-10 M with or without MR antagonist (canrenone) and GPER agonist (G1) and antagonist (G36). We evaluated the effect of aldosterone on CD8+ T cells by measuring IFNɣ release with flow cytometry. PA patients were found to have CD8+ AT1R-autoreactive T cells after activation of PBMC with AT1R peptides. MR and GPER were detected both at mRNA and protein level in CD4+ and CD8+ T cells with the following rank of expression GR&gt;MR&gt;&gt;GPER. Aldosterone significantly increased IFNɣ release in CD8+ T-cell both under chronic and acute stimulation. Chronic exposure to aldosterone increased IFN-γ production by CD8+ T cells by acting via the MR, as it was prevented (p &lt; 0.004) by canrenone, while the rapid aldosterone action was MR and GPER mediated, as it was reduced by canrenone (p &lt; 0.003), but also by G36 (p &lt; 0.02), and mimicked by G1. These results showed the presence of AT1R-autoreactive T cells in patients with PA. Moreover, upon of MR and GPER receptor stimulation with aldosterone, AT1-R specific CD8+ T cells undergo profound changes that mediated a strong cytotoxic response towards AT1-R-expressing organs.
Presentation: Friday, June 16, 2023
FRI134 Transcriptomic Profiling Of Monocytes To Seek A Potential Biomarker For Primary Aldosteronism
Authors: Libianto Renata , Karthigan Nikshay , Morgan James , Powell David , Fuller Peter J , Jennifer Young Morag , Yang Jun 
Published: October 2023

Abstract
Disclosure: R. Libianto: None. N. Karthigan: None. J. Morgan: None. D. Powell: None. P.J. Fuller: None. M.J. Young: None. J. Yang: None.
Primary aldosteronism (PA), the most common endocrine cause of hypertension, is associated with increased cardiovascular risk compared with essential hypertension. The diagnosis of PA currently relies on measurements of plasma aldosterone and renin levels which can be compromised by patient- or assay-related issues and relies on arbitrary thresholds. A cellular marker that reflects excess endogenous aldosterone activity could enhance the diagnostic process. Mineralocorticoid receptor (MR) activation in macrophages has previously been shown to play a key role in mediating cardiovascular injury. Macrophage precursors, the monocytes, also express MR and can be easily isolated from circulation. We therefore sought to identify unique transcriptomic markers of aldosterone excess in peripheral blood monocytes. Monocytes were isolated from nine male patients with unilateral PA before and 3 months after curative adrenalectomy. Each patient’s post-adrenalectomy samples served as the control for comparison with the pre-adrenalectomy samples. RNA sequencing (RNA-seq) was performed on monocyte RNA samples to identify differentially expressed genes (DEGs), followed by evaluation using a second method by real-time quantitative PCR (RT-qPCR). Distinct clustering of gene expression was observed between the “before” and “after-surgery” samples with 1679 significantly differentially expressed (false discovery rate &lt;0.05). The top 26 DEGs were selected for evaluation by RT-qPCR. Differences were observed in the relative expression of phosphoglycerate mutase 1 (PGAM1), ferrochelatase (FECH), and nuclear enriched abundant transcript 1 (NEAT1) genes pre- and post-surgery. The ratios of the relative expression of these genes accentuated the difference between the before- and after-surgery samples. In conclusion, differential gene expression was found between monocytes of patients with unilateral PA before and after adrenalectomy. Further validation studies are needed in female patients and those with bilateral PA and essential hypertension. These transcriptomic markers or their ratios have the potential to serve as novel biomarkers of aldosterone excess.
Presentation: Friday, June 16, 2023
FRI136 Adrenal Venous Sampling Criteria For Chemiluminescent Enzyme Immunoassay
Authors: Nakai Kazuki , Tsurutani Yuya , Irie Koki , Teruyama Kyoko , Saito Jun , Omura Masao , Nishikawa Tetsuo 
Published: October 2023

