bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Bolus Dose of PTH 1‐84 Elicited Sustained Elevations in Intramedullary Pressure in Rat Femora
Authors: NOH Sunggi 
Published: June 2021

BACKGROUNDPrevious studies demonstrated that chronic increases and decreases in bone intramedullary pressure (IMP) augments and reduces bone mass, respectively. Parathyroid hormone (PTH) plays a central role in the regulation of bone remodeling and augments bone mass. We previously reported augmented vasodilation of the femoral principal nutrient artery (PNA) to cumulative doses of PTH 1‐84, PTH 1‐34 and PTHrP 1‐34. In addition, bone perfusion is augmented following a bolus dose of PTH. Since PTH increases vasodilation and blood flow, we sought to assess its effects on bone IMP. The purpose of the study was to sequentially examine IMP in rat femora following PTH administration.METHODSMale Wistar rats (3–5 months) were randomly divided into the following groups: Control (CON, n = 7), PTH120 (n = 7), PTH150 (n = 7), and PTH330 (n = 7). Rats were anesthetized (2% isoflurane to O2 balance) and right femoral shafts were catheterized. At this time, the PTH groups received PTH 1‐84 (100 μg/kg, s.c.) and CON received PBS (100 μl, s.c.). The rats were sacrificed 120, 150 and 330 minutes following surgery. Just prior to sacrifice, the catheter was connected to a pressure transducer and in vivo IMP (mmHg) was recorded (PowerLab, AD Instruments) in the conscious rodents. The last 10 minutes of data were averaged and reported. Alpha level was set a priori at p<0.05 and One‐way ANOVA and Student Newman‐Keuls post hoc were performed to determine group differences.RESULTSBody mass did not differ among groups: CON, 478 ± 8 g; PTH120 474 ± 9 g; PTH150, 458 ± 6 g; PTH330, 488 ± 4 g. IMP was augmented (p<0.05) at PTH120 (33 ± 3 mmHg), PTH150 (35 ± 6 mmHg), PTH330 (41 ± 4 mmHg) vs. CON (20 ± 3 mmHg). IMP did not differ among the PTH groups.CONCLUSIONPTH increased bone IMP and sustained this response for up to 5 1/2 hours (i.e., 330 min) following administration. This increase in pressure corresponds with reports of enhanced vasodilation and bone perfusion following bolus administration of PTH. Given the bone altering effects of chronic IMP modulation, enhanced IMP with PTH administration may represent another mechanism by which it induces bone anabolism.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chemerin decreases vascular reactivity to contractile stimuli in resistance vessels from Sprague Dawley rats fed a high fat diet for 1 month
Authors: Klee Nicole , McKinzie Jaine , Arishe Olufunke , Priviero Fernanda , Webb Clinton 
Published: June 2021

Obesity and cardiovascular disease (CVD) are comorbid with a common underlying pathophysiology. The adipokine chemerin positively correlates with both obesity and CVD and has been proposed as the link between fat and arterial contraction. Chemerin has been shown to augment vascular reactivity to contractile stimuli; however, the effects of a high fat diet (HFD) on chemerin vascular reactivity are currently unknown. We hypothesize that animals fed a HFD will have augmented vascular responses to chemerin compared to regular diet fed controls. We fed 13–15 week old Sprague Dawley rats with a HFD (45% kcal) or regular diet for 1 month [body weight (g), regular diet: 410 ± 4.573 vs. HFD: 443 ± 12.77; p<0.05). Vascular function was performed on isolated mesenteric resistance arteries (MRA), pudendal arteries, and aorta using wire and pin myographs. Vascular reactivity in response to a chemerin concentration response curve (10−9 M–10−5 M) was not significantly different between regular and HFD fed animals in any vascular bed we measured. Aortic vascular reactivity to phenylephrine (PE) in both regular and HFD was significantly augmented after 1 hour chemerin incubation (0.5 ng/mL and 5 ng/mL). However, after 1 month of HFD reactivity to PE was significantly decreased in resistance arteries after 1 hour incubation with chemerin (5 ng/mL) compared to vehicle [Force (mN) (PE 10−9 M–10−5 M), vehicle vs. chemerin; interaction pudendal p<0.05, MRA p<0.05]. This response was absent in the regular diet fed group [Force (mN) (PE 10−9 M–10−5 M), vehicle vs. chemerin; interaction pudendal p = 0.9497, MRA p = 0.9834].Our data indicate that in regular diet fed male Sprague Dawley rats, chemerin augments vascular reactivity in conductance but not resistance vessels. After 1 month of a HFD, the effects of chemerin in resistance vessels decreased but did not change the augmented vascular reactivity seen with regular diet in conductance vessels. Therefore, our hypothesis that chemerin would augment vascular reactivity in animals fed a HFD was not supported by our results. It is important to note that longer term studies are needed.Support or Funding InformationNIH PO1 HL‐134604This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mouse Genetic Background influences Endothelial Function along the Mouse Vascular Tree
