bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Ceramide Signaling to Activation of the mTORC1 Pathway and Calcification Nidus Formation in Coronary Arterial Smooth Muscle Cells
Authors: Bhat Owais M , Huang Dan‐Dan , Yuan Xinxu , Kukreja Rakesh C , Li Pin‐Lan
Published: June 2021

The mammalian target of rapamycin complex 1 (mTORC1) signaling on late endosomes (LE)/lysosomes may control cargo selection, membrane biogenesis, exosome secretion and lysosome trafficking, which is fine controlled by lysosomal sphingolipids such as ceramide. This lysosomal sphingolipid‐regulated mTOR signaling may be a crucial molecular mechanism responsible for development of the arterial medial calcification (AMC) given the crucial role of exosome secretion from vascular smooth muscle cells (SMCs). In the present study, we used coronary artery SMCs (CASMCs) from Asah1fl/fl/SMcre mice with SMC‐specific deletion of lysosomal acid ceramidase (mouse gene code: Asah1) to demonstrate the role of lysosomal ceramide in mTOR signaling and arterial calcification. First, we demonstrated that mTORC1, a 289 kD cytoplasm protein is enriched in CASMCs by Western blot analysis and treatment of CASMCs isolated from Asah1fl/fl/SMcre mice with high Pi increased more calcium deposition compared to WT/WT cells as shown by the presence of Alizarin Red‐stained nodules. This calcium deposition was significantly decreased by specific mTOR inhibitor (Torin‐1) and by acid sphingomyelinase (Asm) inhibitor (Imipramine). Correspondingly, Asah1 gene deletion induced phenotypic change in Pi‐treated CASMCs, as depicted by decreased SM22‐α (SMC marker) expression in Western blot analysis, which was reversed by Torin‐1 or Imipramine. Using confocal microscopy, we further found that Pi markedly increased colocalization of mTORC1 with Lamp‐1, a lysosome targeting of mTORC1, but decreased colocalization of VPS16 with Lamp‐1, an indicative of multivesicular bodies (MVBs) interaction with lysosomes in CASMCs from Asah1fl/fl/SMcre mice, suggesting that activation of mTOR signaling inhibits lysosome trafficking or fusion with MVBs if AC was deficient. However, mTOR and Asm inhibition produced opposite effects on lysosome trafficking and interaction with MVBs compared to CASMCs treated with AC deficiency, further suggesting the role of ceramide‐mTOR signaling in lysosome trafficking or interactions with MVBs. Using nanoparticle tracking analysis, Pi‐induced excretion of exosomes (100–150 nm in size) were found to be significantly increased in CASMCs of Asah1fl/fl/SMcre mice compared to CASMCs from their control littermates. These results suggest that lysosomal ceramide‐mTOR signaling critically controls MVB fate and exosome release and that AC deficiency may lead to increased mTOR activation, thereby increasing exosome release and leading to calcification nidus formation in CASMCs.

Support or Funding Information

(Supported by NIH grants HL057244, HL075316 and DK120491)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Carbon Nanotubes and Crystalline Silica Stimulate Matrix Remodeling and Contraction by Inducing Myofibroblast Transformation in a Three‐Dimensional Culture of Human Pulmonary Fibroblasts: Role of Dimension and Rigidity
Authors: Ma Qiang , Hindman Bridget
Published: June 2021

Pulmonary fibrosis is a poorlyunderstood pathologic condition. Carbon nanotubes (CNTs) are nanomaterials withpotentials for broad applications. CNTs can induce pulmonary fibrosis inanimals, a cause for concern for exposed workers and consumers. Giventhe large number of CNTs available on the market and the seemingly infinitenumber of ways these particles can be modified in ways that may affecttoxicity, in vitro models that can be used to quickly and effectively investigatethe relative fibrogenicity of CNTs are much needed. Here we analyzed thefibrogenic potentials of six CNTs of varying physical properties, as well ascrystalline silica, using two and three‐dimensional (2D and 3D, respectively) in vitro models. WI38‐VA13 human pulmonary fibroblasts were treated with CNTs orsilica, with TGF‐β1, a known inducer of fibroblastdifferentiation, as positive control. The cells were examined for fibroticmatrix alterations, including myofibroblast transformation, matrix remodeling, and matrix contraction. While all tested CNTs induced myofibroblastdifferentiation in 2D and 3D cultures, the 3D culture allowed the examinationof myofibroblast clustering, collagen deposition and rearrangement, celldivision, and matrix contraction in response to fibrogenic exposures, processescritical for fibrosis in vivo. At 1 μg/ml, multi‐walled carbon nanotubes (MWCNTs) elicit higherinduction of myofibroblast differentiation and matrix remodeling than single‐walledcarbon nanotubes (SWCNTs). Among MWCNTs, those with the highest and lowestaspect ratios produced the largest effects, which were comparable to those byTGF‐β1 and higher than those by silica. Thus, the 3D collagen‐based modelenables the study of matrix fibrotic processes induced by CNTs and silicaparticles directly and effectively. This in vitro approach to analyzingfibrogenic activities of inducers is applicable to a variety of fibrogenicagents including particles, fibers, nanomaterials, and soluble inducers.

