bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in arterial stiffness and sympathetic activity in older CKD patients
Authors: Zanuzzi Matias , Jeong Jinhee , DaCosta Dana , Park Jeanie 
Published: May 2023

Chronic kidney disease (CKD) is characterized by sympathetic nervous system overactivity that contributes to increased arterial stiffness and cardiovascular risk. While premenopausal females are relatively protected from cardiovascular disease in healthy individuals, older postmenopausal females without kidney disease have similar degrees of sympathetic overactivity, vascular stiffness and cardiovascular risk compared to older age-matched males in the general population. However, in the CKD population, cardiovascular mortality risk remains higher in older males compared to age-matched females and whether sex differences in neural and vascular function exist in older CKD patients is unknown. Therefore, we tested the hypothesis that compared to older females, older males with CKD have higher baseline sympathetic activity that is related to increased arterial stiffness. In 207 CKD patients (N=90 females, 62 ± 9 years; and N=117 males, 60 ± 9 years), we measured resting sympathetic nerve activity directed to muscle (MSNA) by microneurography at the peroneal nerve. At a separate visit, arterial stiffness was determined by carotid-to-femoral pulse wave velocity (PWV) using transcutaneous Doppler flow velocity (SphygmoCor®). Office blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM; Spacelabs) were performed using standard techniques. Resting MSNA was higher in males versus females with CKD (43 ± 10 vs 31 ± 14 bursts/min; p= 0.039). Both office and 24-hour ambulatory diastolic BP (79 ± 11 vs 67 ± 14 mmHg, p<0.001) and mean arterial pressure (96 ± 10 vs 88 ± 13 mmHg, p<0.001) were also higher in males versus females. PWV was not different between male and female groups (p= 0.157). There was no association between PWV and resting MSNA in males, while in females, there was an inverse relationship between PWV and MSNA burst frequency (r2=0.271; p=0.039) and burst incidence (r2=0.310; p=0.025). Older male CKD patients have higher resting MSNA, office and ambulatory BP compared to older females with CKD. In contrast, there were no differences in arterial stiffness measured as PWV between sexes. In males, increased MSNA was not associated with increased arterial stiffness, while MSNA was negatively correlated with PWV in females. Sex differences in neural and vascular function may impact cardiovascular outcomes in older patients with CKD. Supported by NIH grants R01HL135183, R33AT010457. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Resveratrol supplementation improves endothelial function in chronic kidney disease
Authors: Gimblet Colin , Kruse Nicholas , Geasland Katharine , Mickelson Jeni , Sun Mingyao , Rehman Safur , Wendt Linder , Ten-Eyck Patrick , Ernst Jackson , Pierce Gary , Jalal Diana 
Published: May 2023

Introduction: Chronic kidney disease (CKD) associates with increased risk of cardiovascular disease (CVD), in part, due to lower endothelial function. Thus, interventions that increase endothelial function could mitigate CVD in CKD. Resveratrol is a polyphenol that improves endothelial function in obese and aging adults. Whether resveratrol supplementation increases endothelial function in patients with CKD is unknown. Our objective was to test the effects of resveratrol supplementation on endothelial function in CKD. We hypothesized that resveratrol supplementation would increase endothelial function in patients with CKD. Methods: 25 adults with stage 3 CKD and type 2 diabetes were enrolled in a randomized, double-blind, placebo-controlled, crossover study to investigate the effects of 6-week resveratrol supplementation (400 mg/day) on endothelial function. Endothelial function was assessed via brachial artery flow-mediated dilation (BA-FMD). Vascular smooth muscle reactivity was determined from nitroglycerin-mediated dilation. Estimated glomerular filtration rate (eGFR) was calculated from serum cystatin C using the CKD-EPI formula. A mixed effects generalized linear model was used to evaluate differences in treatment arms over time. Results: The median age of the subjects was 70 (67, 74) years and 86% of the patients were male. The mean (SD) GFR and hemoglobin A1c were 42(9) ml/min/1.73m2 and 7.36(0.77)%, respectively. Within-group comparisons revealed BA-FMD increased by 0.91% after resveratrol supplementation (p=0.002), but not placebo (p=0.44), and between-group comparisons indicate resveratrol increased BA-FMD greater than placebo (p=0.001). Nitroglycerin mediated dilation was unchanged after both resveratrol supplementation and placebo (p>0.05). GFR, hemoglobin A1c and blood pressure were unchanged following resveratrol supplementation suggesting that other mechanisms may underlie resveratrol-mediated benefits on endothelial function in this study. Conclusion: Resveratrol supplementation increases endothelial function in patients with CKD. Larger clinical trials for longer duration are needed to confirm our findings and to evaluate the mechanisms by which resveratrol improves endothelial function in CKD. Funding: This study was supported by the Renal Hypertension Training Grant (NIH NRSA T32 award) and Dr. Jalal's grant R01HL134738-01A1. Colin Gimblet is supported by the American Heart Association predoctoral fellowship grant (23PRE1012593). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Maternal obesity suppresses embryonic myogenesis via enhancing H19 lncRNA expression
Authors: Gao Yao , Zhao Liang , Liu Xiangdong , Hossain Md Nazmul , de Avila Jeanene M. , Du Min 
Published: May 2023