Authors: Holly Dylan Stone , Kim Hyoseon , Shin Song Yi , Dezell Hannah , Woodman Christopher R , Massett Michael P 
Published: June 2021

The endothelium is critical for maintaining vascular integrity and protecting against cardiovascular disease. Endothelial dysfunction is associated with a host of disease states including cardiovascular disease, diabetes, chronic kidney disease, and Alzheimer's disease. However, it is unclear whether endothelial function or dysfunction varies throughout the vasculature. In addition, accumulating evidence suggests that endothelial function, and more generally vasomotor function, is genetically regulated. The purpose of this study was to determine the influence of genetic background on vasomotor function in blood vessels of differing size. Vasomotor function was measured in aorta (thoracic (TA), and abdominal (AA)) and conduit arteries (carotid artery (CA) and femoral artery (FA)) from two inbred strains (NZW/LacJ (NZW) and C57BL/6J (B6)) of mice. Arteries were dissected, cut into 2 mm segments, and mounted in a wire myograph system. Increasing concentrations of phenylephrine (PE, 1×10−9 – 1×10−5M) were used to measure contractile responses, while increasing concentrations of the endothelium‐dependent vasodilator acetylcholine (ACh, 1×10−9 – 1×10−5M) and endothelium‐independent vasodilator sodium nitroprusside (SNP, 1×10−9 – 1×10−5M) were used to assess relaxation responses. Contractile responses to PE were not significantly different between strains across all vessels. Endothelium‐dependent relaxation to ACh was significantly impaired in TA (P = .0001), AA (P = .0019), and FA (P = .0002) from NZW as compared to B6, while CA relaxation responses were not statistically different between groups. Sensitivity to ACh as determined by IC50 was impaired in NZW TA (P = .0006), AA (P = .0005), CA (P = .001), and FA (P = .0003). Relaxation responses to the endothelium‐independent vasodilator SNP were not statistically different in the AA, CA and FA, while TA relaxation to SNP was statistically lower in B6 TA compared to NZW (P = .02). Sensitivity to SNP was not statistically different between groups for TA, CA, and FA but NZW AA showed a greater sensitivity to SNP than did B6 (P = .0304). These findings indicate a strong influence of genetic background on vasomotor function and could be important in understanding the implications that genetics have on vascular response to vasoactive agents.Support or Funding InformationThis work was supported by a Texas A&M Triads for Transformation grant (Michael Massett, Christopher Woodman), a Texas A&M Merit Fellowship (Dylan Holly), and a Texas A&M College of Education Strategic Research Award (Song Yi Shin).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
MicroRNA Profiling in Coronary Endothelial Cells in Type 2 Diabetic Mice
Authors: Zhang Qian , Tsuji‐Hosokawa Atsumi , Watanabe Makiko , Makino Ayako 
Published: June 2021

Coronary endothelial dysfunction is a major cause of cardiac ischemia and it is commonly seen in patients with diabetes. MicroRNAs (miRNAs) are small noncoding RNAs that modulate the expression of multiple mRNAs. There is increasing evidence showing that the change in miRNA expression is implicated in the development and/or progression of cardiovascular diseases. However, the pathological role of miRNAs in coronary endothelial dysfunction in type 2 diabetes (T2D) is still unknown. MicroRNA array was used to profile the expression level of miRNAs in coronary endothelial cells (ECs) isolated from control and T2D mice. Real time PCR analysis was performed to confirm the miRNA array results. Among 491 murine miRNAs tested, 64 up‐regulated and 20 down‐regulated miRNAs were