bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Leg Fidgeting During Sitting on Glycemic Control in Obese Subjects – A Pilot Study
Authors: Pettit‐Mee Ryan J. , Ready Sean T. , Liu Ying , Padilla Jaume , Kanaley Jill A. 
Published: June 2021

BackgroundProlonged sitting is associated with glycemic excursions, which are likely more pronounced within individuals with risk factors for cardiovascular disease or type 2 diabetes. Strategies to minimize inactivity during sitting are needed to offset its consequences. While chair‐based fidgeting can increase energy expenditure above basal resting metabolic rate, the effect of this minimal amount of physical activity on glycemic control during prolonged sitting has not been investigated. Therefore, the purpose of this ongoing clinical trial is to assess the effect of leg fidgeting during prolonged sitting on glycemic control in obese individuals.DesignFour obese women (43 ± 15 years; BMI = 35 ± 5.9 kg/m2) participated in a randomized cross‐over design study involving two experimental visits. Overnight‐fasted subjects sat in an office chair, ingested a 75 g glucose beverage, and then either refrained from leg movement or performed continuously repeated bouts of bilateral leg fidgeting (2.5 mins of leg fidgeting followed by 2.5 mins of rest) for the next three‐hours. Intravenous blood glucose sampling occurred throughout. Accelerometer data from one leg and popliteal artery blood flow measurements were recorded during the sitting period.ResultsLeg fidgeting resulted in increased accelerometer counts compared to no leg fidgeting (~16‐fold) as designed. In conjunction, leg fidgeting increased popliteal artery blood flow (P<0.05). Each bout of leg fidgeting resulted in elevated blood flow that normalized after 36 seconds (P<0.05) following leg fidgeting cessation. Despite these indicators of increased leg movement and metabolic demand, blood glucose total and incremental area under the curves were not significantly lowered with bilateral leg fidgeting. Blood Glucose concentrations at any time‐point were not different between conditions.ConclusionsLeg fidgeting is not a sufficient stimulus to improve blood glucose concentrations in obese individuals during prolonged periods of physical inactivity, i.e. prolonged sitting. Further investigation is needed to assess more effective physical activity modalities and minimum thresholds of physical activity during sitting to improve blood glucose levels.Support or Funding InformationInstitutional support.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Murine Live Bladder Tissue Model to Study the Microvasculature Properties and Function In Situ
Authors: de Sousa Loreto Aresta Branco Mafalda , Taylor Kirsti D. , Bowen Jenna L. , Peppiatt‐Wildman Claire M. , Wildman Scott S.P. 
Published: June 2021

Regulation of microvascular blood flow in the bladder has historically been associated with regulation by pre‐capillary arterioles and more recently to post‐capillary venules. Although pericytes are known to regulate capillary vessel diameter in various capillary beds (e.g. brain, retina, heart and kidney), their role in regulating bladder capillary diameter remains controversial.We have developed a mouse full‐thickness live bladder tissue model in which the microvasculature of the mucosa can be visualised in situ, enabling the regulation of suburothelial capillary diameter to be investigated. Bladder tissue viability was first investigated by fluorescence imaging of tissue labelled with Hoechst and propidium iodide to determine the live to dead cell ratio. Data indicated that tissue was viable in situ for up to 5 hours (>60%; P>0.05; n = 3 per time point). Real time DIC images of live tissue sections were collected for all experiments in which live tissue was exposed to vasoactive agents to investigate the pericyte‐mediated regulation of capillary diameter. Images were analysed off line and vessel diameter was measured at both pericyte and non‐pericyte sites along a capillary for each experiment. Angiotensin II (100 nM) and endothelin