Background: Maternal obesity (MO) impairs fetal skeletal muscle development, which programs long-term metabolic dysfunction of offspring muscle, but the underlying mechanisms remain poorly defined. Gene imprinting is an allelic epigenetic modification derived from gametes, resulting in gene expression only from one parental allele. H19, the first discovered imprinting gene, is a paternally imprinted and maternally expressed long non-coding long RNA (lncRNA). H19 is highly expressed in placental and fetal tissues but rapidly downregulated after birth except skeletal muscle, underscoring its roles in regulating muscle development. Up to now, the regulatory roles of H19 in prenatal myogenesis and muscle development affected by MO remain to be examined. We hypothesized that MO suppresses embryonic myogenesis by altering H19 expression. Method: High-fat diet (45% calories from the fat) was used to induce MO in mice. Briefly, total 32 of C57BL/6 mice (8-week-old) were randomly chosen and divided into control (CT, chow diet, n=16) and MO (n=16) groups. After 2-month feeding, female mice were mated with age-matched males. Successful mating was confirmed by the presence of vaginal plug. Embryos were collected at E11.5. To analyze allelic expression, CAST/EiJ mice were crossed with C57BL/6, which resulted in 8 single nucleotide polymorphisms (SNPs) between two alleles at the H19 gene. Single cell-RNA sequencing (scRNA-seq) was conducted using E11.5 embryos. To analyze its mediatory role, H19 was overexpressed in P19 cells and the resulting myogenesis was analyzed. Results: MO mice were 23% heavier than the CT group. MO embryos displayed suppressed muscle development, shown by reduced myogenic genes expression. Both scRNA-seq and RT-qPCR showed that H19 expression was increased in MO embryos. The imprinting pattern of H19 was disrupted, showing a bi-allelic expression of H19. To establish causality, we overexpressed H19 in cells which strongly inhibited myogenesis, indicated by lower myogenic genes expression and less myotube formation. Conclusion: MO impedes embryonic myogenesis by elevating H19 expression. The imprinting of H19 in the paternal allele was disrupted by MO, resulted in H19 expression from both maternal and paternal alleles. R01HD067449 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The impact of aortic valve regurgitation on the combination therapy of VA-ECMO and Imeplla support in severe cardiogenic shock: a simulation study
Authors: Matsushita Hiroki , Nishikawa Takuya , Yokota Shohei , Kakuuchi Midori , Yokoi Aimi , Nishiura Akitsugu , Unoki Takashi , Meihua Li , Uemura Kazunori , Kawada Toru , Saku Keita 
Published: May 2023