Support or Funding Information

Supported by a grant for Q.M. from the Health Effects Laboratory Division and the Nanotechnology Research Center at National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, USA.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Exercise training‐induced enhancement of coronary vasodilatory function is absent in rats lacking the transcription factor, Nrf2
Authors: Ballehr Kelsey Lynn , Park Hyerim , Restrepo Alexis , Dewell Isabella , Wahl John , Wahl Jake , Vega‐Figueroa Leilanie , McKinley‐Caspanello Carly , Maraj Joshua , Peterson William , Reid‐Foley Emily , Bedwell Kristin , Schwartz Kaley , Sadowsky Dylan , Delp Michael , Geurts Aron , Medarev Steven , Muller‐Delp Judy
Published: June 2021

Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is a transcription factor that is crucial in maintaining cellular redox homeostasis. Aerobic exercise training has been reported to enhance vasodilatory responses of coronary arterioles through signaling that involves reactive oxygen species. We hypothesized that deletion of Nrf2 would alter vasodilatory responses of coronary arterioles and limit exercise training‐induced adaptations of coronary vasodilatory function. We exercise trained wild type (WT) Sprague‐Dawley rats, and their littermates that were lacking the Nrf2 gene (Nrf2KO). Rats were either exercise trained (EX) on a motor‐driven treadmill 5 days/wk or remained sedentary (SED) in their cages for 10–12 weeks. A mixed moderate aerobic and high‐intensity interval training protocol was utilized. At the end of the training period, coronary arterioles were isolated and vasodilatory responses to intraluminal flow (pressure differences from 2–60 cm H2O) and the exogenous nitric oxide donor, Dea‐NONO‐ate (1×10−9–1×10−4M), were evaluated. Endothelium‐dependent vasodilation to intraluminal flow was not altered by either deletion of Nrf2 or by exercise training. In contrast, endotheliumin‐dependent vasodilation to Dea‐NONO‐ate, was reduced in coronary arterioles from Nrf2 rats as compared to arterioles from WT rats (WT vs Nrf2 KO; P=0.054). Exercise training increased responsiveness to Dea‐NONO‐ate in arterioles from WT rats (WT EX vs WT SED; P<0.05), but not in arterioles from Nrf2KO rats. These data suggest that deficiency of Nrf2 alters the function of vascular smooth muscle, but not the function of the vascular endothelium in coronary arterioles. Exercise training increases the vasodilatory responsiveness of coronary arteriolar smooth muscle to nitric oxide, but not in the absence of Nrf2, suggesting that mechanisms of redox homeostasis and nitric oxide signaling interact in the smooth muscle of coronary arterioles.

Support or Funding Information

NIH R15AG055029

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Selective disruption of IGF‐1 signaling in astrocytes up‐regulates soluble epoxide hydrolase and impairs EET‐mediated vasodilation
Authors: Kiss Tamas , Balasubramanian Priya , Tarantini Stefano , Fulop Gabor A , Yabluchanskiy Andriy , Csipo Tamas , Lipecz Agnes , Farkas Eszter , Sonntag William E , Csiszar Anna , Ungvari Zoltan
Published: June 2021

Insulin‐like growth factor 1 (IGF‐1) exerts multifaceted protective effects on the cerebral microcirculation and age‐related reduction of circulating IGF‐1 levels is known to promote cognitive decline. Astrocyte‐mediated neurovascular coupling (NVC), which adjusts cerebral blood flow to increased energy requirements of activated neurons, plays a critical role in the maintenance of normal neuronal function. Although previous studies demonstrate that circulating IGF‐1 deficiency significantly impairs NVC, the role of astrocyte‐specific effects of IGF‐1 in regulation of NVC is not completely understood. To test the hypothesis, that disruption of IGF‐1 signaling specifically in astrocytes impairs pathways involved in regulation of cerebral blood flow regulation we assessed changes in local cerebral blood flow elicited by contralateral whisker stimulation in mice with astrocyte‐specific knock‐down of IGF‐1 receptor 1 (Igfr1f/fGfap‐Cre), and respective controls using laser speckle contrast imaging. We found that NVC responses were significantly impaired in Igfr1f/fGfap‐Cre mice (4±1%) as compared to that in control mice (10±1%). In control mice NVC responses were significantly decreased by pharmacological inhibition of epoxyeicosatrienoic acid (EET) synthesis (MS‐PPOH) (4±1%). In contrast, NVC responses in Igfr1f/fGfap‐Cre were unaffected by MS‐PPOH. Analysis of expression of genes enriched in astrocytes that have function al relevance for CBF regulation revealed that in Igfr1f/fGfap‐Cre mice expression of soluble epoxy hydrolase was up‐regulated both at the mRNA and protein level. Pharmacological inhibition of soluble epoxy hydrolase improved NVC responses in Igfr1f/fGfap‐Cre mice. Collectively, our findings support the concept that normal astrocyte function is essential for the adequate NVC responses and provide evidence that decreased IGF‐1 input to astrocytes results in increased degradation of EETs. impairing functional hyperemia. We propose that these findings have relevance for the pathogenesis of cognitive decline associated with age‐related IGF‐1 deficiency.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
An Ex Vivo Model for Investigating Transplanted Pancreatic Islet Vascular Integration
Authors: Dolan Robert M , Hodges Nicholas A , Phelps Edward A , Murfee Walter L
Published: June 2021

