bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B05-4: COMPARATIVE EFFECTS OF RENAL DENERVATION IN DIFFERENT STAGES OF HYPERTENSION ON CARDIAC, RENAL, AND ADIPOSE PATHOLOGY IN DAHL SALT-SENSITIVE RATS
Authors: Nagata Kohzo , Tagami Kaito , Okuzawa Toko , Hayakawa Misaki , Nomura Akane , Nishimura Tomo , Furukawa Nozomi , Sakabe Nanako , Ikeda Katsuhide , Kobuchi Shuhei , Kitada Kento , Fujisawa Yoshihide , Nishiyama Akira , Murohara Toyoaki 
Published: January 2023

Objective:
Renal denervation (RDN) has emerged as a novel therapy for resistant hypertension. In Dahl salt-sensitive (DahlS) rats, RDN does not prevent the development of hypertension but attenuates the progression of hypertension. We have now investigated the comparative effects of RDN in early versus advanced stages of hypertension on cardiac, renal, and adipose tissue pathology in DahlS rats.

Design and method:
Male DahlS rats fed an 8% NaCl diet after 6 weeks of age were subjected to RDN or sham surgery at 7 (early stage) or 9 (advanced stage) weeks. In the RDN groups, all visible nerves along the vessels were cut and the vessels were painted with a solution of 10% phenol in absolute ethanol. In contrast, in the sham-operated groups, the kidneys were exposed but the vessels were not stripped or coated with phenol. At 12 weeks, left ventricular (LV), renal, and adipose tissue were excised for analysis.

Results:
Successful RDN was confirmed by determination of renal norepinephrine content in each rat subjected to RDN less than 10% of the mean values of those in the sham-operated groups. Although both stages of RDN modestly attenuated blood pressure elevation, they improved LV diastolic function and fibrosis and attenuated macrophage infiltration and expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) genes in the heart, to a similar extent. In addition, both stages of RDN similarly reduced macrophage infiltration in glomeruli, the glomerulosclerosis index, the tubulointerstitial injury score as well as expression of MCP-1 and TNF-α genes in the kidney. The early stage group showed reductions in both retroperitoneal fat mass and adipocyte cross-sectional area, whereas the advanced stage group did an increase in fat mass without any change in adipocyte size.

Conclusions:
Both early and advanced stages of RDN mildly attenuated hypertension as well as ameliorated cardiac and renal injury, to a similar extent, in salt-loaded DahlS rats. The anti-hypertensive effect of RDN is thus likely attributable primarily to improved renal pathology. These results also suggest a possible crosstalk among the kidney, cardiovascular system, and adipose tissue via neural mechanisms in salt-sensitive hypertension.
PS-B05-12: ANTIHYPERTENSIVE AND CARDIO-PROTECTIVE POTENTIAL OF O. SANCTUM LEAVES EXTRACT IN L-NAME INDUCED HYPERTENSIVE RATS
Authors: Kumar Abhishek , Sharma Bechan 
Published: January 2023

Objective:
There are approximately 26% of adults in the world who suffer from hypertension, which is the most common cardiovascular disease. Essential hypertension is mainly caused by endothelial dysfunction which results from nitric oxide (NO) deficiency. The present study sought to determine the impact of O. sanctum leaf extract (OS) in protecting against L-NAME induced hypertension and oxidative stress in wistar rats.

Design and method:
A non-specific nitric oxide inhibitor, L-NAME, (40 mg/kg/day), was administered to male Wistar rats to induce hypertension. CoQ10 was used as a standard anti-hypertensive compound. All of the other groups received L-NAME combined with OS extract (200 mg/kg/day) orally for three weeks. Following the treatment, hemodynamic parameters were measured using direct cannulation. The lipid profile, kidney and cardiac functions, as well as markers of oxidative stress were evaluated. The results were expressed as mean ± SD.

Results:
L-NAME was found to cause high blood pressure, NO depletion, oxidative imbalance and damage in cardiac and kidney function in animals. The Cardiac markers enzyme level were significantly increased in L-NAME only group whereas, the CO-treatment group had lower lower of Cardiac markers as compared to control as well as L-NAME group. In hypertensive rats, OS treatment significantly lowers the expression of angiotensin converting enzyme (ACE) and mineralocorticoid receptor expression in hypertensive rats. Concurrent treatment with L-NAME and OS extract prevented the all injuries without affecting the heart rate or raising blood pressure.

