bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ageing differentially affects myogenic tone of coronary microcirculatory arteries according to vessel diameter (LB644)
Authors: Mansour Fathi , Hassan Mohammed , Albarwani Sulayma 
Published: June 2021

Aging is the major cause of decline in cardiovascular function and for structural and functional alterations of coronary microvasculature. There is close association between cardiac function and coronary blood flow; hence, age‐associated impairment of cardiac function may be related to reduced coronary blood flow capacity. As myogenic tone has a major role in regulation of local blood flow, the aim of this study was to investigate changes in myogenic tone with aging and its heterogeneity based on resistance arteries size. Coronary resistance arteries from young (3 ‐ 4 months) and old (22 ‐ 24 months) males F344 rats were isolated and mounted on a pressure myograph system and changes in outer diameter in response to alteration of intravascular pressure (0‐100 mmHg) with a 20 mmHg increments under no flow condition were recorded. Myogenic tone calculated as a percentage of the difference between Active (in the presence of calcium) and Passive (in the absence of calcium) diameter over passive diameter for each pressure point. Vessel sizes determined as active outer diameter at 80 mmHg. Values calculated using Student t‐test and expressed as (mean ± s.e.m.). Myogneic tone calculated from arteries of young rats 115 µm ± 9 n= 12 (diameter range; 75 ‐ 167 µm) was significantly higher compared to old one 125 µm ± 9 n = 14 (diameter range; 72 ‐ 186 µm) (p蠄0.001). However, when subdividing vessel sizes into small arteries for young (88 µm ± 4) n= 6 and old (92 µm ± 5) n = 6; and large arteries for young (142 µm ± 6) n= 6 and old (149 µm ± 8) n = 8, the myogenic tone was highly significant when comparing small arteries from young and old (p<0.001) and there was no significant differences in myogenic tone between large arteries. Study findings stating that; Both myogenic tone and response decreased dramatically with aging in small resistance arteries, while increasing in young one. There is a very narrow range of myogenic tone drop, so care must be taken when selecting vessels sizes range for aging studies.Grant Funding Source: Supported by Sultan Qaboos University, Oman
Endothelial cell‐targeted over‐expressing ET‐1 leads to increased blood pressure and decreased heart rate in aged mice (LB655)
Authors: Luo Xin , Xia Zhengyuan , Chung Sookja , Cheung Chi Wai 
Published: June 2021

Endothelin‐1 (ET‐1) is a 21 amino acid vasoconstrictor and implicated in the regulation of hypertention. Recently, our colleagues found that transgenic mice (TET‐1) with endothelial ET‐1 over‐expression developed hypertention in young mice by changing vascular properties. However, the effects of over‐expressing endothelial ET‐1 on cardiovascular system in aged mice are still unclear. Therefore, this study investigated the blood pressure and heart rate of TET‐1 aged mice and non‐transgenic (NTg) aged mice (1.5‐2 years old). A non‐invasive tail cuff measurement showed that a significant elevation of both systolic (115.1 ± 2.935 vs 103.5 ± 1.846 mmHg, p<0.01) and diastolic (85.81 ± 2.303 vs 74.56 ± 2.029 mmHg, p<0.05) in conscious TET‐1 aged mice comparing to NTg counterpart, indicating over‐expressed endothelial ET‐1 cause both systolic and diastolic hypertension in aged mice. And, aged TET‐1 mice showed a significantly decreased heart rate to aged NTg mice (616.7 ± 20.14 vs 670.9 ± 11.57 beats per minute (bpm), p<0.05). Moreover, Rate‐pressure product is a sensitive index of myocardial oxygen consumption, and it was not altered in TET‐1 mice (71085 ± 3258 vs 69337 ± 1233 bpm*mmHg, p>0.05), implicating over‐expressed endothelial ET‐1 would change cardiovascular properties by mechanisms of mutual compensation between blood pressure and heart rate. These findings provide evidence for roles of endothelial ET‐1 in altering cardiovascular system in aged mice. This study also implicates clinical importance of endothelial ET‐1 as a therapeutic target for hypertension in the elderly.Grant Funding Source: Supported by the departmental fund, Department of Anaesthesiology, The University of Hong Kong
Increased β‐adrenergic inotropy in ventricular myocardium from trpm4‐/‐ mice. (LB666)
Authors: Mathar Ilka , Kecskes Miklos , Van der Mieren Gerry , Jacobs Griet , Camacho Londoño Juan E. , Uhl Sebastian , Flockerzi Veit , Voets Thomas , Freichel Marc , Nilius Bernd , Herijgers Paul , Vennekens Rudi 
Published: June 2021