Vascular integration of transplanted pancreatic islets is imperative for islet graft survival and treatment of type 1 diabetes. Despite only comprising 1–4% of the pancreas mass, islets receive 15% of the pancreatic blood flow, because the microvascular network within the islet is much denser than the surrounding exocrine tissue. We were motivated to better understand how islets influence local microvascular networks and how networks form connections with islets in experimental models that mimic the complex environment of real tissue. Recently, our laboratory established the rat mesentery culture model as a tool to investigate real‐time cell dynamics involved in microvascular growth. An advantage of the model is the ability to observe blood vessel, lymphatics and immune cells. The objective of this study is to establish the rat mesentery tissue culture model as a tool to investigate islet tissue integration. Islets harvested from Sprague Dawley rats were DiI labelled and seeded onto adult male Wistar rat mesentery tissue at an approximate density of 20 islets per tissue and then cultured in MEM with 1% PenStrep and 10% fetal bovine serum for 3 days. After culture, DiI positive islets remained intact. In avascular regions, radial lectin positive capillary sprouts with DiI labeling were observed to be forming from islets. In pre‐vascularized regions, lectin positive capillary sprouts around islets connected with capillaries from pre‐existing networks. Our results establish the rat mesentery culture model as a platform for tracking cell dynamics associated with islet transplantation.

Support or Funding Information

NIH R01AG049821

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dynamic Carotid Pressure‐Area Relation across the Adult Lifespan
Authors: Tarumi Takashi , Tomoto Tsubasa , Sugawara Jun
Published: June 2021

Carotid arterial stiffness is an established risk factor for cerebrovascular disease; however, its structural property in response to pressure pulsatility remains unclear. Therefore, we investigated the dynamic association between carotid artery pressure (CAP) and area (CAA) in healthy individuals across the adult lifespan.

Methods

108 participants (age range=19–85 years, 43% women) were tested. The CAA and CAP waveform were measured simultaneously from the bilateral common carotid arteries using applanation tonometry and ultrasonography respectively. To account for individual vessel size differences, CAA was normalized to the mean value and expressed in percentage. The CAP and CAA waveform were fast Fourier transformed to calculate power spectral densities (PSD), then transfer function analysis was used to estimate CAP‐CAA gain and coherence function.

Results

Older adults showed higher systolic and pulse pressure than younger adults. Systemic arterial stiffness, as assessed by brachial‐ankle pulse wave velocity, was also elevated in older adults. Spectral analysis revealed that PSD of CAP increases whereas that of CAD decreases with advancing age, and most of the age‐related differences are observed below ~4 Hz (Figure A). Furthermore, transfer function analysis exhibited the progressive reductions of CAP‐CAD gain in middle‐aged (0.264±0.087%/mmHg) and older adults (0.232±0.092%/mmHg) when compared with younger adults (0.414±0.166%/mmHg), while its coherence function remained at similar levels (Figure B).

Conclusions

The dynamic CAP‐CAA gain is significantly reduced in middle‐aged and older adults compared to young adults. These findings suggest that the structural property of the carotid artery is altered during middle age which may increase the risk of cerebrovascular disease incidence.

Support or Funding Information

This work was supported by JSPS KAKENHI 16KK0011 and 17H02186.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dietary Flaxseed Protects against Post‐Myocardial Infarction Arrhythmias and Injury
Authors: Parikh Mihir , Raj Pema , Austria J Alejandro , Yu Liping , Netticadan Thomas , Pierce Grant N.
Published: June 2021

Dietary Ω‐3 polyunsaturated fatty acids (Ω‐3 PUFAs) have been associated with a lower incidence of cardiovascular events and sudden cardiac death. Flaxseed is one of the richest plant sources of Ω‐3 PUFAs and has been observed to retard the progression and accelerate the regression of atherosclerotic plaque. The aim of the study was to examine the effects of dietary flaxseed on heart function and arrhythmias that develop after a myocardial infarction (MI). The left anterior descending coronary artery was ligated in rats to induce the MI. Rats were randomized into five groups: sham MI with normal chow, MI with normal chow, MI with 10% milled flaxseed supplementation (flax), MI with 4.4% supplemented flax oil rich in alpha‐linolenic acid (ALA), and MI with flax lignan secoisolariciresinol diglucoside (SDG) supplementation (0.44%). Animals were fed with their respective diets for two weeks before and for 8 weeks after the surgery. Echocardiography and continuous ECG recordings were obtained after ligation to confirm the induction of the MI, to check for arrhythmias and to assess cardiac function. Histological examination was also performed to evaluate cardiac fibrosis. Dietary supplementation with flax, ALA, and SDG significantly reduced the incidence of arrhythmia. Hearts obtained from flax, ALA, and SDG supplemented animals exhibited the smallest infarct size (12.39±0.77%, 13.70±1.20%, 11.63±1.36% vs. 34.02±3.22%, p<0.001). The left ventricle in the flax group was significantly less dilated compared to the control group (6.41±0.22 mm vs. 8.26±0.28 mm, p<0.001). A significantly small percentage of myocardial fibrosis and levels of tumor necrosis factor‐α were observed in all flax groups compared to the MI group (p<0.001). Together, this study generates evidence for a beneficial effect of flaxseed in patients post MI for the prevention of arrhythmias and ventricular remodeling.

