bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-R01-9: THE PERILS OF GRAPEFRUIT: A POTENTIALLY LETHAL INTERACTION WITH VERAPAMIL
Authors: de Leon-Durango Ricardo , Hernandez-Lazaro Alba , Rios-Gomez Carlos , Santana-Ojeda Borja , Kuzior Agnieszka , Perez-Rivero Jennifer Maria , Arnas-Leon Claudia , Acosta-Calero Carmen , Gonzalez-Diaz Paula , Tocino-Hernandez Alba Lucía , Martin-Perez Marta , Martinez-Martin Francisco Javier 
Published: January 2023

Objective:
Hereby we describe a case of severe toxicity induced by a standard dose of slow-release verapamil

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

Results (Case Description):
A 57-year old woman had been diagnosed with hypertension by her family physician, but her management had been complicated with intolerance to multiple antihypertensive drugs. On the occasion of a family conflict, she developed a hypertensive crisis, with a holocranial headache, tremor and palpitations, but no symptoms of ischemia on the EKG. After discharge from the Emergency Room she was referred to our Outpatient Hypertension Clinic in order to rule out secondary hypertension. For the workup, and in order to avoid interference with the renin-angiotensin-aldosterone system she was switched to slow-release verapamil 120 mg twice a day. One month afterwards the workup was completed: primary aldosteronism, pheochromocytoma/paraganglioma, renovascular hypertension and Cushing's syndrome had been ruled out. Her BP was adequately controlled with verapamil, with ABPM confirmation, and her tolerance was good. Considering her multiple drug intolerances, we decided to keep her on verapamil. Four months afterwards, the patient was brought back to the Emergency Room with severe hypotension and bradycardia, extreme asthenia, generalized rubor and diaphoresis, with normal lab tests except for mild creatinine elevation in the context of dehydration. Her SBP was 74 mmHg, with DBP not measurable, and HR 39 lpm; the EKG showed Wenckebach 2:1 AV block. After 48 hr in the Emergency Room with saline infusion and basic support measures the patient was discharged and referred again to our Clinic for reevaluation. A verapamil overdose was suspected, but the patient was adamant that she had always taken verapamil exactly as prescribed. A detailed anamnesis revealed that the patient had put on some weight the previous month and decided to lose it with a novelty diet based on the intake of about 2 liters of grapefruit fruit daily plus protein. She was switched to indapamide 2.5 mg daily with good tolerance and adequate BP control.

Conclusions:
Grapefruit juice contains 6’-7’dihydrohybergamottin, a powerful inhibitor of the key drug metabolizing enzyme CYP3A4, potentially causing accumulation of many common drugs such as verapamil, statins, ticagrelor, sildenafil, amiodarone or cisapride, and related toxicity. We need to remember that prescription drugs do not only interact among themselves but also with herbal remedies and common foodstuffs such as grapefruit.
PS-R02-10: SYNCOPE ASSOCIATED WITH PAROXYSMAL ATRIAL FIBRILLATION AND ITS TREATMENT WITH CRYOABLATION
Authors: Ulusan Sebahat , Kuyumcu Mevlut Serdar 
Published: January 2023

Aims:
The main objective to present this case is creating awareness about syncope attacks and cryoablation procedure.

Case report:
A 60-year-old female patient was admitted to the cardiology department of Suleyman Demirel University Research and Education Hospital from an external center with the complaint of syncope attacks. The patient stated that she fainted with loss of consciousness while working. Patient was diagnosed before with hypertension and is being under treatment with 5 mg of ramipril (1x1). Patient was examined with echocardiography and electrocardiogram, after evaluating results, pathology was not founded. Ejection fraction (EF) %60, mitral regurgitation and tricuspid regurgitation were minimum, pulmonary artery pressure was 28 mmHg. For further examination, rhythm Holter and tension Holter were preferred. As results of tension holter, tension was regular and there was no hypotension. As results of rhythm holter, multiple paroxysmal atrial fibrillation attacks with the longest 5.3 pause was observed. Average heart rate was 55 beats per minute, for this reason beta blockers werent chosen as a treatment. Patient was recommend to undergo cryoablation procedure. Cryoablation procedure was performed with Medtronic The Arctic Front Advance through femoral vein. Afterwards, a transeptal passage was made from the right atrium to the left atrium with a Brockenbrough needle. Four pulmonary veins in order of left lower, left upper, right lower, right upper were isolated from extra focuses electrophysiologically without complication. The patient was called for monthly checkups and prescribed with edoksaban tosilat. After checkups, syncope attacks and palpitations were not founded. In three month checkup, the patient was examined with rhythm Holter, pause and paroxysmal atrial fibrillation were not observed.

