bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Roux‐en‐Y Gastric Bypass Surgery on Mitochondrial Quality Control Proteins in Human Myotubes Derived from Severely Obese Humans
Authors: Kugler Benjamin N. , Gona Philimon N. , Saunders Sasha N. , Park Sanghee , Dubis Gabe , Houmard Joseph A. , Zou Kai 
Published: June 2021

Impaired skeletal muscle glucose oxidation in response to insulin is a hallmark characteristic of humans with severe obesity and Type 2 Diabetes. Roux‐en‐Y gastric bypass (RYGB) surgery is an effective treatment of these metabolic diseases by markedly improving metabolic health, including enhanced glucose oxidation and insulin action in skeletal muscle. However, the underlying mechanisms responsible for these improvements are not fully understood. Skeletal muscle mitochondria are critical in preserving cellular health, but exhibit defective functions in severely obese humans. Recent studies have suggested that dysregulated mitochondrial dynamics are associated with mitochondrial dysfunction and insulin resistance. This study aims to determine the effects of severe obesity and RYGB surgery on mitochondrial dynamic proteins and its association with insulin sensitivity and glucose oxidation in human skeletal muscle. Human skeletal muscle cell culture model was utilized by isolating human skeletal muscle cells from muscle biopsies obtained from lean subjects (n=6, BMI = 22.7 ± 1.2 kg/m2, HOMA‐IR = 1.9 ± 0.4) and RYGB patients prior to, 1‐month and 7‐months following surgery (n=6, BMI = 47.3 ± 2.8 kg/m2, 41.0 ± 2.9 kg/m2, 33.7 ± 2.2 kg/m2, HOMA‐IR = 3.4 ± 0.4, 2.9 ± 0.9, 1.7 ± 0.2, respectively). Human skeletal muscle cells were differentiated to myotubes. On day 7 of differentiation, myotubes were harvested for immunoblot analysis in order to assess the expressions of mitochondria dynamics proteins. Myotubes derived from severely obese patients had a 35% increase in mitochondrial fusion protein Optic Atrophy 1 (Opa1) expression before surgery when compared to lean controls (p <0.05). In addition, there was a trend towards a decrease of fusion proteins Opa1 and Mitofusin 1 (Mfn1) expressions in myotubes derived from the same patients at 7‐months following surgery (26% and 18%, p=0.065, respectively) in comparison to pre‐surgery state, and virtually no difference from lean controls. Furthermore, Opa1 expression negatively correlated with insulin‐stimulated glucose oxidation in myotubes (r = −0.614, p <0.05), while Mfn1 is positively correlated with HOMA‐IR (r = 0.495, p <0.05). Mitochondrial fission and mitophagy proteins observed no differences between lean, pre‐surgery, 1‐month and 7‐months following RYGB surgery. In conclusion, these data suggest that RYGB surgery corrected severe obesity‐induced dysregulation in mitochondrial fusion process in human myotubes, which may contribute to improved insulin sensitivity and skeletal muscle glucose oxidation in RYGB patients.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Tendon developmental plasticity and functional regeneration
Authors: Galloway Jenna L. , Niu Xubo , Shah Rishita R. , Nerurkar Nandan L. , Noedl Marie 
Published: June 2021

Tendons enable movement by transferring force from muscle to bone. They are comprised of a highly organized collagen‐rich extracellular matrix. Disruption to the development and maintenance of tendons can lead to birth defects and result in injury in adults. We currently have an incomplete understanding of how tendons interact with their neighboring tissues to regulate the development and morphogenesis of the musculoskeletal system. In addition, once mature mammalian tendon tissue is formed, it has limited regenerative potential after injury. Central to this challenge is to uncover new mechanisms underlying tendon cell regulation during musculoskeletal development and regeneration. To accomplish this, we have turned to the zebrafish system because it is highly regenerative and amenable to genetic manipulations and live imaging. We have previously demonstrated that zebrafish tendons have molecular, developmental, morphological and biomechanical similarities to mammalian tendons, thereby making them an excellent vertebrate model to study tendon biology. However, no study has investigated their capacity to regenerate their tendons. Using the zebrafish, we developed methods to perform genetic tendon cell ablation, lineage tracing, live imaging, and mechanical testing to determine if developing and adult zebrafish can regenerate their tendon tissues. Following tendon cell ablation in developing zebrafish embryos, we observe defects in tendon gene expression and ECM composition. Cartilage and muscle tissue morphology was also disrupted following tendon cell loss. Tendon cells and the collagen organization returned after 1–2 weeks and 1–2 months, respectively. Interestingly, the pattern of the attachment sites was also restored, indicating the presence of regulatory programs that recruit and/or promote tendon cell proliferation and differentiation at the previous attachment sites. We are currently focused on identifying the developmental origins of the regenerating tendon cells and the pathways restoring the attachment site pattern. In addition to embryonic tendon regeneration, we also found that adult zebrafish appear to regenerate their collagen organization and mechanical properties after an acute physical injury. Together, our work demonstrates robust tendon regeneration at embryonic and adult stages in the zebrafish. These studies also provide a system to examine the morphogenetic and molecular events underlying tendon regeneration and musculoskeletal tissue‐tissue interactions, which has significance for regenerative biology approaches to musculoskeletal injuries.Support or Funding InformationNICHD HD06953, NIDCR DE024771, Charles H. Hood Foundation, HSCI Seed GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Renal sympathetic nerve contribute to high blood pressure in male PCOS offspring
Authors: Maranon Rodrigo Oscar 
Published: June 2021