Support or Funding Information

This work was supported by AAFC, CIHR, SaskFlax, Western Grain Research Foundation, Pizzey's Ingredients and St Boniface Hospital Foundation.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Gastrin Enhances the Sodium induced GLP‐1 secretion in the L‐Cells
Authors: Konkalmatt Prasad R , Asico Laureano D , Villar Van Anthony M , Cuevas Santiago , Armando Ines , Jose Pedro A
Published: June 2021

Organ‐to‐organ communication plays an important role in the regulation of fluid and electrolyte balance and blood pressure. The gastrointestinal tract and kidney are organs involved in this process. The concept that these two organs communicate with each other is not new but the details of their communication pathways are not well studied. We hypothesized that in response to sodium ingested, a sodium sensor in the stomach induces the secretion of gastrin from the G‐cells and glucagon‐like peptide‐1 (GLP‐1) from the L‐cells. These two hormones taken up by the renal proximal tubule from the circulation, in turn regulate renal sodium transport to maintain sodium balance and normal blood pressure. The germline deletion or stomach‐selective silencing of Gast, increased blood pressure in conscious Gast−/− BALB/c mice (125 ± 3 vs 141 ± 4 mm Hg: *P<0.05 t‐test, n=3–6/group), and impaired their ability to excrete an oral sodium load (0.69 mmol sodium/0.1kg body weight). Incubation of human G‐cells in a medium with a high sodium (170 mM) concentration increased the sodium channel activity, intracellular sodium, and gastrin protein expression by 1.9 ± 0.3‐fold, relative the incubation medium with145 mM sodium. The exposure of BALB/c mouse stomach to 0.56 or 0.84 mmol sodium/0.1 kg body weight, in the absence of food, increased gastrin expression in 30 min by 3.2 ± 0.8‐fold or 6.6 ± 0.75‐fold, respectively. L‐cells exposed to normal (145 mM) and high (170 mM) concentrations of sodium, but not to low sodium concentration (90 mM), increased GLP‐1 expression and induced GLP‐1 secretion in a concentration dependent‐manner. GLP‐1 secretion was 3.6 ± 0.6‐fold and 5.1 ± 0.8‐fold higher in L‐cells exposed for 4 hours to normal and high sodium respectively, compared with L‐cells exposed to low sodium. Moreover, gastrin (1 mM), enhanced the high sodium‐induced GLP‐1 secretion by 22% ± 1.9, but had no effect on the low or normal sodium‐induced GLP‐1 secretion. Immunoblot analyses showed that the exposure of L‐cells to normal sodium did not change gastrin expression but exposure to high sodium increased gastrin expression by 1.56 ± 0.2‐fold compared with L‐cells exposed to low sodium concentration. These results indicate that sodium‐induced gastrin and GLP‐1 secretion and expression may play a key role in the regulation of sodium balance and blood pressure.

Support or Funding Information

National Kidney Foundation NKF‐MD‐Mini and US National Institute of Health, R56DK116828, R37HL023081, P01HL074940, R01HL092196, R01DK039308, and R01DK090918.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Stress Response of Salivary Chromogranin A and Non‐Invasive Sympathetic Activity Monitoring by Wavelet Transform Analysis in Hypertensive Subjects
Authors: Yajima Yoshiharu , Mitsubayashi Hiromi
Published: June 2021

Background

Stress is one of the risk factor in cardiovascular disease. However, stress induced cardiovascular response is very difficult to estimate because those response are varied in each individuals. A stress marker, salivary chromogranin A, is considered to be a useful tool for patients without any painful stress such as sampling blood test. Furthermore, this method is ease to sampling by any kind of paramedical staffs. We try to estimate the stress induced cardiovascular response both mental stress and physical stress by using salivary chromogranin A.

Method

Total 18 adults (30 to 65 years old), 9 of essential hypertensive patients and 9 of healthy or non‐hypertensive cardiovascular disease patient were recruited in a local clinical hospital as volunteer measured salivary chromogranin A and change in blood pressure and heart rate induced by mental arithmetic stress or handgrip physical stress, using tonometry blood pressure measurement devise and electrocardiogram those data were collected to laptop computer recording and analyze for sympathetic nerve activity index and parasympathetic nerve activity index by wavelet transform analysis software, simultaneously.

Results

Although personal stress level were different in each individual, 61% of subjects increase salivary chromogranin A and increase blood pressure and heart rate after mental arithmetic stress.

Conclusion

Salivary chromogranin A could be useful biomarker for detecting stress sensitive individuals without painful blood sampling, which may be helpful to detect stress sensitivity in clinical patients to prevent cardiovascular events.