Results:
Syncope is a sudden consciousness with a loss of postural tone which caused by pathologies. Epidemiology and prognosis of syncope is various in general population. Syncope can be caused by neurological diseases or cardiovascular problems. Since syncope attacks occur as a symptom of many diseases, they ought to be investigated gradually. Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope. However, in our case, there were pauses due to atrial fibrillation with a slow ventricular response, and syncope probably developed due to this phenomenon. Therefore, ablation was a curative treatment in our patient. As a conclusion further studies are needed to figure out the relationship between syncope and cardivascular diseases.
PS-R02-11: CORONARY ARTERY ANEURYSM IN ADULT: KAWASAKI DISEASE?
Authors: Ulusan Sebahat , Kuyumcu Mevlut Serdar 
Published: January 2023

Aims:
The main objective to present this case is creating awareness about Kawasaki Disease and the post- disease conditions such as aneurysm.

Case report:
A 62-year-old male patient was admitted to the cardiology department of Suleyman Demirel University Research and Education Hospital with the complaint of stable angina pectoris (Class 2, New York Heart Association Functional Classification). Patient was diagnosed before with diabetes mellitus, hyperlipidemia, atopic dermatitis, xerosis cutis and paroxysmal atrial fibrillation. Pateint was examined with effort test and after results of the effort test, patient was recommended to undergo coronary angiography to check up conditions of the coronary arteries. Coronary angiography of the selective left radial artery was performed with JL 3.5 and JR 4 catheters. Diffuse ectasia, coronary slow flow was observed in the coronary arteries. After looking and evaluating the coronary angiography results, patient was questioned about Kawasaki Disease. When we peruse the history of the patient, high fever disease was detected. This condition of the coronary arteries was explained and maximal medical treatment with beta blocker, ranolazine, statin and edoksaban tosilat was prescripted.

Results:
Kawasaki disease is an acute vasculitis disease that mostly affects infants and children. Coronary artery aneurysms occur in the majority of cases. Pediatricians and cardiologists should keep in their mind that this condition is significant and ought to be recognized. Further studies are needed to detect children with Kawasaki disease.
PS-BPB01-3: ANGIOTENSIN (1–7)-MEDIATED PREVENTIVE EFFECT OF ANGIOTENSIN II TYPE 1 RECEPTOR ANTAGONISTS ON ABDOMINAL AORTIC ANEURYSM PROGRESSION IN OPG-KO MICE
Authors: Karasaki Kohei , Kokubo Hiroki , Ishida Mari , Sakai Chiemi , Yoshizumi Masao 
Published: January 2023

Objective:
Hypertension is one of the major risk factors for onset of abdominal aortic aneurysm (AAA), which is a local enlargement of the abdominal aorta. Therefore, anti-hypertensive drugs, including angiotensin (Ang) II type 1 receptor blocker (ARB), have been expected to limit AAA growth. However, the efficacy of ARB against AAA in clinical settings is controversial. In the present study, we attempted to elucidate a mechanism by which ARB inhibits AAA progression.

Design and method:
To examine the effect of ARB against AAA progression, olmesartan (20 mg/kg/day) was administered orally to male wild-type mice and osteoprotegerin (Opg)-knockout (KO) mice, from two weeks before the AAA induction by using a CaCl2 application on the abdominal aortae to the sacrifice date. Since Opg could bind to tumor necrosis factor-related apoptosis-inducing ligand (Trail) for inhibiting its activity, deficiency of the Opg gene has been reported to induce overactivation of the Trail induced-c-Jun N-terminal kinase (Jnk)/matrix metalloproteinase 9 (Mmp9) pathway in CaCl2-induced mouse AAA model, resulting in serious AAA progression. Here, we tested whether olmesartan could prevent AAA progression associated with Trail/Jnk/Mmp9 pathway.

Results:
We found that olmesartan prevented excessive aortic enlargement and serious degenerative change of the aortic tissue in Opg-KO mice at six weeks after AAA induction, but not affected AAA formation in wild-type mice. In Opg-KO mice, olmesartan reduced co-localized expression of phosphorylated Jnk and Mmp9 in the tunica media. Then, we tested whether Ang (1–7), the blood level of which is increased by ARB administration, is associated with the preventive effect of olmesartan, because Ang (1–7) had been reported to reduce the Jnk phosphorylation. Consistent with previous studies, olmesartan increased serum level of Ang (1–7) in our AAA model. In vascular smooth muscle cells, Ang (1–7) inhibited the phosphorylation of Jnk and the increase of downstream Mmp9 mRNA expression induced by Trail. Furthermore, administration of an Ang (1–7) antagonist, A779, to Opg-KO mice diminished the preventive effect of ARB against the AAA progression. Notably, olmesartan slightly lowered blood pressure in Opg-KO mice, while A779 did not affect the blood pressure-lowering effect of olmesartan.