Prenatal factors may program elevated blood pressure in offspring of women with polycystic ovary syndrome (PCOS). We recently determined in an experimental model of PCOS that their male offspring have elevated blood pressure compared to offspring of controls. Existing evidence shows that PCOS women may have increased renal sympathetic nerve activity (RSNA) which contributes to their elevated blood pressure. However, whether the elevated blood pressure in PCOS offspring is due to activation of the renal sympathetic nervous system (RSNS) remains undetermined. We hypothesized that activation of the RSNS contributes to the increase in blood pressure in male PCOS offspring. PCOS dams were treated with DHT pellets (DHT pellet 7.5mg/90d) beginning at 4 wks of age and continuing through pregnancy and lactation. Controls were given placebo pellets. Male PCOS offspring (mPCOS‐off) and male control offspring (mCon‐off), 20 weeks of age, were subjected to renal denervation (RD) (cutting renal nerves bilaterally and painting with 10% phenol in ethanol) or sham surgery (movement of the kidneys) (n=9/grp): mPCOS‐off‐sham, mPCOS‐off‐RD, mCon‐off‐sham, and mCon‐off‐RD, respectively. Baseline mean arterial pressure (MAP, telemetry) was significantly higher in mPCOS‐off‐sham than mCon‐off‐sham (124±1 mmHg vs. 119±1 mmHg; p<0.05). After recovery from renal denervation or sham and telemetry implantation for 14 days, MAP was decreased with renal denervation in mPCOS‐off‐RD (mPCOS‐sham: 124±1 vs mPCOS‐RD: 111±2 mmHg, p<0.05) but not in control offspring (mCon‐off‐sham: 119±1 vs mCon‐RD: 118±3 mmHg; p=NS). Thus, male PCOS offspring have an increase in MAP compared to the male control offspring, and renal denervation reduced their blood pressure, suggesting that exposure to hyperandrogenemia in utero may activate the RSNS later in life, which could contribute to high blood pressure. These data suggest that children of women with PCOS should closely monitor their blood pressure as they age to maturity.Support or Funding InformationSupported by AHA14POST18640015 and P20GM121334 (ROM).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Uncoupling of Feedforward Control on Blood Pressure by Heart Rate in Patients with Recent Myocardial Infarction
Authors: Badhwar Smriti , Chandran Dinu , Jaryal Ashok , Narang Rajiv , Patel Chetan , Deepak Kishore Kumar 
Published: June 2021