Conclusions:
The results confirm O. Sanctum leaves extract antihypertensive action and indicate its protective properties in the L-NAME induced hypertension model of rats, likely due to the presence of rich antioxidant potential and by inhibiting the inflammation.
PS-B07-4: ADMINISTRATION OF AMINO ACIDS PROVOKES EXPRESSION OF PRO-FIBROTIC GENES IN MURINE CULTURED FIBROBLAST CELLS
Authors: Oshida Takuma , Miyashita Kazutoshi , Kubo Akiko , Sato Masaaki , Fujii Kentaro , Ryuzaki Masaki , Uto Asuka , Nakamura Toshifumi , Kinouchi Kenichiro , Kobayashi Sakiko , Ito Hiroshi 
Published: January 2023

Objective:
Diabetic kidney disease (DKD) has been the most common cause of end-stage renal disease (ESRD) which leads to hemodialysis for more than 20 years in Japan. Various reports have been published on the mechanisms underlying the progression of DKD, however, many details remain unclear. We investigated the mechanisms underlying the progression of renal fibrosis and kidney injury in hyperglycemia from the viewpoint of metabolic alteration in the kidney by using streptozotocin-treated mice (STZ mice).

Design/Methods:
8 weeks old ICR mice were treated with streptozotocin (200 mg/kg intra-peritoneally), to produce type 1 diabetes mellitus model mice. The kidneys of those mice were collected 4 weeks after STZ treatment and examined for metabolites that were altered in the kidneys of STZ mice by metabolome analysis. Amino acids that were increasing in the kidneys of STZ mice were administered to L929 murine fibroblast cells, and expression of pro-fibrotic genes were examined.

Results:
STZ-treatment caused progression of renal fibrosis in mice under both low- and high-protein diets. Metabolome analysis of the kidneys in STZ mice showed marked alterations of amino acids in the kidneys. Increased levels of branched chain amino acids (BCAAs) such as valine and leucine were observed. Among these amino acids, leucine administration to L929 cells resulted in increased expression of genes promoting renal fibrosis.

Conclusions:
Alterations of BCAAs in the kidneys due to hyperglycemia in STZ mice may affect progression of renal fibrosis and kidney injury. We are now investigating the mechanism by which BCAAs contribute to renal fibrosis.
PS-B07-6: L-ARGININE SUPPLEMENTATION SUBSTANTIALLY ATTENUATES HYPERTENSION BUT NOT CARDIAC INJURY IN RATS WITH METABOLIC SYNDROME
Authors: Tagami Kaito , Okuzawa Touko , Hayakawa Misaki , Cui Xixi , Obara Natsuki , Kunimatsu Asuko , Koide Mayako , Teranishi Tamami , Furukawa Nozomi , Sakabe Nanako , Ikeda Katsuhide , Murohara Toyoaki , Nagata Kohzo 
Published: January 2023

Objective:
L-arginine is not only a building block for protein but also a physiological substrate for the synthesis of nitric oxide (NO) and plays a regulatory role in signal transduction pathways in cells. Dietary L-arginine supplementation reduced fat mass both in Zucker diabetic fatty rats and in diet-induced obese rats. However, little is known about the effects of L-arginine on cardiac morphology and function in metabolic disorders. We have now examined the effects of L-arginine on cardiac pathology in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS).

Design and method:
DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified control diet and were supplemented with 0.50% L-arginine-HCl or 0.85% L-alanine (isonitrogenous control) in drinking water from 13 to 17 weeks of age.

Results:
L-arginine supplementation did not affect body weight, visceral and subcutaneous fat mass, insulin resistance, or food and water intake in DS/obese rats, but substantially alleviated hypertension. However, left ventricular (LV) and cardiomyocyte hypertrophy and the upregulation of myocardial fetal-type gene expression, macrophage infiltration in the heart, and increased perivascular and interstitial fibrosis of the LV myocardium and the upregulation of fibrosis-related gene expression were not improved by such intervention. Additionally, L-arginine did not ameliorate impairments of Doppler- or micromanometer-derived indices of LV diastolic function. None of these parameters were influenced by L-arginine supplementation in DS/lean rats.