RATIONALE: The Trpm4 gene has recently been associated with several disorders, including cardiac conduction diseases and Brugada syndrome. Transient receptor potential member 4 (TRPM4) proteins constitute Ca(2+)‐activated, but Ca(2+)‐impermeable, nonselective cation channels and are expressed both in atrial and in ventricular cardiomyocytes. The physiological function of TRPM4 in the heart remains, however, incompletely understood.OBJECTIVE: To establish the role of TRPM4 in cardiac muscle function.METHODS AND RESULTS: We used TRPM4 knockout mice and performed patch‐clamp experiments, membrane potential measurements, microfluorometry, contractility measurements, and in vivo pressure‐volume loop analysis. We demonstrate that TRPM4 proteins are functionally present in mouse ventricular myocytes and are activated on Ca(2+)‐induced Ca(2+) release. In Trpm4(‐/‐) mice, cardiac muscle displays an increased β‐adrenergic inotropic response both in vitro and in vivo. Measurements of action potential duration show a significantly decreased time for 50% and 90% repolarization in Trpm4(‐/‐) ventricular myocytes. We provide evidence that this change in action potential shape leads to an increased driving force for the L‐type Ca(2+) current during the action potential, which explains the altered contractility of the heart muscle.CONCLUSIONS: Our results show that functional TRPM4 proteins are novel determinants of the inotropic effect of β‐adrenergic stimulation on the ventricular heart muscle.
Renal P2X receptors mediating pressure‐natriuresis, oxygenation and injury susceptibility (LB721)
Authors: Menzies Robert , Mullins John , Bailey Matthew 
Published: June 2021

Chronic kidney disease (CKD) affects an estimated 1 in 10 individuals and therefore presents a profound socioeconomic burden. The etiology of CKD is undoubtedly multifaceted, remaining largely elusive in spite of a significant focus of basic and translational research, resulting in fibrosis and renal function decline. We have developed models to investigate the pathology of CKD following over‐activation of the renin angiotensin system. In the Cyp1a1‐Ren2 transgenic rat hypertension causes renal injury, predominantly in the preglomerular vasculature. In this model renal injury is characterized by both blood pressure dependent (owing to the antihypertensive affect of Losartan), and blood pressure independent (amelioration of renal injury but not hypertension by spironolactone), mechanisms.Consomic/congenic strain variants identified angiotensin converting enzyme (Ace) as an important gene modifier. Comparative studies of F344 (susceptible) and Lewis (relatively protected) strains by renal microarray revealed the purinergic receptors P2x7 and P2x4 as further candidate modifiers. Gene and protein expression of these P2X receptors were both higher in F344 compared with Lewis. Immunohistochemistry localized P2X7 and P2X4 to the renal vascular endothelium, vasa recta and tubules: between strains the expression pattern only became architecturally distinct in the medulla. Renal functional studies indicated that F344, but not Lewis, responded to acute antagonism of P2X7 and P2X4. F344 showed a significant drop in blood pressure but maintained renal blood flow, indicative of tonic renal vasoconstriction by the vasa recta.Following chronic ANG II infusion into F344 rats, pressure‐natriuresis was impaired and there was a modest increase in blood pressure but no overt injury. Similarly, macrophage infiltration was not significantly increased. Blood oxygenation‐level dependent (BOLD) magnetic resonance imaging (MRI) of the kidney identified a decrease in renal R2* signal following P2X7 and P2X4 antagonism in ANG II infused F344 rats. Together these results suggest that P2X4/7 activation tonically suppress renal perfusion which impairs pressure‐natriuresis and reduces oxygenation. These effects are pro‐fibrotic and may underpin susceptibility to renal injury.Grant Funding Source: British Heart Foundation Centre of Research Excellence (CoRE) Award
Methacholine (M) and resistance exercise training (RET) increase human myofibrillar protein absolute synthetic rate (MPASR) in proportion to increased nutritively perfused mass, belied by steady myofibrillar protein fractional synthetic rates (MPFSR) (LB760)
Authors: Rennie Michael 
Published: June 2021