Abstract
Disclosure: K. Nakai: None. Y. Tsurutani: None. K. Irie: None. K. Teruyama: Employee; Self; Fujirebio Inc. J. Saito: None. M. Omura: None. T. Nishikawa: None.
Objective: In primary aldosteronism (PA), plasma aldosterone concentration (PAC) was measured by radioimmunoassay (RIA), but the supply of the RIA kit was discontinued in March 2021 in Japan. The Japan Endocrine Society's 2021 Clinical Practice Guideline for the Diagnosis and Management of PA recommends that PAC measured by chemiluminescent enzyme immunoassay (CLEIA), which yields standardized LC-MS/MS compliant measurements, be used for clinical judgment. Because CLEIA shows a lower PAC than RIA, various cutoff values for PA need to be revised. Although conversion formulas for RIA and CLEIA for various kits have been provided, these conversions were studied mainly using samples representing aldosterone concentrations in peripheral blood; thus, it is unclear whether the same conversion formula can be used for samples obtained by adrenal venous sampling (AVS). In this study, we examined PAC conversion in AVS samples and the criteria for AVS when measured using CLEIA. Methods: PAC of 415 adrenal venous blood samples from AVS (including segmental AVS) from 63 patients with PA, were measured using RIA and CLEIA methods. The established conversion formula for PAC in peripheral blood samples was PAC (CLEIA) = 0.852 × PAC (RIA) − 36.0. PAC and aldosterone/cortisol ratio (A/C ratio) conversion formulas were determined between the two assays for AVS samples. Moreover, the CLEIA conversion value, which corresponds to the AVS criteria of conventional RIA, was obtained. Results: The median [interquartile range] PAC (CLEIA) in the samples was 9823.3 [3659.8-20600.5]. PAC measured using CLEIA was significantly correlated with RIA, and the correlation coefficient was 0.971. The PAC conversion formula determined was PAC (CLEIA) = PAC (RIA) × 0.7723 - 1199 pg/mL. PAC at 14,000 pg/mL in RIA was equivalent to 9,613 pg/mL in CLEIA. The correlation coefficient for the A/C ratio was 0.997, and the conversion formula was A/C (CLEIA) = A/C (RIA) × 0.7864 - 2.427. Discussion: Samples obtained from AVS had a much higher level of PAC than those obtained from peripheral blood. The PAC conversion formula for samples in AVS has a very large intercept compared with those in peripheral blood. Thus, the results of AVS tested by CLEIA should be interpreted with care because of the differences in the conversion formula. A different cut-off value may also be needed when evaluating the lateralization ratio because of the large intercept. Conclusion: PAC conversion formulas for AVS samples using CLEIA and RIA methods were obtained. The study outcomes are useful for interpreting AVS results using the CLEIA.
Presentation: Friday, June 16, 2023
FRI150 Individualized And Shorter Follow-up With Immunohistochemical Staining In Unilateral Primary Aldosteronism?
Authors: Gunnarsdottir Hrafnhildur , Agnarsson Bjarni A , Jonasdottir Sigurrós , Gudmundsson Jón , Birgisson Guðjón , Sigurjónsdóttir Helga Á 
Published: October 2023

Abstract
Disclosure: H. Gunnarsdottir: None. B.A. Agnarsson: None. S. Jonasdottir: None. J. Gudmundsson: None. G. Birgisson: None. H.Á. Sigurjónsdóttir: None.
Indroduction: Clinical significance of specific antibody staining (SAS) for unilateral primary aldosteronism (PA) has been unclear. Individualized follow-up of PA patients could be in sight. Long-term outcome of patients, classified based on immunohistochemical staining, needs further investigation. Aims: We aimed to assess long-term clinical outcome (using PASO criteria) for unilateral PA, classifying patients based on SAS. Methods: The study was a nationwide observational study, with up to 11 years follow-up, executed in 2007-2016 at Landspitali National University Hospital of Iceland, tertiary referral center. Patients were diagnosed and treated in line with the current guidelines. All unilateral PA patients, ( n=26) age 28-73 years, who underwent adrenalectomy in Iceland during the study period were included. H&E stained tissue slides were stained using specific CYP11B1 and -B2 antibodies. All cases were re-evaluated and classified as adenoma (APA) or non-adenoma (adrenal hyperplasia, unilateral adrenal micronodules (UMN) or aldosterone producing cell clusters (APCC)). Data collection consisted of aldosterone, renin and cortisol values, antihypertensive drug count, potassium supplementation, blood pressure and serum potassium pre-intervention and throughout follow-up and histopathology results post-adrenalectomy. Results: Following SAS, APA was seen in 21 adrenals, APCC in three and UMN in two. Immunohistochemical staining altered histopathological diagnosis in 27% of the patients. Around 80% of each subgroup had partial clinical success. No APA patient with complete clinical success at 12 months (n=4) relapsed during follow-up. Conclusions: We found SAS mandatory for accurate histopathological diagnosis of PA. Our results indicate that a subgroup of APA patients can be discharged safely early.
Presentation: Friday, June 16, 2023