BackgroundMechanically induced respiratory synchronous thoracic pressure fluctuations produce High Frequency(HF) BP oscillations. In addition, HF oscillations in BP are also modulated through feedforward coupling with Heart Rate(HR). Reduced baroreflex sensitivity, heart rate variability (HRV) and blood pressure variability (BPV) is known to be associated with increased mortality after Myocardial Infarction(MI).ObjectiveThe objective of the study was to assess the LF and HF oscillations in HR and BP and their associations in patients of recent MI with and without scar.MethodsNon‐invasive beat‐to‐beat BP measurement using Portapres® with simultaneous recording of Lead II ECG was used to assess short term (5min) HRV and BPV. Thirty‐two patients of recent MI (≤6 months) were divided into those with scar (S) (n = 21, age 54.3±10.7years) and those without scar (NS) (n = 11, age 54.7±9.22years) on the basis of myocardial perfusion imaging (MPI) using single photon emission computed tomography. Transfer function analysis was done using BP as the input variable and HR as the output variable. The signals were linearly interpolated and resampled at 1Hz. The series was subdivided into 256‐point segments with 50% overlap for spectral estimation. The coherence, gain and phase was calculated for the LF (0.04–0.15) and HF (0.15–0.4) band. LF and HF gain and phase was evaluated only if coherence between the two signals was >0.3.ResultsLF and HF HRV were similar between the two groups (LF normalized units (nu) S vs NS 53.6±22.4 vs 54.7±18.1, HF nu S vs NS 35.9±17.9 vs 36.0±12.0). Similarly, LF nu Systolic BPV was comparable between the two groups (S vs NS 66.7±17.2 vs 57.9±15.9). HF nu systolic BPV was significantly lower in the S group compared to the NS group [S vs NS 28.3(13.4–39.3) vs 39.1(19.8–46.5) p = 0.04]. LF and HF gain was also similar between the two groups [LF gain S vs NS 5.24±2.25 vs 5.86±3.09, HF gain S vs NS 7.19(3.26–10.4) vs 8.40(5.94–13.5) ms/mmHg]. There was no significant difference in the LF phase between the two groups (S vs NS 1.55±0.39 vs 1.13±0.61 radians). However, HF phase coupling of BP with HR of the S group was significantly more positive than the NS group (S vs NS 0.39±0.92 vs −0.61±1.0 radians p = 0.02).ConclusionHRV was comparable between the scar and no scar group however HF oscillations in BPV are attenuated in patients with irreversible damage to cardiac tissue when compared to those in whom it is preserved. The positive phase in HF in the scar group could possibly be indicative of a feedforward uncoupling between HR and BP in the scar group while the same is preserved in the no scar group.
Neurons in a Subregion of the Medial Parabrachial Nucleus (mPBN) Attenuate the Gain of the Hering‐Breuer (H‐B) Reflex
Authors: Zuperku Edward J. , Stucke Astrid G. , Tomlinson Jack , Krolikowski John G. , Hopp Francis A. , Stuth Eckehard A. 
Published: June 2021

This study provides new evidence showing that a subregion of the mPBN, which plays a key role in the control of breathing frequency (1), also attenuates the H‐B expiratory facilitatory reflex. Experiments were performed in decerebrate, vagotomized dogs during isocapnic hyperoxia. Phase durations TI and TE were obtained from the phrenic neurogram(PNG). A small concentric bipolar electrode was used to microstimulate the mPBN subregion. Lung inflations and/or weak electrical stimulation of a desheathed cervical vagus nerve were used to activate the slowly adapting pulmonary stretch receptors (PSRs) to produce the H‐B reflex. Pulse‐train PSR stimulation at various frequencies (Fs) were delivered during the E‐phase of test cycles separated by several non‐stimulated control cycles. During every other PSR test cycle, pulse‐train stimulation of the pontine subregion at a predetermined frequency was concurrently delivered to determine its effect on the PSR‐induced increase in TE (e.g., fig A). The effect of the pontine stimulus in the absence of the PSR input was also measured. Plots of TE vs. PSR step Fs have the shape of an increasing exponential function. The effect of the pontine input was a proportional reduction in TE at each of the PSR step Fs, and was shown as an attenuated curve in the TE‐Fs plots (fig B). The relationship between the reduction in the H‐B reflex and the pontine stimulus frequency was linear over the range of 0 to 20 Hz, with a maximum attenuation of the H‐B reflex to ~20% of control (no pontine stimulus) produced by pontine stimulus frequencies in the 20–40 Hz range. These findings suggest that as inputs from the pontine subregion increase breathing frequency, this region concurrently attenuates the H‐B expiratory facilitatory reflex. This mechanism counteracts the PSR‐induced increase in TE, which reduces breathing frequency.Support or Funding InformationSupported by VA grant 2 I01BX000721‐07This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Veins Are Essential for Arteries: Immune Cells Implication
Authors: Champin Tristan , Grenier Céline , Munier Mathilde , Henrion Daniel , Loufrani Laurent 
Published: June 2021