Michael Clark identified the metabolic power of switching from non nutritive to nutritive flow but for aminoacids (AA) in human leg the situation is complex e.g. leg has ≍35% non muscle lean and fat tissue draining into femoral vein blood. Thus, measures derived from tracer exchange, including Ra, Rd and Net Protein Balance (NPB, ([AAa]‐[AAv]xF)) and MPFSR, are too imprecise to surely detect increases in MPASR unless the % increase in microvascularly perfused muscle is dominant and, or the true muscle mass is known. To research this we measured leg femoral flow (FBF, Doppler) and microvascular blood volume (MBV, CEUS) and components of MPASR groups: 10 men (23 y) fed IV D5W‐AA mix, infused with M (AJP doi: 10.1152); 10 men (72 y) studied postabsorptively and IV fed, pre and post RET (20 w). Unilateral arterial M raised fed state FBF and MBV (126±12% P<0.05; 79±30% P<0.05) causing large but non significant increases (+ ≍50% P=0.26) in NPB. Post RET men showed greater leg strength (+39% P<0.0001) and leg, appendicular and whole body muscle masses (median +1.3‐2.3%, CI 1.1‐16%; RM‐ANOVA, P<0.0001). They also showed greater fed state FBF and MBV than before (+40±11% P<0.05; +44±15% P<0.001) and NPB was larger (+40±16%, P<0.05) despite identical basal FBF and MBV. MPFSR always increased on feeding, but its doubling (P<0.001) and final value (≍0.072%/h) were constant. However for post RET men, knowledge of true DXA muscle mass, corrected for non muscle, revealed significant increases in MPASR (MPFSR x mass x [muscle protein] of 3.2 (2.5‐11.2)%, (median (CI) P<0.01). Thus, likely for M, and certainly for RET, the adaptive response to M and RET is to service fed perfused muscle by increasing AA delivery and thus MPASR.Grant Funding Source: Supported by the Dunhill Medical Trust; I acknowledge my collaborators, K Sjøberg, J P Williams and S Heymsfield, and the technical assistance of P Atherton, M Limb, B E Phillips, A Selby, K Smith and K Varadhan.
Gender and epithelial sodium channel genotype influence the lung fluid response to hypoxic exercise (LB791)
Authors: Baker Sarah , Wheatley Courtney , Taylor Bryan , Johnson Bruce , Snyder Eric 
Published: June 2021

Fluid clearance from the alveolar space is critically dependent on epithelial sodium channels (ENaC). A common polymorphism in the gene encoding the ENaC alpha subunit results in an alanine to threonine substitution (A663T), with higher ENaC channel activity. This variant influences ion and fluid regulation in the lung during exercise and in response to albuterol. We investigated the influence of the threonine variant (T663; AT/TT group) on the lung fluid response to exercise in conditions of normobaric hypoxia, which challenges lung fluid balance. Lung fluid balance was assessed using Exhaled Na+ (ENa+) and the diffusing capacity for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) to determine alveolar‐capillary membrane conductance (Dm). 19 healthy subjects were grouped by ENaC genotype (n=8 vs. 11 for AA and AT/TT, %female=50 vs. 62%, age=27±1 vs. 28±2yrs., ht=171±3 vs. 173±2cm, wt=69±6 vs.72±3kg , BMI=23±1 vs.24±1kg/m2) and completed two overnight visits in a hypoxic tent simulating just over 5,400m. The visits were randomized to inhaled placebo or inhaled amiloride (1.5mg in 5ml normal saline, used to inhibit ENaC activity) with ENa+, DLCO, and Dm assessed at baseline, following 12 hours of hypoxic exposure, and following hypoxic exercise at 65% peak power on a cycle ergometer. We found significant effects of the interaction between gender and ENaC genotype on DLCO, Dm, and Dm corrected for pulmonary capillary blood volume (p<0.05). Specifically, females with the more active T663 variant had a greater diffusing capacity and less ENa+ under placebo conditions, suggesting a greater removal of Na+ and fluid from the airspace. These results suggest that genetic variation of ENaC may influence lung fluid balance during hypoxia and hypoxic exercise.Grant Funding Source: Supported by HL71478, HL108962‐03, and HL007249
Interaction between genetic background and training intensity influences training responses (LB802)
Authors: Avila Joshua , Kim Seung , Massett Michael 
Published: June 2021