identified and seven miRNAs (miR106b, 210, 221, 222, 342‐5p, 378, 705, fold change>1.25) were selected to confirm the data using real‐time PCR. Real time PCR data revealed that miR378 expression was significantly higher and miR210 and miR342‐5p expression levels were significantly lower in diabetic ECs than in control ECs. To identify the target genes of miR378 and 342‐5p, we transfected miR378 mimic or miRNA342‐5p inhibitor in mouse coronary ECs. We chose 91 genes that are highly expressed in ECs and play crucial roles in endothelial functions, including a) endothelium‐derived relaxing factors and their regulators; b) modifiers of cytosolic, mitochondrial, and endoplasmic Ca2+ concentration; and c) regulators of EC proliferation/migration/apoptosis. The real‐time PCR data showed that miR378 mimic overexpression altered mRNA levels of 11 genes and miR342‐5p inhibitor in 5 genes. Among those genes, Vegfb, Atp3a3, Stim2 were decreased in coronary ECs transfected with miRNA mimic or inhibitor and in coronary ECs in T2D mice compared to their controls. These data suggest that miR378 and/or miR342‐5p are a potential target to restore coronary endothelial dysfunction in diabetes.Support or Funding InformationThis work was supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL142214 to A. Makino).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lower baroreflex sensitivity during muscle metaboreflex activation in children and adolescents with the Fontan circulation and single ventricle physiology
Authors: Boyes Natasha G , Iqbal Ramlah M , Fusnik Stephanie , Lahti Dana S , Erlandson Marta C , Wright Kristi D , Kakadekar Ashok , Bradley Timothy J , Pharis Scott , Pockett Charissa , Olver T Dylan , Tomczak Corey R 
Published: June 2021

Individuals with the Fontan circulation and single ventricle physiology have elevated sympathetic nerve activity at rest and during muscle metaboreflex activation that is consistent with autonomic dysfunction. Adults with the Fontan circulation also show reduced baroreflex sensitivity (BRS); however, there is limited understanding of BRS in children or adolescents with the Fontan circulation. In healthy adults, BRS decreases with increased sympathetic nerve activity during isometric handgrip exercise, but not during isolated muscle metaboreflex activation. The effect of handgrip exercise and muscle metaboreflex activation on BRS in children and adolescents with the Fontan circulation is currently unknown.PURPOSEWe tested the hypothesis that BRS is lower at rest and less responsive during handgrip exercise and post‐exercise circulatory occlusion (PECO) in children/adolescents with the Fontan circulation compared to healthy controls.METHODSEight children/adolescents with the Fontan circulation (12 ± 2 yrs; 3 males) and 8 healthy controls (13 ± 4 yrs; 5 males) were studied. Continuous heart rate (ECG) and non‐invasive blood pressure (Finometer® MIDI) were recorded during 3‐min of resting baseline, 2‐min of isometric handgrip exercise at 30% of maximal voluntary contraction, and 3‐min of PECO. Continuous heart rate, systolic blood pressure, and diastolic blood pressure signals were analyzed using the BRS Analysis software (Nevrokard, Slovenia, 2018) to yield average BRS values during rest, handgrip, and PECO for each group. Differences between groups and across conditions were assessed using two‐way repeated measures (2 × 3, group × condition) ANOVA. P<0.05 was considered significant.RESULTSThere was a significant group × condition interaction for BRS (P<0.001). BRS was lower in children/adolescents with the Fontan circulation vs. healthy controls at rest (13 ± 8 vs. 38 ± 10 ms/mmHg; P<0.001) and during PECO (18 ± 17 vs. 37 ± 18 ms/mmHg; P=0.044), but not during handgrip (13 ± 10 vs. 14 ± 6 ms/mmHg; P=0.843). BRS in children/adolescents with the Fontan circulation did not change across conditions (P=0.188).CONCLUSIONOur findings suggest that BRS is lower at rest and has a blunted response during sympatho‐excitation in children/adolescents with the Fontan circulation compared to healthy controls. Collectively, our findings indicate potential autonomic dysfunction in children/adolescents with the Fontan circulation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Determination of the Role of LOX‐1 during Escherichia coli Pneumonia