Support or Funding Information

none.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Deletion of the 20‐HETE receptor (GPR75) impairs myogenic tone of renal preglomerular arteries
Authors: Morelli Marco Bruno , Gilani Ankit , Agostinucci Kevin , Zhang Frank , Garcia Victor , Schwartzman Michal L.
Published: June 2021

20‐Hydroxyeicosatetraenoic acid (20‐HETE), one of the principal cytochrome P450 (CYP)‐derived eicosanoids, is a potent vasoactive lipid whose vascular effects include stimulation of smooth muscle contractility, migration and proliferation, as well as endothelial cell dysfunction and inflammation. Increased levels of 20‐HETE in experimental animals and in humans are associated with hypertension, stroke, myocardial infarction and vascular diseases. We recently identified GPR75, an orphan G‐protein (Gaq/11) coupled receptor (GPCR), as a specific cellular target to which 20‐HETE binds and through which it activates a signaling cascade that culminates in many of the functional outcomes attributed to 20‐HETE in vitro and in vivo (Garcia et al, Circ. Res., 2017). To further establish the role of GPR75 as a 20‐HETE target for its bioactions, global GPR75 knockout (Gpr75−/−) mice were generated. A breeding colony of Gpr75+/−XGpr75+/− has been established and experiments were conducted to assert the genotype and assess whether a basic phenotype exists. Levels GPR75 mRNA were undetectable in brain, liver, heart, aorta and kidney from Gpr75−/− mice. Levels of Gpr75 mRNA in liver, heart and aorta tissues from Gpr75+/− (HET) was lower compared to littermate Gpr75+/+ (WT) mice. The initial phenotypic characterization showed no differences between WT and transgenic mice in body weight or systolic blood pressure (93±4, 89±5 and 88±6 mmHg in male and female WT, Gpr75+/− and Gpr75−/− mice, respectively). There were no significant gender differences in body weight or blood pressure. Since 20‐HETE has been shown to promote vasoconstriction, increase vascular reactivity and contribute to the myogenic response in renal and cerebral microvessels, we assessed whether deficiencies in GPR75 affects myogenic response in preglomerular arterioles (~50–80 μm). The myogenic response was markedly impaired in arteries from Gpr75−/− mice as internal diameter increased in response to increasing pressure and in response to 100 mmHg, internal diameter of arteries from Gpr75−/− and Gpr75+/− mice was 119.5±1.22 and 101.7±3.1 μm, respectively, as compared to 80.3±3.4 μm in arteries from WT (p<0.05). These results, together with our finding that in vascular smooth muscle cells 20‐HETE‐GPR75 pairing leads to inhibition of the BKca channels and increases in intracellular calcium concentration which contribute to vasoconstriction, suggest that deficiency in the expression of GPR75 mediates the impaired myogenic response because 20‐HETE is lacking its cellular target.

Support or Funding Information

Supported by NIH grant HL139793 and Regeneron Pharmaceuticals Inc.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Beetroot Juice Supplementation Did Not Change Exercise Capacity and Physical Function and Had Minimal Effects on Blood Pressure of Breast Cancer Survivors
Authors: Lima Natalia A , Gaspari Arthur Fernandes , Abbott Heather Ann , Finch Alfred Earl
Published: June 2021

Beetroot juice (BRJ) supplementation has been used as an ergogenic aid to improve exercise capacity and functionality in healthy and clinical populations. Positive effects such as improved blood pressure and blood flow have been demonstrated after the ingestion of BRJ in subjects with peripheral artery diseases and chronic obstructive pulmonary disease. Cancer treatment has detrimental lifelong effects on physical function and exercise capacity of survivors. Whether BRJ is an effective ergogenic aid in breast cancer survivors is unknown.

Methods

Twelve female breast cancer survivors (>40 years old) were recruited. All subjects were provided BRJ and placebo (PL) during two testing sessions visits in a randomized, crossover, double blind study design. Exercise capacity was assessed using the 400‐m walk test, while functional capacity was assessed using: timed up and go, five repetitions seat rise to stand, maximal voluntary contraction handgrip strength, rhythmic handgrip test (40% of MVC until fatigue), 6‐m backward walk, and 6‐m forward walk. Peripheral systolic and diastolic blood pressure and heart rate were collected pre‐ and post‐ both testing sessions. At the same time measurements arterial stiffness was assessed using applanation tonometry in the radial artery for pulse wave analysis (PWA).

Results

BRJ supplementation showed no significant statistical significance in any of the measured variables.

Conclusion

The results suggest that BRJ might not be an effective ergogenic aid for improving functional capacity in breast cancer survivors.

Variables
BRJ
PL
p

Exercise Capacity

400‐m walk (s)
284.7 ± 47.68
279.09 ± 50.95
0.45

Functional Performance

TUG (s)
6.05 (2.96)
6.05 (2.02)
0.07

Repeated chair stands (s)
9.12 ± 1.63
9.39 ± 1.57
0.5

MVC
17.7 (5.68)
16.07 (2.25)
0.81

Rhythmic Handgrip
199 (164)
191 (256)
0.26

6‐m backward walk (s)
14.22 ± 6.52
15.40 ± 5.82
0.35

6‐m fast walk (s)
3.07 (0.97)
3.53 (1.01)
0.94

TUG, timed up and go; MVC, maximal voluntary contraction.