Background: The utilization of a combination of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, ECPELLA, has become widespread among patients with cardiogenic shock. The utilization of VA-ECMO in the presence of aortic regurgitation (AR) can result in significant left ventricular (LV) distention. Additionally, the implantation of Impella via the aortic valve frequently induces AR clinically. We established a simulation model and evaluated the impact of AR on hemodynamics under ECPELLA. Furthermore, assuming that the reverse flow of AR is strongly determined by aortic pressure (AP) level, we simulated a scenario where AP was further decreased. Methods: We employed Simulink® (Mathworks, Inc.). The systemic and pulmonary circulations were modeled using a 5-element resistance-capacitance network. Four cardiac chambers were represented by time-varying elastance. We compared the aortic regurgitant flow (Far), total systemic flow (Ftotal), and LV pressure-volume relationship under various severities of AR and varying Impella (0-3.7 L/min) and VA-ECMO (0-5 L/min) flows. AR grades were adjusted by the regurgitant resistance and classified as mild, moderate, and severe, mimicking a clinical scenario. Results: Without AR, ECMO significantly increased Ftotal and raised LV end-diastolic pressure (LVEDP). Impella increased Ftotal and decreased LVEDP. The concomitant presence of AR exacerbated the increase of LVEDP by ECMO and the reduction of LVEDP by Impella. Under ECPELLA support (VA-ECMO: 3 L/min) with mild AR, the increase of Impella support (1 to 3.5 L) increased Ftotal and Far, while decreasing LVEDP, indicating the prevention of AR-induced LV distention. Additionally, the presence of mild AR prevented the Impella-induced left ventricular suction that is commonly observed under ECPELLA support with high-flow VA-ECMO. In the case of moderate AR, while the hemodynamic trends were similar to those observed under mild AR, Impella was unable to prevent the increment of LVEDP to a critical level (< 20 mmHg). However, by decreasing AP through reducing resistance (e.g. vasodilators), both Far and LVEDP were dramatically reduced and Ftotal was increased under ECPELLA support. Conclusion: The concomitant presence of AR in ECPELLA condition increased LV load, while prevented LV suction. The use of vasodilator in ECPELLA with AR could attenuate AR, increase systemic perfusion, and reduce LV load. The optimal control of Impella and VA-ECMO flows and AP can maximize the hemodynamic and LV unloading impacts of ECPELLA. no funding This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Endothelial Specific Deletion of Autotaxin Improves Stroke Outcomes
Authors: Panchatcharam Manikandan , Bhattarai Susmita , Subedi Utsab , Manikandan Shrivats , Sharma Sudha , Sharma Papori , Miller Chole , Bhuiyan Md Shenuarin , Kidambi Srivatsan , Aidinis Vassilis , Sun Hong , Miriyala Sumitra 
Published: May 2023

Autotaxin (ATX) is an extracellular secretory enzyme (lysophospholipase D) that catalyzes the hydrolysis of lysophosphatidyl choline to lysophosphatidic acid (LPA). The ATX-LPA axis is a well-known pathological mediator of liver fibrosis, metastasis in cancer, pulmonary fibrosis, atherosclerosis, and neurodegenerative diseases. Also, it is believed that LPA may cause vascular permeability. In ischemic stroke, vascular permeability leading to hemorrhagic transformation is a major limitation for therapies and an obstacle to stroke management. So, in this study, we generated an endothelial-specific ATX deletion in mice (ERT2 ATX-/-) to observe stroke outcomes in a mouse stroke model to analyze the role of endothelial ATX. The AR2 probe and Evans Blue staining were used to perform the ATX activity and vascular permeability assays, respectively. Laser speckle imaging was used to observe the cerebral blood flow following stroke. In this study, we observed that stroke outcomes were alleviated with endothelial deletion of ATX. Permeability and infarct volume was reduced in ERT2 ATX-/- mice compared to ischemia-reperfusion (I/R) only mice. In addition, cerebral blood flow was retained in ERT2 ATX-/- compared to I/R mice. The outcomes in the stroke model are alleviated due to limited LPA concentration, reduced ATX concentration, and ATX activity in ERT2 ATX-/- mice. In this study, we observed that ATX produced by the endothelium could be a major factor responsible for increases in permeability and infarcts, and adverse effects on the cerebral blood flow during cerebral ischemic reperfusion. LPA produced specifically by endothelial cells in the vasculature can disrupt the BBB leading ultimately to neuronal loss and glial activation. With the deletion of ATX from the endothelium, the microvasculature might be more resilient due to reduced LPA. We found evidence that the functional outcomes of ischemic stroke were alleviated with ATX deletion. Therefore, endothelial ATX can be targeted to make better and more effective therapies for stroke management. his research was supported by Louisiana State University Health Sciences-Shreveport Intramural Grant 110101074A to SM; National Institutes of Health grants HL141998 and HL141998-01S1 to SM; grants AA025744, AA026708, and AA025744-02S1 to MP; grants HL122354 and HL145753 to MSB; P20GM12130 to Dr. Christopher Kevil. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Characterization of Ghrelin O-acyltransferase mRNA in channel catfish
Authors: Johnson Emily , Miller Sarah , Kobayashi Yass 
Published: May 2023