The aim of this study was to determine the intensity of exercise training that is required to maximize training adaptations in low responding mice. Male mice from three inbred strains: SJL/J, C57BL/6J, and NON/ShiLtJ completed a graded exercise test before and after four weeks of treadmill running. Mice from each strain were assigned to one of three groups (n=6/group): sedentary control (SED), continuous running (65% of max) and high‐intensity interval training (HIT) (6 x 85% of max for 8 min, 50% of max for 2 min). Exercise capacity was improved by continuous running compared with SED in mice from all strains (P < 0.05). For HIT, only NON/ShiLtJ mice showed a significant improvement in exercise capacity relative to SED mice from that strain. Protein content for PGC‐1alpha, NRF‐1 and mtTFA was examined in plantaris muscle to assess the metabolic adaptation to the different intensities of exercise training. Overall, exercise training induced relatively small changes in protein content in the plantaris. For SJL/J and NON/ShiLtJ, PGC‐1alpha tended to be double in plantaris from HIT compared with sedentary and unchanged in plantaris from C57BL/6J. Tfam protein content was also nearly double in muscle for HIT in SJL/J and C57BL/6J strains compared with sedentary. These data indicate that adaptations to training in skeletal muscle proteins are not directly related to changes in exercise capacity.Grant Funding Source: Supported by NIH grant HL085918 to MPM
Relation of genetic polymorphisms and nutrient with bone density and skeletal muscle mass in Japanese young women (LB805)
Authors: Kondo Hiroyo , Fujino Hidemi , Nagatomo Fumiko , Ishihara Akihiko 
Published: June 2021

Osteoporosis and sarcopenia are complex diseases characterized by low bone density and muscle mass, respectively, The purpose of this study was to assess the interactive effects of habitual exercise, nutrient intake and gene polymorphisms of Vitamin D receptor (VDR), estrogen receptor alpha (ESR1) and ciliary neurotrophic factor (CNTF) on bone density and skeletal muscle mass. 240 Japanese healthy young women (20‐23 yr) were recruited in this study. Habitual exercise and nutrient intake were assessed using a questionnaire. Bone density and muscle mass were measured by a quantitative ultrasound method and whole body impedance, respectively. In addition, the polymorphisms of ESR1, VDR and CNTF were genotyped using a TaqMan based real‐time PCR method. The skeletal muscle mass was correlated with calcium intake although there was no relationship between protein intake. Interestingly, the subjects with ESR1 allele A and VDR allele C in the habitual exercise subjects had significantly higher bone density than those in the non‐habitual exercise subjects . In addition, the skeletal muscle mass in non‐habitual exercise subjects with AA homozygote in CNTF was higher than that in TT. Thus, habitual exercise and calcium intake are more important for bone metabolism and skeletal muscle mass carrying ESR1 A and VDR C, allele. These results suggest that genetic polymorphisms were significantly associated with bone density and muscle mass in young women. Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology.Grant Funding Source: Supported by Japanese MEXT
Inflammation following muscle injury promotes myoblast proliferation (LB808)
Authors: Lees Simon , Niccoli Sarah , Hawdon Nicole , Sarvas Jessica , Frye Melinda , Chicco Adam , Otis Jeffrey 
Published: June 2021

Objective: To determine the expression of IL‐1β and IL‐6 at several time points following injury, and their effects on myoblast proliferation. Experimental Design: Skeletal muscle was injured using BaCl2 in mice and tissue was collected 1, 5, 10, and 28 days following injury. Cytokine expression was determined using real time RT‐PCR. Mechanisms of cytokine‐induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. Results: ~20‐fold increase in IL‐1β (p<0.05) and IL‐6 (p=0.06) expression was observed 5 days following injury. IL‐1β increased proliferation of both primary and C2C12 myoblasts ~25%. It was determined that IL‐1β not only stimulated NF‐B activation, but this signalling was required for the mitogenic effect of IL‐1β. These data demonstrate for the first time that IL‐1β alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offers insight into the mechanisms dictating satellite cell function following injury.Grant Funding Source: Supported by NIH‐NIA (R03 AG‐034352, P.I., SJL), NIH‐NIAAA (K01 017190, P.I., JSO), NOHFC (P.I., SJL
Electron microscopy studies elucidate morphological forms of Chlamydia pneumoniae in blood samples from patients diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (LB81)
Authors: Brandt James , Cader Ahmad , Semler Lauren , Hammond Christine , Bell Marcus , Devins Morgan , Smith Jenayle , Joseph Nicol , Velez Marisol , Galluzzi Katherine , Balin Balin , Appelt Denah 
Published: June 2021