BRJ
PL
ANOVA/Friedman

Pre
Post
Pre
Post
p values

HR
74 ± 14
99 ± 26
74 ± 11
100 ± 22
0.89

SBP
125 ± 14
141 ± 20
121 ± 15
147 ± 20
0.08

DBP
78 (10)
80 (14)
78 (9)
80 (7)
0.49

PWA

SBP
115 ± 13
129 ± 20
113 ± 14
134 ± 18
0.15

DBP
79 (10)
81 (17)
80 (10)
82 (8)
0.35

MP
93 ± 10
100 ± 14
95 ± 11
104 ± 10
0.35

PP
39 (13)
53 (17)*
35 (11)
47 (15)*
0.001

Aix
30 ± 12
33 ± 11
31 ± 11
39 ± 10
0.13

HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; MP, mean pressure; PP, pulse pressure; Aix, augmentation index.

p < 0.05

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Machine learning predictions of depression from time spent in cadence bands
Authors: Forrester Jenna , Thomas Diana , Adams Bryan , Stice Eric , Arigo Danielle , Scioletti Michael , Tudor‐Locke Catrine
Published: June 2021

Background

Depression impairs normal human functionality and can cause severe interruptions of normal everyday activities affecting productivity at work and at home. Physical activity is often proposed as an effective treatment for depression, however the relationship between physical activity and depression has not been evaluated with unsupervised machine learning algorithms. Unsupervised machine learning algorithms determine relationships between all variables without requiring user input information on which variables should be explanatory.

Methods

The National Health and Nutrition Examination Survey 2005–2006 (NHANES) dataset, which includes demographic characteristics, depression scores from the Patient Health Questionnaire (PHQ‐9), and 2‐weeks of accelerometer‐determined step data collected from 4,000 participants. Movement intensity using peak 30‐minute cadence (an index of best natural effort). Total movement volume was retained as steps/day. Linear and logistic regression techniques were employed to predict depression. We also performed a k‐means cluster and principal component analysis to identify those predictors that contributed most to depression variance.

Results

The linear regression model revealed that an increase of one unit of peak 30‐min cadence predicts a decrease in sum of the depression scores by 0.03 units. Similarly, logistic regression indicated that an increase in peak 30‐min cadence by 20 units predicted a 1.5 times decrease in depression. The k‐means cluster analysis resulted in 4 distinct clusters. In clusters 1,2,3 and 4, 5.0%, 7.9%, 6.0% and 6.5% were categorized as depressed respectively. Cluster 2 represented the most sedentary cluster.

Conclusions

Machine learning models combined with rich accelerometer data can be used to rigorously quantify the relationship between step‐defined physical activity and depression. These models can personalize physical activity treatment recommendations f for depression in terms of steps/d and peak 30‐minute cadence.

Support or Funding Information

None

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in liver perilipin gene expression during an oral lipid load in obese OLETF rats
Authors: Godoy‐Lugo Jose Arquimides
Published: June 2021

Non‐alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver maladies in the US. NAFLD is associated with obesity, hyperlipidemia, hypertension, insulin resistance, and diabetes; all traits linked to metabolic syndrome, affecting 20% of the US population. Inappropriate hepatic lipid accumulation is associated with metabolic syndrome. Intracellular lipid storage is regulated by lipid droplets (LDs) that are active components of the cell. LDs have surface proteins of which the most studied belong to the PAT family (Perilipin1–5), which participate in storage and lipid metabolism. To evaluate the effect that a high‐lipid load on the expression and dynamics of hepatic perilipins during early onset T2D, an oral fat tolerance test (OFTT) was performed in 28 wk‐old rats (n=5–6/group): (1) healthy, strain control LETO, and (2) obese, diabetic OLETF. Liver and blood were collected before (T0) and after (T1, T2, T4, and T8 hours) the lipid challenge. An acute increase in serum TG was observed at T2 (p= < 0.0001) and was maintained over the next 6 hours in OLETF whereas in LETO it decreased after the T2 mark. The mRNA expression of Plin2 increased 2.5‐fold in OLETF at T2 compared to LETO, and increased 2.5‐fold at T8 in LETO compared to baseline. Plin3 remained higher (p= 0.0077) in LETO compared to OLETF at T8. Plin4 did not change significantly in response to the lipid challenge between groups. Plin5 increased 1.8‐fold in LETO at T8 compared to baseline. These changes help explain the contributions of LDs to the regulation of hepatic lipids during both normal and diabetic conditions in response to a high lipid challenge similar to the consumption of a high‐fat meal. As Plin2 and 3 have been described as structural LD‐associated proteins, being present mostly in nascent LD, suggesting that a high fat load induces an acute induction of hepatocyte lipid storage. The increase in Plin5 suggests that lipid metabolism pathways are being activated, as Plin5 has been related with mitochondrial FA metabolism. The differential expression patterns of perilipins in response to an acute lipid challenge illustrates the timing of the cellular changes during the development of hepatic steatosis, providing useful insights into future development of treatment by targeting the PAT family of proteins.

Support or Funding Information

This work was supported by NIH's MHRT program.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelin Receptor‐dependent Responses in Overweight/Obese Postmenopausal Women
Authors: Nathaniel Sangeetha , Kuczmarski Andrew , Pollock David M , Wenner Megan M
Published: June 2021

Age‐related weight gain is greater in women compared to men, such that postmenopausal women are more likely to be overweight or obese (OW/Ob). Previous studies have demonstrated that OW/Ob older adults have impaired endothelial function in part due to endothelin‐1 mediated vasoconstriction via the ETA receptor. In addition, our laboratory has recently demonstrated an important role for ETB receptors and its contribution to vascular endothelial dysfunction in postmenopausal women.