Food intake is regulated by the reaction between hypothalamic neurotransmitters and peripheral signals. Ghrelin, known as a hunger hormone, stimulates food intake. Ghrelin O-acyltransferase (GOAT) catalyzes the acylation of medium-chain fatty acids to ghrelin to modify ghrelin activity. GOAT is found in all vertebrates, including fish, and is critical for modifying the activity of ghrelin. We hypothesized that GOAT is critical for regulating food intake because it modifies the activity of ghrelin in channel catfish. However, very little is known about GOAT in channel catfish, including the tissue distribution of its mRNA. We identified the nucleotide sequence that corresponds to the GOAT mRNA in GenBank. The sequencing alignment analysis showed that the sequence similarity between channel catfish GOAT mRNA and those of other fish species was high (>65%) in the region that corresponded to the open reading frame of the channel catfish GOAT mRNA. Examination of the tissue distribution of GOAT mRNA, including the brain, liver, muscle, kidneys, spleen, heart, and small and large intestines, revealed that GOAT mRNA expression was detectable in the brain, small intestine, and muscles. We are currently verifying the results of tissue distribution analysis using quantitative real-time PCR. We are also examining the relationship between changes in food intake and the expression of GOAT mRNA in the brain and muscle using real-time PCR. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Dapagliflozin Attenuates Sodium Chloride Cotransporter (NCC) Protein Expression while Improving Urine Osmolality and Decreasing Blood Pressure in Hypertensive Diabetic db/db Mice
Authors: Gholam Mohammed , Alli Abdel 
Published: May 2023

The prevalence of hypertension in diabetic patients varies depending on age, gender, ethnicity, body mass index (BMI), glycemic management history, and the presence of kidney disease. In addition, hypertension is a major contributor to the development of atherosclerotic cardiovascular disease (ASCV), heart failure, and microvascular consequences. In the kidney, NCC is expressed in cells of the distal convoluted tubules. About 10% of the filtered load of sodium is reabsorbed by renal NCC. Recently, dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, was introduced as an effective class of glucose-lowering agents for the treatment of type 2 diabetes. We hypothesize that dapagliflozin mitigates blood pressure by restoring normal renal functions. Twelve week-old male db/db mice with a blood glucose of more than 300 mg/dl were salt-loaded (4% NaCl) for 10 days to induce hypertension. The mice were subjected to metabolic cage studies for 24-hour urine collections to measure urinary electrolytes. Blood pressure was measured by the tail-cuff method to evaluate the effect of dapagliflozin (n=8), or vehicle (n=8) given by oral gavage (1 mg/kg of body weight per day for 2 weeks). Total NCC protein expression was reduced in kidney cortex membrane fractions, while there was increased urinary sodium levels, from dapagliflozin treated mice compared to vehicle treated mice. Urine osmolality was improved in the dapagliflozin treated group compared to the vehicle treated. Additionally, blood glucose, systolic blood pressure, and urinary potassium levels were reduced in the dapagliflozin treated group. Taken together, these results suggest blood pressure is normalized after dapagliflozin treatment in a mechanism involving reduced renal NCC and increased excretion of sodium. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Dietary cannabidiol activates PKA/ERK/AMPK signaling and attenuates chronic inflammation and leaky gut in DSS-induced colitis mice
Authors: Sun Qi , Iniguez Alejandro , Tian Qiyu , Du Min , Zhu Meijun 
Published: May 2023