I (1 nM) evoked a pericyte‐mediated vasoconstriction of suburothelial capillaries at pericyte sites (13.3 ± 5.8%, 22.0 ± 9.7%) that was significantly greater (p<0.05, n = 6 per drug) than that measured at non‐pericyte sites (3.2 ± 2.7%, 6.0 ± 3.4%). Prostaglandin E2 (30 μM) evoked a pericyte‐mediated dilation of capillaries (12.1 ± 2.6%) that was significantly greater than that measured at non‐pericyte sites (2.3 ± 2.3%, p = 0.03, n = 3).In this study we therefore demonstrate that suburothelial capillary pericytes act to regulate capillary diameter in response to agents previously reported to regulate capillary beds of other organs. This indicates that in addition to smooth muscle‐mediated regulation of upstream vessels in the bladder, spatial regulation of capillary diameter downstream of these vessels also occurs in the bladder.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Microvascular Blood Flow Response to Hyperinsulinemia in Type 2 Diabetic Rats
Authors: Shogan Hamza , Russell McEvoy Gaylene M , Fraser Graham M 
Published: June 2021

ObjectiveChronic hyperglycemia is a defining feature of type 2 diabetes (T2D) that has been implicated in impaired microvascular structure and function. We aim to quantify the effect of hyperglycemia on local hemodynamic changes and spatial redistribution of blood flow in skeletal muscle capillary networks in response to hyperinsulinemia in an animal model of T2D.MethodsFour 12‐week‐old Zucker Diabetic Fatty (ZDF) rats (2 lean, 2 obese) were fed a high fat diet (Purina 5008), acclimatized in animal quarters, and randomly selected on the day of experiment. Animals were anesthetized with sodium pentobarbital; cannulas were placed into the left common carotid and right jugular vein for systemic monitoring, anaesthetic administration and fluid resuscitation; animals were then tracheotomized and mechanically ventilated. Animals were maintained at 37□for the duration of the experiment and data collection. The right Extensor Digitorum Longus (EDL), a muscle of the lower‐hind limb, was isolated, and the distal tendon was cut to reflect the belly of the muscle over the objective of an Olympus IX‐73 microscope. Intravital videos of the microcirculation were recorded in 4–6 microscopic fields at multiple focal planes to capture blood flow in discrete capillary networks during baseline conditions. Euglycemia was achieved through intravenous infusion of insulin (2000 mU/kg/hr) and glucose (500 mg/kg/hr) until 3 stable blood glucose readings between 5 – 7 mM were made. Euglycemia was maintained while recordings were repeated in the same microscopic fields acquired during baseline.ResultsResting blood glucose concentrations were 6.9 ± 0.4 mM for lean and 17.9 ± 1.2 mM for obese animals. At euglycemia, lean animals were brought to blood glucose levels of 6.3 ± 0.1 mM and obese to 6.2 ± 0.9 mM; mean glucose infusion rates were 28.9 ± 2.9 mg/kg/min for lean and 1.8 ± 2.1 mg/kg/min for obese animals. At baseline, mean capillary red blood cell (RBC) velocities were 233.0 ± 28.9 vs. 263.1 ± 24.2, hematocrits were 19.9 ± 4.3 vs. 32.9 ± 4.8, and RBC supply rates were 15.9 ± 1.3 vs. 21.9 ± 1.4 in lean and obese animals respectively (n = 525 capillaries). During hyperglycemia lean animals showed an 33% increase in RBC supply rate while obese animals showed a 25% decrease (n = 357 capillaries).ConclusionHyperglycemia in control animals caused a marked increase in RBC supply rate in skeletal muscle tissue which may be an adaptive mechanism to enhance glucose uptake. This capillary flow response appears to be impaired in obese ZDF animals that share many characteristics with human T2D.Support or Funding InformationThis project was supported by a Medical Research Fund grant to GM Fraser from the Faculty of Medicine, Memorial University of Newfoundland.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Towards a Multi‐Scale Model of Ventilation‐Perfusion Matching
Authors: Marquis Andrew D , Beard Daniel A , Pinsky David J 
Published: June 2021