Conclusions:
Our results indicate that ARB prevents the AAA progression in Opg-KO mice via the inhibition of Trail-induced Jnk-Mmp9 pathway. Furthermore, it is suggested that the increase of Ang (1–7) may play a key role in the preventive effect of ARB on the AAA progression.
PS-BPB01-7: ANGIOTENSIN II INDUCES AORTIC RUPTURE AND DISSECTION IN OSTEOPROTEGERIN-DEFICIENT MICE
Authors: Tsuruda Toshihiro , Yamashita Atsushi , Otsu Misa , Koide Masanori , Nakamichi Yuko , Hatakeyama Yoko Sekita , Hatakeyama Kinta , Funamoto Taro , Chosa Etsuo , Asada Yujiro , Udagawa Nobuyuki , Kato Johji , Kitamura Kazuo 
Published: January 2023

Background:
The biological mechanism of action for osteoprotegerin (OPG), a soluble decoy receptor for the receptor activator of nuclear factor kappa-B ligand (RANKL) in the vascular structure, has not been elucidated. The study aim was to determine if OPG affects aortic structural integrity in angiotensin II-induced hypertension.

Methods and Results:
Mortality was higher (P < 0.0001 by Log-rank test) in 8-week-old male homozygotes of OPG gene knockout (OPG
-/-
mice given subcutaneous administration of angiotensin II (1,000 ng/kg/min) for 28 days, with an incidence of 21% fatal aortic rupture (Chi-square, 8.024, P = 0.005), and 23% aortic dissection (Chi-square, 4.285, P = 0.038), than in age-matched wild type mice. The absence of OPG was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with 2.5-fold increased periostin expression and soluble RANKL concentrations. PEGylated human recombinant OPG administration decreased all-causes mortality (-22%, P < 0.001 by Log-rank test), the incidence of fatal aortic rupture (-13%, P = 0.08), and aortic dissection (-23%, P < 0.001) with decreasing numbers of elastin breaks (P = 0.0539) at the supra-renal aorta, periostin expressions (P = 0.0011), and soluble RANKL concentrations (P = 0.0012) in angiotensin II-infused OPG-/- mice.

Conclusions:
These data suggest that OPG protects against aortic rupture and dissection in Ang II-induced hypertension by inhibiting RANKL activity and periostin expression.
PS-BPB02-6: THE ROLE OF VEGFA G634C GENE POLYMORPHISM IN PREDICTING ADVERSE EVENTS DEVELOPMENT IN PATIENTS WITH ESSENTIAL HYPERTENSION AFTER STEMI
Authors: Kutia Inna , Rodionova Julia , Kopytsya Mikola , Shelest Boris 
Published: January 2023

The aim was to study the role of the polymorphism of the vascular endothelial growth factor A (VEGF A) gene (rs 2010963) in prognosis of adverse events in hypertensive patients with ST elevation myocardial infarction (STEMI) within 12 months

Design and method:
135 patients with STEMI were enrolled into the study, 109 (80.7%) male and 26 (19.3%) female, with an average age of 59.21 ± 8.92 years. The blood flow was restored at the level of TIMI III in patients included in the study. The VEGF A concentration was measured by the ELISA. The allelic polymorphism of the G634C of the VEGF A gene (2010963) was performed by a real time polymerase chain reaction (PCR) method. Blood examination was done on 7 days and 12 months after the STEMI.

Results:
The baseline levels of VEGF A was significantly higher 314.01 [159.94:627.66] pg/ml in patients with the GG genotype compared with those who had the GC genotype 221.28 [77.58–440.82] pg/ml, p = 0.045. After 12 months the level of VEGF A significantly increased from 221.28 [77.58:440.82]pg/ml to 424.56 [230.60–556.93] pg/ml (p = 0.0018) in patients with the GC group of polymorphic variant of the G634C gene. The peptide increased also in the patients with the GG gene but it was not significant. After one year examination, there were significant reduction in the level of systolic blood pressure (SBP) (p = 0.015) and diastolic blood pressure (DBP), (p = 0.031) in the patients with the genotype GC, at the same time in those with the GG genotype this reduction was also signidficant; p = 0.039 and p = 0.033 respectively.