Conclusions:
L-arginine supplementation substantially ameliorated hypertension but did not attenuate LV remodeling or diastolic dysfunction in this model of MetS. These data suggest that in addition to its role as a precursor of NO, L-arginine may play a role as a functional amino acid that modulates growth and inflammation.
PS-B08-7: L-CARNITINE AMELIORATES DIABETIC KIDNEY DISEASE BY ALLEVIATING MITOCHONDRIAL ABNORMALITY IN SDT-FATTY RATS
Authors: Ito Sakuya , Taguchi Kensei , Kaida Yusuke , Kodama Goh , Moriyama Tomofumi , Yokota Yunosuke , Shinohara Masami , Tashiro Kyoko , Fukami Kei 
Published: January 2023

Background and Aims:
Abnormal fatty acid metabolism is associated with the progression of diabetic kidney disease (DKD). Carnitine plays a central role in β;-oxidation and energy production by transporting long-chain fatty acids from the cytoplasm to the mitochondria. Recently, we found that significant ectopic fat was accumulated in the kidney tissue in DKD patients compared with those in minimal change kidney disease patients. Juvenile visceral steatosis (jvs) mice, described as an animal model for systemic carnitine deficiency, introduce a marked ectopic fat accumulation in the kidney. These findings suggest that abnormal carnitine dynamics in DKD cause ectopic fat accumulation due to abnormality of the fatty acid metabolism. However, the association between abnormalities of carnitine metabolism and the progression of DKD is unknown.

Method:
Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model was used. Unilateral nephrectomy was performed and 0.3% salt water was administered at 6 weeks of age, and created a renal dysfunction model in SDT fatty rat (DKD model). Age-matched male Sprague-Dawley (SD) rat was used as a control. Experiment 1: We compared 3 groups; SD rats (n = 8), SDT fatty rats (n = 8), DKD rats (n = 8). Experiment 2: We compared 3 groups; SD rats with sham operation (n = 8), DKD rats (n = 7), DKD rats treated with L-carnitine administration (0.75% L-carnitine diet) for 10 weeks (n = 6). All rats were sacrificed at 17 weeks old. Carnitine was measured by the enzyme cycling method. Acylcarnitine was analyzed by the tandem-mass spectrometry.

Results:
Plasma and renal free carnitine levels and short/middle-long chain acylcarnitine ratio were significantly decreased in DKD rats compared with those in SD and SDT fatty rats. The renal expression levels of organic cation / carnitine transporter 2 (OCTN2), carnitine palmitoyl transferase 1a (CPT1a), CPT2 and carnitine acetyltransferase (CrAT) were significantly decreased in DKD rats compared with those in SD and SDT fatty rats. Similarly, peroxisome proliferator-activated receptor γ co-activator 1α (PGC1α) activity was decreased in DKD rats. L-carnitine administration significantly improved renal function, urinary albumin excretion, interstitial fibrosis and renal ectopic fat accumulation in DKD model rats. L-carnitine administration ameliorated the decrease of renal OCTN2, CPT1a, CPT2 and CrAT protein expression, and significantly improved PGC1α activity in DKD model rats. Furthermore, L-carnitine administration mitigated lipid peroxidation and mitochondrial dysfunction in DKD rats.

Conclusion:
L-carnitine administration might be a promising therapeutic strategy for improving renal function by alleviating mitochondrial dysfunction in DKD rat model.
PS-B08-9: INHIBITION OF PERIOSTIN PROTECTED FROM EXACERBATION OF INFLAMMATION IN RHABDOMYOLYSIS-INDUCED ACUTE KIDNEY INJURY
Authors: Muratsu Jun , Taniyama Yoshiaki , Sanada Fumihiro , Shibata Kana , Koibuchi Nobutaka , Rakugi Hiromi , Morishita Ryuichi 
Published: January 2023

Objective:
Rhabdomyolysis is the breakdown of damaged skeletal muscle and the leakage of muscle-cell contents, including myoglobin, and other sarcoplasmic proteins into the circulation. These products may be filtered through the glomeruli, leading to acute kidney injury (AKI) via several mechanisms, such as inflammation and intratubular obstruction secondary to protein precipitation. New therapeutic strategy to lessen AKI are urgently needed. Thus far, several cellular pathways, nuclear factor kappa beta (NF-KB) as well as including pro-inflammatory effects on epithelial and tubular epithelial cells, have been identified as the major avenues for the initiation of the matrix-producing cells in AKI. Recently, it is suggested that periostin, extracellular matrix, is involved in the development of inflammation through the modulation of NF-KB pathway. However, periostin on the progression of the inflammation protection in AKI due to rhabdomyolysis is unclear. This study aimed to investigate the role of periostin in a rhabdomyolysis mice model of AKI.