Ventilation‐Perfusion (V/Q) matching is a critical determinant of efficient gas exchange in the pulmonary circulation. The regulatory mechanisms that control V/Q matching under normal and pathological scenarios are incompletely understood. In this study we present the derivation and validation of a multi‐scale computer model of hemodynamics and gas exchange accounting for the fractal‐like pattern of pulmonary vascular branching, mechanical coupling of blood‐tissue interactions, gas exchange, hemoglobin biochemistry, and vasoregulatory mechanisms. By simulating the regional distribution of V/Q ratios, this model serves as an in‐silico platform to test and refine hypotheses regarding the contributions of vasoregulatory mechanisms to regional perfusion and V/Q matching in the lung. Figure 1 depicts the various model “blocks” and how they are interconnected. The complete model is formulated as an algebraically constrained system of ordinary and partial differential equations and is parameterized to represent function in an adult Sprague Dawley rat. Block (A) illustrates the whole‐lung vascular network model. The network geometry is generated by a space‐filling algorithm and is validated by comparing anatomical predications (length, radius, and connectivity) to morphometric data (from existing literature). Block (B) shows how the mechanics of each vessel segment is represented as a lumped system. Mechanics are validated by comparing model predictions to macro‐scale pressure‐flow relationships and pulmonary artery pressure waveforms (from existing literature and our own in vivo studies). Block (C) depicts a representative gas exchange unit. Block (D) portrays oxygen‐sensitive vasoregulatory mechanisms that have been implicated in the maintenance of pulmonary vasomotor tone. Model simulations illustrate that perfusion heterogeneity is governed by the geometry of the vascular tree, and local interaction between alveolar and vascular pressures. Moreover, conducted vascular responses (hypoxic pulmonary vasoconstriction, and the hypoxia‐mediated/mechanically‐transduced release of ATP from red blood cells) modulate the redistribution of blood flow in response to pathological insults such as a pulmonary embolism. Taken together, our results suggest that more homogenous blood flow distributions increase the bulk oxygen content entering the systemic circulation.Support or Funding InformationNIH/NINDS R01 NS087147NIH/NHLBI R01 HL127151This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
High Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice
Authors: Peri‐Okonny Poghni Allen , Baskin Kedryn K. , Iwamoto Gary , Mitchell Jere H. , Smith Scott A. , Kim Han Kyul Allen , Szweda Luke I , Bassel‐Duby Rhonda , Fujikawa Teppei , Castro Carlos M. , Richardson James , Shelton John M , Ayers Colby , Berry Jarett D. , Malladi Venkat S. , Hu Ming‐Chang , Moe Orson W. , Scherer Phillip E , Vongpatanasin Wanpen 
Published: June 2021

BackgroundInorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown if dietary Pi excess contributes to exercise intolerance and physical inactivity.MethodsWe used multivariable linear regression (adjusted for age, sex, race, body mass index, systolic blood pressure, eGFR, fasting plasma glucose, and HDL cholesterol) to assess the relationship between serum Pi and actigraphy‐determined physical activity level as well as left ventricular function by cardiac magnetic resonance imaging in the Dallas Heart Study‐2 (DHS) participants. To determine direct effects of dietary Pi on exercise capacity, we measured oxygen uptake, serum non‐esterified fatty acid (NEFA) and glucose during exercise treadmill test and compared between C57/BL6 mice fed either a high Pi (2%) or normal Pi (0.6%) diet for 12 weeks. Skeletal muscle gene expression profiles for genes involved in fatty acid (FA) metabolism were compared between groups after 12 weeks of normal or high Pi diet. To further determine direct effect of Pi on muscle metabolism and expression of genes involved in FA metabolism, additional studies were conducted after subjecting differentiated C2C12 myotubes to media