Conclusion:
The STEMI patients with GC genotype are predisposed for the better prognosis compared to the GG genotype in the one year follow up period.
PS-BPB06-5: URINARY CELL TRANSCRIPTOMICS: A NON-INVASIVE EXPRESSION READOUT OF KIDNEY GENES OF RELEVANCE TO HYPERTENSION
Authors: Eales James M , Bogdanski Pawel , Wystrychowski Wojciech , Szczechowska Ewa Zukowska , Zywiec Joanna , Woolf Adrian S , Samani Nilesh J , Keavney Bernard , Charchar Fadi J , Tomaszewski Maciej 
Published: January 2023

Objective:
Hypertension affects 35% of the global adult population and is the leading preventable risk factor for premature death globally. The kidney is the key organ of blood pressure regulation in the body. Here, we compare the gene expression profile from renal cells shed naturally into the urine and kidney tissue to determine if urine can provide a non-invasive readout of kidney gene expression and whether hypertension-associated genes can be quantified in urine.

Design and Method:
Urinary cell and kidney tissue samples were collected from 33 human participants and were both profiled by poly-A RNA-sequencing, generating an average of 30 million paired reads per sample. These were quantified using the standard Genotype Tissue Expression (GTEx) project pipeline and were compared against 43 different human tissues and other bodily fluids using transcriptomic correlation. RNA-sequencing quality metrics were calculated by RNA-SeQC software. Gene set overrepresentation analysis for Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) employed Fishers exact test. Enriched and enhanced kidney genes were collected from the Human Protein Atlas (HPA).

Results:
Our RNA-sequencing metric analysis revealed that urinary cells can generate robust data of comparable or superior quality to that of saliva at similar read coverage. The top one hundred most highly expressed urinary cell genes show an enrichment for biological themes shared with the renal transcriptome, including immunity (P = 1.2x10–7), glucose metabolism (P = 1.3x10–5) and renal mineral reabsorption (P = 9.8x10–4). In an analysis all protein-coding genes across 43 human tissues/cell-types, urinary cells showed the highest level of transcriptomic correlation with kidney cortex (r2 = 0.65) and kidney medulla (r2 = 0.64). This correlation between urinary cells and kidney tissue was particularly strong (r2 = 0.72) in an analysis restricted to highly specific kidney genes (including uromodulin and the Na-K-Cl cotransporter NKCC2 [loop diuretic target]). 98% (176 out of 179) of kidney genes with a known causal association to blood pressure were expressed in urinary cells. Their urinary expression demonstrated strong correlation with their abundance in kidney cortex (r2 = 0.68) and medulla (r2 = 0.64).

Conclusions:
Standard poly-A RNA-sequencing of cells harvested from urinary sediments produces robust gene expression profiles. These profiles provide a non-invasive insight into transcriptome of the kidney and permit measuring expression of kidney genes of relevance to BP regulation and hypertension.
PS-BPB08-1: ANGIOTENSIN II AT1A RECEPTORS IN THE PROXIMAL TUBULES PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF TWO-KIDNEY, ONE-CLIP GOLDBLATT HYPERTENSION
Authors: Li Xiao Chun , Hassan Rumana , de Oliveira Leite Ana Paula , Dugas Courtney , Sato Akemi , Sato Ryosuke , Zhuo Jia Long 
Published: January 2023

Objective:
It is well recognized that the activation of the renin-angiotensin system (RAS) in the clipped kidney plays a critical role in the development of two-kidney, one-clip Goldblatt hypertension (2K1C) in animal models, but the roles of intratubular angiotensin II (Ang II) AT1 (AT1a) receptors and its downstream target, Na+/H+ exchanger 3 (NHE3) in the proximal tubules have not been determined previously. In the present study, we tested the hypothesis that genetic deletion of AT1a receptors selectively in the proximal tubules of the kidney attenuates the development of 2K1C Goldblatt hypertension via AT1a receptor-mediated, Na+/H+ exchanger 3 (NHE3)-dependent mechanisms.

Design and Methods:
To test the hypothesis, 2K1C Goldblatt hypertension was induced by placing a silver clip, 0.12 mm internal diameter, on the left renal artery for 4 weeks in adult male and female wild-type (WT), global AT1areceptor knockout (Agtr1a-/-
), proximal tubule (PT)-specific Agtr1a-/-
(PT-Agtr1a-/-
), or PT-Nhe3-/-
mice, respectively.