Design and method:
In vivo, rhabdomyolysis-induced AKI was created by an intramuscular injection of 50% glycerol (5 mg/kg body weight). The expression level of periostin during the progression of acute renal failure after glycerol intramuscular injection for C57BL/6J wild type (WT) mice model was investigated. The mice were sacrificed at 72 hours after glycerol injection. We have developed periostin null mice to examine the role of periostin on acute renal failure. The role of periostin were further investigated through in vitro methods. In vitro, the development of renal inflammation is associated with NF-KB pathway. To investigate the function of periostin, we administrated Hemin(100uM) on NIH-3T3 fibroblast cells and the subsequent signaling pathways was examined.

Results:
The expression of periostin was highly increased, peaking at approximately 72 hours after gycerol injection. Inflammation-associated mRNA such as Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha and IL6 expression and tubular injury score in H-E staining was more reduced in periostin null mice than WT mice at 72 hours after gycerol injection. Finally, an intraperitoneal injection of periostin antibody suppressed the mortality. These findings suggest a causal link between periostin and inflammation in AKI induced by rhabdomyolysis. In addition, an intraperitoneal injection of antibody for periostin antibody might be a new therapeutic strategy against the development of AKI induced by rhabdomyolysis.

Conclusions:
Periostin were highly expressed in kidney via rhabdomyolysis, and were a positive regulator of AKI. Targeting periostin might offer a new therapeutic strategy against the development of renal failure.
PS-B08-10: COMBINATION OF SYSTEMIC ATRAP DEFICIENCY WITH ANGIOTENSIN II STIMULATION ACCELERATES THE DEVELOPMENT OF DIABETIC NEPHROPATHY IN STREPTOZOTOCIN TREATED MICE
Authors: Taguchi Shinya , Azushima Kengo , Wakui Hiromichi , Suzuki Toru , Urate Shingo , Abe Eriko , Tanaka Shohei , Tsukamoto Shunichiro , Tamura Kouichi 
Published: January 2023

Objective:
One of the obstacles toward understanding the pathophysiology of diabetic nephropathy (DN) has been the lack of reliable animal models that faithfully replicate features of human DN. Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) promotes internalization of AT1R from the cell surface into the cytoplasm, resulting in the suppression of AT1R signaling pathway. We have recently reported that systemic ATRAP deficiency exaggerates streptozotocin (STZ)-induced DN via an activation of renal renin-angiotensin system (RAS) (Haruhara K, et al. Kidney Int 2022). However, STZ-induced diabetic ATRAP knockout mice still exhibited a modest increase in albuminuria with limited pathological changes just in glomerulus. To establish more robust DN models, we examined the effect of Ang II stimulation on the development of DN in STZ-treated ATRAP knockout mice.

Design and method:
Male eight weeks old C57BL/6 mice (Ctrl) and systemic ATRAP-knockout mice (KO) were divided into three groups: 1) Ctrl-STZ, 2) Ctrl-STZ-Ang II, and 3) KO-STZ-Ang II. Hyperglycemia was induced by intraperitoneal injection of 55 mg/kg STZ for consecutive 5 days. From 4 weeks after STZ administration, Ang II (1000 ng/kg/min) was continuously administered by osmotic mini-pumps for 6 weeks. During the experimental period, body weights and levels of blood glucose were measured every 2 weeks. At 6 and 10 weeks after STZ administration, 24-hour urine samples were collected in metabolic cages, and urinary albumin excretion (UAE) was evaluated by ELISA. At the end of experimental period, mice were euthanized to evaluate renal pathological changes.

Results:
During the experimental period, body weight gain and levels of blood glucose were not significantly different between the three groups. Nonetheless, although levels of UAE at 6 weeks after STZ administration were still modest and comparable between the three groups, levels of UAE only in the KO-STZ-Ang II group were remarkably increased compared to those in the Ctrl-STZ and Ctrl-STZ-Ang II groups at 10 weeks after STZ administration (679.1 ± 583.7 vs 69.9 ± 10.0 vs 61.3 ± 8.2 μg/day, respectively). Furthermore, in the KO-STZ-Ang II group, exacerbation of mesangial expansion and interstitial fibrosis was observed.