containing 1–3 mM Pi (pH 7.0) to simulate in vivo high phosphate conditions.ResultsIn participants of the DHS (n = 1,603), higher serum Pi was independently associated with reduced time spent in moderate‐to‐vigorous physical activity (p = 0.01) and increased sedentary time (p = 0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared to control diet, consumption of high Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, fatty acid (FA) levels and led to downregulation of genes involved in FA synthesis, release, and oxidation, including Fabp4, Hsl, Fasn, and Pparg in muscle (p<0.05 for all). Similar results are recapitulated in vitro by incubating C2C12 myotubes with high Pi media.ConclusionOur data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle FA metabolism and exercise capacity, which is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ectopic Cardiogenic Transcription Factor Expression Augments the Anti‐fibrogenic Activity of Administered Cardiac Mesenchymal Stromal Cells in a Model of Chronic Ischemic Cardiomyopathy
Authors: Heidel Justin Scott , Fischer Annalara , Sadri Ghazal , Tang Xian‐Liang , Wu Wen‐Jian , Uchida Shizuka , Stowers Heather , Bolli Roberto , Moore Joseph 
Published: June 2021

Preclinical studies suggest that donor cell cardiomyogenic lineage commitment may be an important determinant of the efficacy of cardiac mesenchymal stromal cell (CMC) therapy; however, to what extent myogenic commitment influences CMC cardiac reparative capacity, as well as the underlying mechanisms by which they promote cardiac functional recovery remains poorly defined. In the current study we examine the consequences of enhanced cardiomyogenic lineage commitment on CMC cardiac reparative capacity in vivo and paracrine signaling potency in vitro, via ectopic expression of core cardiogenic transcription factors GMT (GMT: GATA4, MEF2C, and TBX5). Rat CMCs transduced with a tricistronic lentiviral construct harboring GMT coding sequences, or green fluorescent protein (GFP) control, were intramyocardially delivered in a rat model of chronic ischemic cardiomyopathy 30 days after a reperfused myocardial infarction. Indices of cardiac function were assessed by echocardiography and left ventricular (LV) Millar conductance catheterization 35 days after treatment. Infarct size and myocardial collagen deposition were enumerated in coronal‐dissected, cardiac tissue sections by Masson's trichrome or picrosirius red staining, respectively. Cytokine array analyses and in vitro cardiac fibroblast activation assays were performed using conditioned medium (CoMed) derived from either GMT or GFP CMCs, to respectively assess cardiotrophic factor secretion and anti‐fibrogenic paracrine signaling potential. Compared to GFP controls, GMT CMCs exhibited superior ability to attenuate LV systolic dysfunction and myocardial fibrosis in vivo. Proteome cytokine array analyses of CoMed revealed enhanced expression of cytokines with GMT CMCs that function in pathways that regulate matrix remodeling and collagen catabolism. Further, CoMed harvested from GMT CMCs more robustly inhibited Col1A1 synthesis in TGFβ1 activated cardiac fibroblast assays in vitro, compared to that of GFP CMCs. These results provide direct evidence that CMC myogenic lineage commitment biases cardiac repair and, further, that enhanced anti‐fibrogenic paracrine signaling potency may underlie, in part, their improved therapeutic utility.Support or Funding InformationNational Institutes of Health Grant R01 HL141081This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
K475E PRKAG2 Mutation: Cardiac Phenotype and Targeted Therapy Using Rapamycin
Authors: Tseng Yi‐Tang , Wang Zhengke , Padbury James , Phornphutkul Chanika 
Published: June 2021