Results:
Systolic blood pressure increased in a time-dependent manner reaching a maximal response by Week 2–3 in wild-type mice (Basal: 112 ± 2 vs. 2K1C: 149 ± 4 mmHg, n = 12, P < 0.01). 2K1C Goldblatt hypertension in WT mice was associated with significant increases in renin mRNA expression in the clipped kidney (Control: 2066 ± 255 vs. Clipped: 3144 ± 569 copies/ng RNA, P < 0.01), and decreases in renin mRNA expression in the nonclipped right kidney (1738 ± 341 copies/ng RNA, P < 0.05). Plasma Ang II levels were significantly increased in WT mice with 2K1C Goldblatt hypertension (Control: 50.2 ± 7.2 vs. 2K1C: 109.7 ± 17.2 pg/ml, P < 0.05). Glomerular and tubulointerstitial fibrotic responses were also significantly increased in the clipped kidney (P < 0.01). In contrast to WT mice, the development of 2K1C hypertension was completely attenuated in global Agtr1a-/-
(Basal: 88 ± 4 vs. 2K1C: 92 ± 2 mmHg, n = 9, n.s.), PT-Agtr1a-/-
mice (Basal: 101 ± 2 vs. 2K1C: 104 ± 4 mmHg, n = 12, n.s.), or PT-Nhe3-/-
mice (Basal: 103 ± 3 vs. 109 ± 5 mmHg, n.s.). Renin mRNA expression was not different in clipped and nonclipped kidney of Agtr1a-/-
mice, but it was decreased in the nonclipped kidney of PT-Agtr1a-/-
mice (P < 0.05).

Conclusions:
Taken together, our results suggest that the activation of intratubular RAS in the proximal tubules and increase of NHE3-mediated proximal tubular Na+ reabsorption play a key role in the development of 2K1C Goldblatt hypertension in mice.
PS-BPB08-4: IMPAIRED TCA CYCLE METABOLISM IN DIABETIC NEPHROPATHY IS LINKED TO ALBUMINURIA AND KIDNEY INJURY
Authors: Azushima Kengo , Kovalik Jean Paul , Yamaji Takahiro , Gurley Susan Bailey , Coffman Thomas Myron 
Published: January 2023

Objective:
Recent work has highlighted potential contributions of impaired renal energy metabolism, including mitochondrial dysfunction and altered fatty acid metabolism, in chronic kidney diseases including diabetic nephropathy (DN). However, causal connections between specific metabolic abnormalities and pathophysiology of DN have been difficult to establish. Here, we approach this question using a mouse model recapitulating characteristic features of human DN and a targeted metabolomics platform designed to assess key metabolic pathways involving amino acids, fatty acids, glycolysis and the TCA cycle.

Design and method:
We generated a mouse model of DN with underlying activation of the renin-angiotensin system (RAS) by a renin transgene (R) driven by the albumin promoter on the Akita background of type I diabetes (A). We have shown that on a susceptible 129/Sv background, Akita-ReninTg (AR) mice exhibit cardinal characteristics of human DN including high-grade albuminuria and glomerulosclerosis, whereas AR mice on a C57BL/6 background do not develop DN. To assess the impact of genetic background on energy metabolism in DN, kidneys from 24-week-old male AR mice on both backgrounds were evaluated by the targeted metabolome analysis. To further distinguish the impact of RAS activation on relevant pathways associated with kidney disease development, 12-week-old male 129/Sv AR mice were treated with the angiotensin receptor blocker (ARB) losartan 10 mg/kg/day for 12 weeks. 24-hour urine samples were collected in metabolic cages and urine albumin levels were measured by EIA. Kidneys from age-matched parental 129/Sv and C57BL/6 wild-type mice were analyzed as controls.

Results:
A distinct metabolic profile was observed in kidneys of DN-susceptible 129/Sv AR mice including reduced levels of C2 acetyl-carnitine that reflect a deficiency in acetyl-CoA, perturbations of TCA cycle intermediates and increased lactate levels. In addition, levels of phosphorylated-AMPK were reduced. These metabolic changes were absent in DN-resistant C57BL/6 AR mice. Treatment of 129/Sv AR mice with the ARB dramatically reduced albuminuria (906 ± 169 vs 193 ± 42 μg/day, p < 0.01) and attenuated kidney pathology while restoring levels of C2 acetyl-carnitine, TCA intermediates, lactate and phosphorylated-AMPK toward normal. ARB treatment also increased kidney ATP content. In 129/Sv mice, there were statistically significant correlations between albuminuria and kidney levels of lactate, acetyl-carnitine, citrate and succinate.

Conclusions:
Thus, there is a distinct profile of impaired energy metabolism associated with DN susceptibility that is attenuated by RAS blockade. Impaired TCA cycle function and coincident increases in lactate are linked to albuminuria in mice with DN, and may contribute to kidney injury.