Authors: Molina William , Korkmaz Filiz , Symer Elyse , Jones Matthew , Mizgerd Joseph , Traber Katrina , Quinton Lee 
Published: June 2021

Pneumonia is primarily caused by infection from bacteria, virus, and/or fungi and results in an acute lower respiratory tract inflammation. It is responsible for severe morbidity and mortality worldwide. Pneumonia is the foremost cause of children's hospitalizations in the United States and accounts for more than 935,000 deaths globally. In mice with severe bacterial pneumonia it is known that the pathophysiology of pneumonia is due to the overt activation and recruitment of host innate immune cells. Data generated in our lab has shown that there is an induction of the OLR1 gene that expresses lectin‐like oxidized low‐density lipoprotein receptor 1 (LOX‐1) in the lungs of mice during pneumonia. LOX‐1 is a receptor that is expressed in many cells, including host innate immune cells and it is commonly associated with atherosclerosis and inflammation. Herein, we aim to understand the role LOX‐1 plays during Gram‐negative bacterial pneumonia. Our recent results indicate that local neutralization of LOX‐1 within the lungs during pneumonia caused a significant increase in total tissue injury and inflammatory cytokines, indicating that LOX‐1 may have a protective effect.To determine the effect of LOX‐1 inhibition systemically, an intraperitoneal injection with 10 μg of anti‐LOX‐1 antibody was administered to neutralize LOX‐1 in C57BL/6J mice that were subsequently infected with Escherichia coli. Mice were euthanized 24 hours after infection and bronchoalveolar lavage fluid (BALF) samples were collected. In an ex vivo system, mouse lung epithelial (MLE‐12) cells were similarly treated with anti‐LOX‐1 antibody to observe the effect of neutralizing LOX‐1 on epithelial cell death. BALF from infected and uninfected mice was also added in the ex vivo model to more accurately recreate the conditions of the alveolar space. Total protein from MLE‐12 cells was then collected 24 hours after stimulation for analysis and characterization.Overall, the systemic neutralization of LOX‐1 in C57BL/6J mice during bacterial pneumonia did not significantly affect leukocyte recruitment or lung injury. In addition, ex vivo LOX‐1 neutralization in MLE‐12 cells did not affect apoptosis as measured by cleaved caspase‐3 on a western blot. In contrast with local inhibition of LOX‐1 in the lungs, systemic inhibition of LOX‐1 did not significantly limit tissue injury in mice with pneumonia. Blockade of LOX‐1 in ex vivo model did not remarkably affect epithelial cell death or apoptosis. Further studies involving measurement of resistance and resilience of lung tissue are underway and will more completely characterize the role of LOX‐1 during pneumonia.Support or Funding InformationNIH grants R01‐HL111449, R01‐GM120060, and T32‐HL007035.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in Systemic and Renal Tissue Urea Concentrations
Authors: Boesen Erika Ingrid , Wang‐France Jun , Rahman Shamma Shakila 
Published: June 2021

Inner medullary urea accumulation is believed to play a key role in determining urinary concentrating ability. We had previously studied the effects of different levels of dietary protein concentration on renal excretory function in mice as a test of renal urea handling. Unexpectedly, we observed an increase of urine flow in male but not female mice when switched to a low protein diet (6% protein). To further investigate this phenomenon, we fed diets containing either a low (6%) or normal (20%) protein content to male and female mice for 7 days (n=7–10/group), followed by collection of plasma and renal tissue for measurement of osmolarity and urea concentration. Plasma osmolarity was significantly lower in female compared with male mice irrespective of diet (PSex< 0.05), and both sexes had significantly lower plasma osmolarities on 6% compared with 20% protein diets (by ~5 mOsmol/kg. H2O; PDiet<0.001). Dietary protein levels had a significant effect on plasma urea concentration irrespective of sex, with urea concentrations being lower on 6% compared with 20% protein diet (PDiet< 0.0001). Plasma urea levels were also significantly lower in female compared to male mice independent of diet (PSex<0.001). The effect of dietary protein intake varied by sex (PSex*Diet<0.01), with plasma urea concentration