BackgroundWe identified a novel mutation (K475E) in PRKAG2, coding for protein kinase AMP‐activated non‐catalytic subunit γ2, during a 27‐week prenatal ultrasound. A hypertrophic cardiomyopathy (HCM) phenotype was later confirmed. We have demonstrated in vitro that the K475E mutation led to increases in cardiomyocytes size and area which can be reversed by rapamycin. We have developed transgenic mouse lines with cardiac‐specific expression of the human wild type (TgWT) or K475E mutant (TgK475E) PRKAG2. The TgK475E mice exhibit many human PRKAG2 HCM phenotypes, including cardiac hypertrophy, glycogen overload and sudden death.ObjectiveTo characterize K475E‐induced cardiac phenotype in vivo and develop a targeted therapy using mTOR inhibition strategy for PRKAG2 mutation‐induced HCM.MethodsCardiac hypertrophy was monitored and cardiac glycogen levels were measured at several developmental stages. Neonatal mice (2‐wk old) were treated daily with vehicle or rapamycin (2 mg/kg, ip) for 4 weeks. Cardiac function was monitored longitudinally by echocardiography.ResultsHypertrophy in TgK475E mice was confirmed. Histology revealed large vacuoles and high glycogen content in TgK475E myocytes throughout the ventricles. Echocardiography confirmed that LV mass dramatically increased in TgK475E mice starting from 5 weeks of age. Daily rapamycin treatment for 2 weeks dramatically decreased 1) cardiac hypertrophy and 2) glycogen overload in TgK475E mice. These beneficial effects of rapamycin were significantly tempered, however, when we switched to an alternative dosing regimen (one ip injection/3 days) of rapamycin.ConclusionThe new transgenic mouse model reflects the early onset phenotype of the K475E mutation‐induced HCM in humans. The mTOR signaling pathway is involved in K475E induced HCM. Moreover, the mTOR inhibition strategy as targeted therapy for PRKAG2 induced HCM is effective and should be studied further.Support or Funding InformationThis study was supported by NIH P30GM114750 and the Oh‐Zopfi Research Award, Women & Infant's Hospital.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
OxPCs‐Mediated Lipid Metabolic Responses in Cardiomyocytes as well as During Ischemia Reperfusion Injury
Authors: Bagchi Ashim K , Surendran Arun , Ravandi Amir , Jassal Davinder , Singal Pawan K 
Published: June 2021

Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake through its receptor (LOX‐1) in a variety of physiological and pathological states. We investigated whether the proinflammatory effect of OxPL, generated during stress conditions such as ex‐vivo exposure to POVPC (1‐Palmitoyl‐2‐(5‐oxovaleroyl)‐sn‐glycero‐3‐phosphorylcholine), a derivative of oxidative phosphatidylcholines (OxPCs) of OxPL family and global heart ischemia/reperfusion (I/R), is through the activation of LOX‐1 as well as toll‐like receptor‐2 (TLR‐2). In this study, isolated cardiomyocytes exposed to POVPC as well as isolated rat hearts subjected to global I/R were analyzed. OxPCs‐mediated‐oxidative stress (OS), caused LOX‐1 activation and altered lipid homeostasis. There was an upregulation of TLR2 expression in these conditions, suggesting that TLR2‐mediated inflammation is through LOX1. Furthermore, phosphorylation of sterol regulatory element binding protein 1c (SREBP 1c) was also found be increased due to an increase in OxPCs levels, which is also promoted OS and cell death. On the other hand, LOX‐1 activation also upregulated SREBP1c‐mediated TGF‐βRII expression causing fibrosis. Out of 80 fragmented and non‐fragmented OxPCs followed in a heatmap analysis, 24 in cardiomyocytes and 25 in heart were significantly higher in these stress conditions. Eight (8) of the OxPCs were shared between cardiomyocytes and hearts (FDR < 0.001). Interestingly, one specific fragmented OxPC i.e. 1‐palmitoyl‐2‐azelaoyl‐sn‐glycero‐3‐phosphocholine (PAzPC) among 8 shared OxPCs, was common in both stress conditions. However, a second major fragmented OxPC i.e. 1‐stearoyl‐2‐azelaoyl‐sn‐glycerophosphocholine (SAzPC) was also upregulated in the heart but not in the cardiomyocyte. It appears that cardiomyocyte‐specific; PAzPC and heart‐specific; SAzPC OxPCs may mediate abnormal lipid metabolic responses causing inflammation, apoptosis and fibrosis.Support or Funding InformationCanadian Institutes of Health Research and Research ManitobaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.