PURPOSE

The purpose of this study was to test the hypothesis that ETB and ETA receptors contribute to impaired vasodilatory function in OW/Ob postmenopausal women.

METHODS

Fourteen postmenopausal women have completed the study: 8 normal weight (NW; 57±5 years, 22±2 kg/m2) and 6 OW/Ob (57±8 years, 28±3 kg/m2). We measured vasodilatory responses to local heating of the skin (laser Doppler flowmetry) during microdialysis perfusions of lactated Ringer's (Control), ETB receptor blockade (BQ‐788, 300nM), and ETA receptor blockade (BQ‐123, 500 nM). Cutaneous vascular conductance (CVC) was calculated during the plateau phase of local heating (42°C), and normalized to maximal vasodilation achieved by perfusion of sodium nitroprusside (28mM) and heating to 43°C. A two‐way ANOVA with post hoc Bonferroni correction was performed to compare the impact of weight on vascular responses to ETA and ETB mediated vasodilation compared to control. Data are presented as mean ± standard deviation.

RESULTS

ETB receptor blockade increased vasodilation in NW women (Control: 88±4 vs. BQ‐788: 94±4 %CVC max; P=0.03), whereas ETA receptor blockade did not significantly alter vasodilation (BQ‐123: 88±3 %max CVC; P>0.90 vs. Control). In OW/Ob, both ETB and ETA blockade increased vasodilation (Control: 89±4 vs. BQ‐788: 95±4, BQ‐123: 94±5 %max CVC; P<0.05). Furthermore, the vasodilatory response to ETA receptor blockade was greater in OW/Ob compared to NW (P=0.03).

CONCLUSION

These preliminary data suggest that while blockade of ETB receptors improves vasodilatory function in postmenopausal women, there is a larger contribution of ETA receptors impacting endothelial function in OW/Ob postmenopausal women.

Support or Funding Information

Supported by: NIH GRANT P20 GM 113125 and AHA 16SDG30700015

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Protective Effects of Calcitriol Against Fructose‐induced Hyperglycaemia and Dyslipidaemia in Male Albino Wistar Rats
Authors: Sadau Yakubu , Lai Ibrahim , Gari Fatima Umar Mai
Published: June 2021

Hyperglycemia and lipidaemia have been found to produce adverse metabolic alterations in glucose and lipid metabolism. The study investigates the preventive role of calcitriol supplementation on fructose‐induced hyperglycaemia and dyslipidaemia in fructose‐drinking Albino Wistar rats. Twenty five male Albino rats were used. The rats were divided into 5 groups of 5 animals each. Group I: Control; received normal rat feed + distilled water, Group II: Received normal rat feed + 125 μg/kg of Calcitriol (CTR), Group III: Received normal rat feed + 10% fructose solution (FDR), Group IV: Received normal rat feed + 10% fructose solution (FDR) + 0.3 mg/kg of glibenclamide (GLIB). Group V: Received normal rat feed + 10% fructose solution (FDR) + 125 μg/kg of Calcitriol (CTR). For the induction of hyperglycaemia and lipidaemia rats were given 10% fructose solution as drinking water for eight weeks. The levels of fasting sugar and HbA1c were measured. Changes in body weights and lipid profile of rats were determined. CTR group exhibited no significant change in plasma glucose levels, HbA1c and body weights when compared to the control. In FDR group fasting sugar levels, glycated haemoglobin (HbA1c) and weights were found to be significantly increased compared group I. Glibenclamide administration in GLIB + FDR group effectively abolished the fructose‐induced hyperglycaemia and glycated haemoglobin in rats when compared to FDR group. In FDR + CTR group calcitriol supplementation successfully blocked and prevented the fructose‐induced increased in fasting sugar, HbA1c levels and weight in rats when compared with FDR group. CTR group exhibited no significant changes in lipid profile parameters compared control. FDR exhibited a significant increase in serum total cholesterol, when compared to control group. Similarly, fructose feeding resulted in a significant elevation in triglycerides levels in comparison to the control rats. FDR group rats had elevated levels of LDL‐C which was significant when compared with the control group. Although, high density lipoprotein cholesterol was increased in FDR group, the increased was not significant and the result was comparable to that of the control. In FDR + CTR group, oral calcitriol supplementation potentially prevented fructose in inducing alterations in serum lipid profiles when compared to FDR group. The result showed that calcitriol supplemention infructose‐drinking rats protects against hyperglycaemia and dyslipidaemia.