Conclusions:
In STZ-induced diabetic mice, combination of systemic ATRAP deficiency with Ang II stimulation accelerated the development of DN, suggesting a potential to become a promising mouse model replicating key features of human DN.
PS-B08-12: THE REGULATORY EFFECTS OF HYPERTENSION-RELATED CIRCULAR RNA GRB10 IN THE KIDNEY
Authors: Maier Michelle Carla , Woods Bradley , Prestes Priscilla , Byars Sean , Eales James , Tomaszewski Maciej , Charchar Fadi 
Published: January 2023

Objective:
To examine the effects of experimental reduction in the expression of circGRB10 in human kidney cells and identify its potential regulatory targets in human kidney cells.

Design and method:
Through use of small interfering RNA (siRNA), we knocked-down circGRB10 in human kidney cells (HEK293) and investigated potential downstream targets using RNA sequencing. Small RNA sequencing and total RNA sequencing were performed to investigate differentially expressed microRNAs (miRNAs) and mRNAs, respectively. Statistical significance was set as FDR < 0.01. Pathway analysis was performed using Kyoto Encyclopedia for Genes and Genomes (KEGG) on the Database Annotation Visualization Integrated Discovery (DAVID). Finally, we investigated enriched gene ontology terms.

Results:
We identified 1,483 genes showing differential expression between cells where circGRB10 was knocked down and the control cells. No miRNAs were differentially expressed between circGRB10 cells and the control. The differentially expressed genes mapped onto 66 KEGG pathways including those of relevance to protein and RNA binding.

Conclusion:
These results indicate that circGRB10 most likely operates as a direct regulator of mRNA expression in the kidney rather than through modulation of microRNAs.
PS-B09-4: SHORTER LEUKOCYTE TELOMERE LENGTH AS AN EARLY INDICATOR FOR CHRONIC KIDNEY DISEASE IN HYPERTENSIVE PATIENTS
Authors: Akinnibosun Olutope Arinola , Eales James , Nguyen Huy , Bogdanski Pawel , Szczechowska Ewa Zukowska , Denniff Matthew , Tomaszewski Maciej , Charchar Fadi 
Published: January 2023

Objective:
Essential hypertension is a major risk factor for incident chronic kidney disease (CKD). This is a main reason for preference of antihypertensive medications that provide some protection against hypertension induced renal damage. Furthermore, there is abundant evidence that hypertension and CKD comorbidity worsens cardiovascular disease prognosis with increased morbidity and mortality. Onset of CKD may not be noticeable until there is evident progressive decline in the estimated glomerular filtration rate (eGFR). For this, telomere attrition may provide some early indication. Telomeres are markers of biological aging, and telomere attrition is associated with oxidative stress and inflammation. Kidney interstitial inflammation is known to play a central role in loss of renal function progressing into CKD. This study investigated the association between telomere length and renal interstitial inflammation in hypertensive patients.

Design and Methods:
Our study group consisted of 200 participants from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study. Interstitial inflammation in human kidney tissue samples was assessed by histology. eGFR was calculated from serum creatinine using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) FORMULA. Leukocyte telomere length (LTL) was quantified using quantitative polymerase chain reaction.

Results:
Mean LTL was significantly shorter in hypertensive participants (2.776 ± 0.063) compared with non-hypertensive participants (3.007 ± 0.092; P = 0.041). In hypertensive participants without CKD, renal interstitial inflammation negatively associates with leukocyte telomere length (LTL) (r = -0.483, P = 0.048), and the association remained significant after adjustment for age (r = -0.479, P = 0.041). Similar results were observed after exclusion of patients with eGFR > = 60 ml/min/1.73m2. In patients with eGFR < 60 ml/min/1.73m2, the association remained significant after adjusting for age, sex, BMI, diabetes mellitus and smoking status (r = -1.429, P = 0.011). These results show that telomere length associates with interstitial inflammation in hypertensive patients with no apparent decrease in eGFR.

Conclusions:
Hypertensive participants have shorter LTL than non-hypertensive participants, and within the hypertensive group, participants with shorter telomeres are more likely to have CKD. Telomere length may provide suitable indication to help target hypertensive patients at increased risk of developing CKD.