Study objectives: This study is aimed to examine the impact of dietary cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, on dextran sulfate sodium (DSS)-induced experimental colitis in mice. Hypothesis: Dietary CBD exerts beneficial effects against DSS-induced experimental colitis in mice colon through protecting barrier function and suppressing inflammatory response. Methodology: Eight-week-old C57BL/6J female mice were fed a standard rodent diet supplemented with or without CBD (200 milligrams per kilogram) for 5 weeks. In the 4th week of dietary treatments, mice were subjected to 2.5% DSS induction for 7 days followed by 7 days of recovery to induce colitis. The disease activity index was monitored daily during the induction and recovery periods. After recovery, mice were euthanized, and colon tissues were collected for analysis. Data CBD supplementation reduced body weight loss, gross bleeding, fecal consistency score, and disease activity index. In addition, CBD supplementation protected the colonic structure and ameliorated mucosal damage and macrophage infiltration in the colonic tissue, which is associated with activated cAMP-protein kinase A (PKA), extracellular signal-regulated kinase (ERK) 1/2 and AMP-activated protein kinase (AMPK) signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and pro-inflammatory cytokine secretion. Consistently, CBD feeding decreased the contents of pore-forming tight junction protein claudin-2 and myosin light chain kinase in DSS-treated mice. Summary of results Dietary CBD improves DSS-induced colitis and activates PKA and AMPK signaling pathways to suppress inflammation and enhance gut barrier function. Conclusions: Dietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management. Funding Sources: Washington State University Dedicated Marijuana Account (DMAc) grant and Agricultural Research Center Emerging Research Issues Competitive Grant. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Dietary purple potato mediates intestinal oxidative phosphorylation and mitochondrial unfolded protein response in DSS-induced colitis mice
Authors: Sun Qi , Bibi Shima , Xue Yansong , Du Min , Zhu Meijun 
Published: May 2023

Study objectives: This study is to evaluate the beneficial role of purple potato (PP) supplementation against colitis symptom on dextran sulfate sodium (DSS)-induced murine colon colitis and further explore the underlying mechanisms. Hypothesis: Dietary PP enhances intestinal mitochondrial biogenesis and protect against DSS-induced colitis. Methodology: Six-week-old C57BL/6J male mice were randomized into 4 groups feeding a standard rodent diet supplemented with or without 10% PP powder for 7 weeks. At the 5th week of dietary treatments, mice in each group were further divided into two groups and received with or without 2.5% DSS induction for 7 days followed by 7 days of recovery, when mice were euthanized for tissue collection. Data PP supplementation ameliorated the disease activity index in DSS-treated mice and reversed the colonic structure loss, mucosal damage, macrophage infiltration, and proinflammatory cytokine secretion induced by DSS in the colonic tissue. Dietary PP restored the protein contents of tight junction proteins and caudal-type homeobox 2 (CDX2) in DSS-treated mice. Furthermore, dietary PP activated AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α signaling pathways as well as enhanced mitochondrial oxidative phosphorylation and mitochondrial proteostasis. Summary of results: Dietary PP ameliorated DSS-induced colitis and enhanced gut structures and barrier function which were associated with improved mitochondrial function. Conclusions: Data collectively showed PP supplementation had protective effects against colitis and is a promising dietary strategy for colitis management. Funding Sources: United States Department of Agriculture-National Institute of Food and Agriculture (USDA-NIFA) (2018-67017-27517) and Washington State University Agricultural Research Center Emerging Research Issues Competitive Grant. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.