significantly higher in male compared to female on 20% protein diet (P<0.05 by post‐hoc test; male 9.7 ± 0.3 mM, female 6.8 ± 0.5 mM) but not on 6% protein diet (P>0.05; male 4.9 ± 0.3 mM, female 4.5 ± 0.1 mM). Inner medullary tissue osmolarity was significantly lower on 6% compared to 20% protein diet, independent of sex (PDiet<0.01), but there was no significant sex difference (PSex=0.8) or difference in the way the sexes responded to diet (PSex*Diet=0.8). Dietary protein levels also had a significant effect on inner medullary urea concentration, being lower on 6% compared to 20% protein diet in both male and female mice (PDiet<0.01). Further, there was a sex difference in inner medullary tissue urea concentration, with male mice showing lower urea concentrations compared to female mice, independent of level of dietary protein content (PSex=0.05). There were no significant effects of sex or diet on outer medullary or renal cortical tissue osmolarity, or on outer medullary tissue urea concentration. Renal cortical tissue urea concentration was significantly higher in female compared to male mice, independently of diet (PSex<0.01), but there no significant effect of the level of dietary protein content (PDiet=0.07). Together, our data indicate that there are sex differences in circulating and renal tissue urea concentrations, which we speculate may contribute to sex differences in the effect of dietary protein intake on urinary concentrating ability.Support or Funding InformationAmerican Heart Association 17GRNT33661008This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Physical and Metabolic Characteristics of p62 Knockout Mouse: A New Animal Model of Obesity/Insulin Resistance
Authors: Kim Do‐Houn , Salazar Gloria , Hwang Hyun‐Seok , Klemp Alex , Yeh Ming‐Chia , Worts Phillip R. , Panton Lynn B. , Arjmandi Bahram H. , Grant Samuel C. , Kim Jeong‐Su 
Published: June 2021

ObjectivesThe p62 deficient mouse exhibits a similar but unique phenotype of obesity compared to other diet‐induced or genetically modified obesity models. Our study aimed to further characterize physical and metabolic properties of p62 knockout mice.MethodsMale C57BL/6 p62 knockout (p62−/−, 14 weeks old, n=9) and sex‐/age‐matched C57BL/6 wildtype control mice (CON, n=9) were studied. All mice were raised separately with access to standard rodent chow and water ad libitum. Food intake and body weight changes were monitored biweekly for 20 weeks. At 24 and 34 weeks of age, all mice went through in vivo assessments of body composition (dual X‐ray absorptiometry), neuromuscular function (grip strength and inclined plane test), and oral glucose tolerance tests (OGTT). Additionally, at 34 weeks of age, hindlimb muscles (i.e., gastrocnemius, soleus, and plantaris) and the spleen were extracted and weighed. The isolated muscles were analyzed for myofiber cross‐sectional area (CSA) and expression levels of regulatory proteins for muscle growth (i.e., mTOR, AKT, atrogin1, and MuRF1), insulin signaling [i.e., insulin receptor β (IR‐β) and GLUT4], and proinflammation (i.e., TNF‐α).Resultsp62−/− demonstrated greater daily food intake and weight gain leading to obesity at 22 weeks of age compared to CON (p<0.05). At 24 weeks of age, p62−/− displayed greater total body mass and fat mass (p<0.05), and these changes were even greater at 34 weeks of age. p62−/− showed higher fasting blood glucose levels and diminished blood glucose clearance leading to greater postprandial blood glucose (p<0.05). No significant differences in grip strength and sensorimotor function were observed in p62−/− compared to CON. In vitro analysis revealed no group difference in muscle wet weights; however, spleen weights were greater in p62−/− than CON. p62−/− exhibited greater myofiber CSA than CON (p<0.05). There was a suppressed expression ratio of phosphorylated AKT to total AKT in the gastrocnemius of p62−/− (p<0.05).ConclusionYoung adult p62−/− mice developed obesity accompanied by insulin resistance and systemic inflammation, which was attributable, at least in part, to increased food intake. However, it is noteworthy that p62−/− mice exhibited greater myofiber CSA while maintaining skeletal muscle mass and function during progression of obesity.Support or Funding InformationJiwon Co. LtdThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.