Shear stress produces arterial diameter expansion associated with an hypertrophy induced by inflammation, macrophages, neutrophils or lymphocytes cells. Furthermore, arteries and veins are often associated through perivascular fat, allowing transfer of immune cells between both possible.So, we investigated the vein implication on immune cells recruitment for arterial remodeling of 12 weeks C57BL6/J mice. We produced various ligation models in mesenteric arteries or common carotids to produce High Flow Arteries (HFA). For each model, mesenteric or jugular veins associated with the HFA are ligatured or not.In resistance arteries, the absence of the vein associated with HFA, prevents HFA remodeling (HFA Ctrl: 320μm±27 vs HFA without vein: 218μm±19). Also, in conductance arteries, jugular ligation associated with HF carotid is able to prevents remodeling. qRT‐PCRs experiment have shown an increase of VCAM1 expression in veins during high‐flow mediated arteries remodeling. Vein ligation increase oxidative stress production. ROS generate a SIRT1 transcriptional activation leading to a decrease of VCAM1 expression. Immunostaining analysis, show that neutrophils and macrophages migrate from vein to artery. Immune cells are early recruited in vein but diapedesis modification is modulated by VCAM1 expression on vein endothelium.To conclude, we demonstrated for the first time that artery and vein interact each other by perivascular fat to generate mesenteric and conductance arteries remodeling.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Type 2 Diabetic Coronary Vascular Smooth Muscle Cells Exhibit Decreased Stiffness and Decreased Adhesion
Authors: McCallinhart Patricia , Sun Zhe , Meininger Gerald A. , Trask Aaron J. 
Published: June 2021

We previously reported that type 2 diabetic (T2D) coronary resistance microvessels (CRMs) undergo early inward hypertrophic remodeling with reduced vessel stiffness that is associated with a proliferative VSMC phenotype. We also previously revealed that there is no difference in stiffness of decellularized CRMs from diabetic (db/db) and normal (Db/db) mice, suggesting that the decreased stiffness of the intact diabetic CRM is not due to alterations in the extracellular matrix (ECM) of those microvessels. Given that diabetic CRMs are less stiff and this decreased stiffness does not appear to be due differences in the mechanical strength of the surrounding ECM, the aim of the current study was to determine whether a reduction in cellular mechanical stiffness between Db/db and db/db CRM vascular smooth muscle cells (VSMCs) may be responsible. VSMCs were isolated from 16 week old Db/db and db/db mice and passage 1 cells were used for all experiments (n=6–7 for all groups). Using an atomic force microscope with probes coated with fibronectin (FN), a nano‐indentation protocol was used to measure cellular stiffness and adhesion to FN. Elastic modulus, a measurement of cellular stiffness, was reduced in diabetic coronary VSMCs compared to normal (Db/db: 6.74 ± 0.40 kPa vs. db/db: 4.96 ± 0.35 kPa, p = 0.004). By comparison, there were no significant differences in elastic modulus between normal and diabetic aortic VMSCs (Db/db: 5.39 ± 0.79 kPa vs. db/db: 5.18 ± 0.87 kPa, p = 0.861). Additionally, diabetic coronary VSMCs had reduced adhesive force to fibronectin compared to normal coronary VSMCs (Db/db: 54.78 ± 5.49 vs. db/db: 39.8 ± 3.43 pN, p = 0.03). In a separate experiment, qPCR was performed on mRNA from normal and diabetic CRM VSMCs. Alpha‐smooth muscle actin trended lower in db/db CRM VSMCs (p=0.07), indicating a de‐differentiated phenotype. Cell cycle regulator, p53, had significantly reduced mRNA expression in the diabetic coronary VSMCs over control VSMCs (Db/db 1.00±0.06 vs. db/db 0.63±0.08, p<0.01). These data show that reductions in cellular stiffness and adhesion to the ECM of diabetic CRM VSMCs may underlie ex vivo whole microvessel mechanical properties to account for reduced CRM stiffness. The changes in diabetic coronary VSMC stiffness and adhesion may be the result of VMSC phenotypic switching to a more de‐differentiated/proliferative phenotype.Support or Funding InformationSupport: NIH R00 HL116769 and S10 OD023438 and Nationwide Children's Hospital to AJTThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Microvascular Endothelial Function across the Cancer Survivorship Continuum
Authors: Banister Heather R. , Sutterfield Shelbi L. , Caldwell Jacob T. , Post Hunter K. , Lovoy Garrett M. , Ade Carl J. 
Published: June 2021