Our previous studies of brain tissues obtained at autopsy have established an association of Chlamydia pneumoniae (Cpn) infection with late‐onset Alzheimer’s disease (AD). Given these findings, we have designed a study using electron microscopy (EM) to determine if various forms of Cpn from geriatric patient’s blood samples could be identified and correlated with cognitive decline associated with AD.Patients, >65 years old, and who participated in this IRB approved study, met well‐defined exclusion criteria prior to being evaluated for cognitive status using the SLUMS and FAST testing assessments. After psychometric testing, blood was drawn from the patients and these samples were prepared for EM and assessed for the presence of Cpn.Our ultrastructural analysis revealed evidence for the presence of Cpn in peripheral blood cells from 12 patients correlated with MCI and AD. Intravacuolar reticulate bodies, elementary bodies, and intermediate bodies characteristic of Cpn were observed in leukocytes from the buffy coat. More specifically, we observed the classical “pear‐shaped” elementary bodies characteristic of Cpn. Immuno‐ EM was performed for positive identification of these various forms of Cpn.Our data indicate that screening for Cpn from blood samples may prove to be a viable biomarker in differentiating cognitive change consistent with stages associated with MCI and AD. Investigating the distinct morphologies of Cpn in human blood samples from the geriatric population by EM, with other frontline diagnostic procedures, may clarify the diagnosis of MCI and late onset AD.Grant Funding Source: Center for Chronic Disorders of Aging
Ontogeny of genetic networks underlying central appetite‐controlling systems in the teleost Atlantic cod (LB830)
Authors: Rønnestad Ivar , Le MTDH , Ebbesson Lars , Karlsen Ørjan , Angotzi Anna Rita 
Published: June 2021

We examined the distribution of Neuropeptide Y (NPY), cocaine‐ and amphetamine‐regulated transcript (CART) and prepro‐orexin (pOX) in the brain of Atlantic cod by in situ hybridization from onset of exogenous feeding (4days post hatch, dph) to postlarval stage (76dph). All examined genes were expressed from 4dph and displayed temporal and spatial differences in expression during development. pOX mRNA was only expressed in hypothalamus. NPY and CART mRNA expressions had broad distributions in the brain, including telencephalon, diencephalon, and optic tectum. In addition, NPY transcripts were found in the preoptic region, while CART was found in medulla oblongata. New populations of CART positive neurons appeared in olfactory bulb, in the region of the nucleus of medial longitudinal fascicle, and later in midbrain tegmentum. We found several examples of co‐expression (NPY‐CART) and (CART‐pOX). Distributions of NPY and pOX transcripts suggest that telencephalon and hypothalamus are involved in stimulation of feeding in cod. Expression of CART indicates that “satiety centers” are located in hypothalamus, thalamus and medulla oblongata.Grant Funding Source: Supported by Research Council of Norway‐ CODE 199482
CXCR4‐CXCL12 axis in proliferation, migration, and invasion of endometriosis (LB850)
Authors: Ruiz‐Rivera Abigail , Monteiro Janice , Colon Mariano , Echevarria Martha , Fazleabas Asgerally , Flores Idhaliz 
Published: June 2021

Endometriosis a benign gynaecological disease, associated with chronic inflammation and increased levels of chemokines. Lesions are composed of endometrial stroma and glands localized outside the uterus. In a rat model of endometriosis, we showed high CXCR4 mRNA levels in endometriotic lesions and in high protein expression levels in human endometriosis tissues compared to control endometrium . The CXCR4‐CXCL12 axis plays roles in proliferation, migration, and cell invasion. Endometriotic epithelial cells expressed CXCR4. We hypothesized that CXCL12 may induce proliferation, migration, and invasion of endometriotic cells (12Z) compared to a non‐invasive breast cancer cells, expressing endometrial markers (EEC), and the induction may be blocked by the CXCR4 inhibitor, AMD3100. Cell proliferation in response to CXCL12 was analyzed by BrdU assay. We also studied cell invasion and migration in response to CXCL12 and AMD3100 by invasion and migration chambers. Rat model of endometriosis was used to identify the effect of AMD3100 in lesions regression. CXCL12 increased proliferation and migration of EEC, and invasion in 12Z cells, compared to media (p<0.05). AMD3100 reduced migration in EEC; reduced migration and increased invasion in 12Z cells (p<0.05). These data suggest that the CXCR4‐CXCL12 axis can be activated in endometrial cells to promote cell proliferation, migration, and invasion, and application of cancer treatments to endometriosis disease requires additional studies. These biological functions have been previously shown to be dysregulated in endometriosis, by still undefined mechanisms, leading to survival and growth of ectopic endometrium.Grant Funding Source: Supported by F31HD072594, RCMI G12‐MD007579, R25GM082406, R25GM096955, R01‐HD050509