BackgroundChemotherapy for the treatment of various cancers has previously been shown to have direct cardiotoxic effects. However, changes in endothelial function due to chemotherapy‐induced toxicity in cancer survivors during the years following treatment remains poorly understood. Therefore, the purpose of this study was to evaluate microvascular endothelial‐dependent vasodilation across the cancer survivorship continuum as well as in healthy controls. We hypothesized that early cancer survivors would yield a decreased percent change in skin blood flow and cutaneous vascular conductance when compared to late survivors and controls.MethodsTo date, thirteen female cancer survivors and thirteen healthy controls (cancer free with no history of chemotherapy) participated in this study. Of the cancer survivors nine were defined as early survivors (within 5 years of chemotherapy treatment) and four as late survivors (> 5 years post chemotherapy treatment). Skin blood flow (SkBF) was measured via integrated laser Doppler flowmetry. Mean arterial pressure (MAP) was measured and used to calculate cutaneous vascular conductance (CVC = SkBF/MAP *100). Endothelium‐dependent cutaneous microvascular function was determined as the percent change in SkBF and CVC in response to iontophoresis of 2% acetylcholine (ACh).ResultsThere were no differences in age between groups (early vs. late: P=0.8; late vs. control: P=0.7; early vs. control: P=0.8). The hyperemic responses for SkBF (early: 1081 ± 718% Δ; late: 1458 ± 653% Δ; P=0.4) and CVC (early: 1060 ± 694% Δ; late: 1499± 751% Δ; P=0.5) were not significantly different between early and late cancer survivors. Similarly, the SkBF (early: 1081 ± 718% Δ; control: 1554 ± 655% Δ; P=0.3) and CVC (early: 1060 ± 694% Δ; control: 1472 ± 626% Δ; P=0.1) were not significantly different in the early cancer survivors compared to controls. There was no significant difference in SkBF (late: 1458 ± 653% Δ; control: 1554 ± 655% Δ; P=0.8) and CVC (late: 1499± 751% Δ; control: 1472 ± 626% Δ; P=0.9) between late cancer survivors and controls.ConclusionEndothelium‐dependent cutaneous microvascular function is not different between early cancer survivors compared to those >5 years post‐chemotherapy and healthy controls. These results suggest that microvascular endothelial function is restored in the early years following chemotherapy and is maintained in later years of survivorship. Additional work is required to determine if endothelial dysfunction occurs in other important vascular beds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glucose‐Derived Microparticles Induce Adhesion Molecule Surface Expression on Endothelial Cells
Authors: Bammert Tyler D. , Hijmans Jamie G. , Stockelman Kelly A. , Brewster Lillian M. , Greiner Jared J. , DeSouza Christopher A. 
Published: June 2021

Clinical interest in endothelial‐derived microparticles (EMPs) has increased due to their role in the pathogenesis of vascular disease. Hyperglycemic conditions, such as diabetes, are known to stimulate EMP release; however, the effects of these glucose‐derived microparticles on endothelial health and function are not fully understood. The aim of this study was to determine, in vitro, the effects of glucose‐induced EMPs on endothelial cell expression of the following adhesion molecules: E‐selectin, intercellular cell adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and platelet cell adhesion molecule‐1 (PECAM‐1). Human umbilical vein endothelial cells (HUVECs) were cultured (3rd passage) and plated in 6‐well plates at a density of 5.0 × 105 cells/condition. HUVECs were incubated with media containing either 25 mM D‐glucose (concentration representing a hyperglycemic state) or 5 mM D‐glucose (normoglycemic condition) for 48 hr to generate EMPs. EMPs derived from both conditions were pelleted by centrifugation and resuspended in culture media. Characterization and concentration of EMPs was determined by flow cytometry using VE‐Cadherin (CD‐144‐PE). To determine cell adhesion molecule expression, HUVECs (3 × 106 cells/condition) were treated with either high glucose‐derived EMPs (hgEMPs) or normal glucose‐derived EMPs (ngEMPs) for 24 hr and surface expression of E‐selectin (CD62E‐PE), ICAM‐1 (CD54‐FITC), VCAM‐1 (CD106‐APC) and PECAM‐1 (CD31‐BV) was assessed by flow cytometry and reported as mean fluorescent intensity (MFI). The high glucose condition induced markedly higher (~260%; P<0.05) EMP release compared with normal glucose (136±38 vs. 37±13 MP/μL). Surface expression of E‐selectin (2614±132 vs. 2010±204 MFI), ICAM‐1 (2110±81 vs. 1688±152 MFI), and PECAM‐1 (4237±395 vs. 2525±269 MFI) on endothelial cells were significantly higher in the hgEMP treated compared with ngEMP treated cells. VCAM‐1 expression was not significantly different between cells treated with hgEMP (3741±680 MFI) or ngEMPs (2340±546 MFI). These results demonstrate that high glucose‐derived EMPs markedly increase endothelial cell expression of E‐selectin, ICAM‐1 and PECAM‐1. Elevations in endothelial expression of these cell adhesion molecules has been shown to be associated with both the development and progression of atherosclerosis. Microparticle‐induced cell adhesion molecule expression provides potential novel mechanistic insight regarding the heightened and accelerated risk of atherosclerotic vascular disease associated with hyperglycemia.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.