Support or Funding Information

Funding is through the Tertiary Education Trust Fund, Nigeria. When an acceptance and invitation letter is forwarded to the Fund atleast 3 months before the conference time

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Dynamic Eccentric Leg Exercise Training on Functional Fitness and Arterial Stiffness in Older Adults
Authors: Durocher John J. , LewAllen Sarah E. , Maanika Carley B. , Elmer Steven J. , Rajeshkumar Lavanya , Trewartha Kevin M.
Published: June 2021

Eccentric exercise is shown to offer musculoskeletal benefits in multiple populations, but little is known about the effect of chronic dynamic eccentric exercise training in older adults concerning functional physical fitness and cardiovascular health. Therefore, the purpose of this study was to determine if twelve weeks of dynamic eccentric leg exercise (Eccentron) could improve functional fitness and reduce arterial stiffness. Thirteen older adults (ages 65–79 years; M = 70±1) performed dynamic eccentric leg exercise twice per week at a light to somewhat hard rating of perceived exertion. Exercise duration increased from five minutes per session in the first week to 25 minutes per session during the final week. Timed up and go test significantly improved from pre‐ to post‐training (5.7±0.2 vs. 5.3±0.1 s; p<0.05). Likewise, Berg Balance Score was statistically (p<0.05) improved from pre‐ to post‐training. Participants demonstrated non‐significant increases in single‐leg knee extensor strength (43.0±2.6 vs. 45.2±2.8 kg; p=0.26). Aortic arterial stiffness, assessed via carotid‐femoral pulse wave velocity, did not change from pre‐ to post‐eccentric exercise training (8.6±0.7 vs. 9.2±0.5 m/s; p=0.44). Similarly, leg arterial stiffness, assessed as femoral to dorsalis pedis pulse wave velocity, was unchanged (9.9±0.8 vs. 9.2±0.5 m/s; p=0.31). Our results demonstrate how 12‐weeks of eccentric training can positively influence functional physical fitness measures in older adults without a negative influence on arterial stiffness. Significant improvements in timed up and go and the Berg Balance Score, and non‐significant increases in leg extensor strength, suggests that older adults could improve their agility and balance, and reduce their risk of falling through eccentric leg exercise.

Support or Funding Information

Supported by the Portage Health Foundation and Michigan Tech Research Excellence Fund.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chronic Nicotine Inhalation Promotes the Development of Pulmonary Hypertension
Authors: Yue Xinping , Oakes Joshua M , Xu Jiaxi , Lazartigues Eric , Gardner Jason D
Published: June 2021

Pulmonary hypertension is a condition of increased blood pressure within the arteries of the lungs, leading to clinical symptoms including shortness of breath, syncope, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The exact cause of pulmonary hypertension is often unknown, but the risk factors include a family history, prior blood clots in the lungs, HIV/AIDS, cocaine use, and smoking. Nicotine is the addictive component of tobacco products including conventional cigarette, cigar, and the increasingly popular electronic cigarette (e‐cigarette). The purpose of this study was to examine the effects of chronic nicotine inhalation in the development of pulmonary hypertension. C57BL/6 mice (male, 8–12 weeks of age) were exposed to air (control) or nicotine vapor (daily, 12 hour on/12 hour off) for 8 weeks. Nicotine exposure was assessed by weekly measurement of serum cotinine levels (a more stable metabolite of nicotine), which showed a weekly average of 599.0 ± 54.28 ng/ml (mean ± SEM) in nicotine exposed mice. As the positive control, a subset of air‐exposed control mice were subjected to Angiotensin‐II (Ang‐II) infusion through subcutaneous osmotic mini‐pumps (450 ng/kg/min) for the last 4 weeks. At the end of the 8 weeks, mice were subjected to right heart catheterization (Millar SPR‐1000 Mikro‐Tip mouse pressure catheter) to measure the right ventricular systolic pressure (RVSP) followed by tissue collection. Nicotine exposed mice exhibited significantly increased RVSP (39.57 ± 4.17 mmHg, n=7) compared to the air‐exposed controls (22.31 ± 1.70 mmHg, n=8, P < 0.01 by unpaired student t‐test). Interestingly, the increase in RVSP by nicotine was as potent as Ang‐II infusion (38.00 ± 2.18 mmHg, n=7, P < 0.001 vs. air controls). Furthermore, our discovery quantitative proteomic analysis identified atrial natriuretic peptide receptor 1 and periostin among the over‐expressed proteins in the lungs from nicotine exposed mice compared to the air controls, both of which have been shown to be involved in the regulation of pulmonary blood pressure. We conclude that chronic nicotine inhalation promotes the development of pulmonary hypertension. In addition, to the immediate relevance to public health, our data suggest that nicotine users, especially young adults with e‐cigarette use, are at elevated risk for the development of pulmonary hypertension. Ongoing experiments are focusing on the mechanisms of nicotine‐induced pulmonary hypertension, including nicotine‐induced pulmonary vascular remodeling.

Support or Funding Information

This work was supported by the National Heart, Lung, and Blood Institute R01 HL135635 and the National Institute of General Medical Sciences P30 GM106392.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Dietary Salt Intake Exaggerates Arterial Blood Pressure during Exercise in healthy Normotensive Adults
Authors: Hammond Stephen , Caldwell Jacob , Banister Heather R , Lovoy Garrett M , Post Hunter K , Sutterfield Shelbi L , Ade Carl J
Published: June 2021

High dietary salt intake is associated with an increased risk for the development of hypertension, cardiovascular (CVD) and cerebrovascular disease. Additionally, exaggerated blood pressure during dynamic exercise is independently predictive of future CVD beyond resting blood pressure and other conventional risk factors. This is critical given that in animal models, dietary salt negatively augments blood pressure responses during static hind‐limb contractions, suggesting an increased risk of an adverse CVD event during exercise with high dietary salt. However, it currently remains unknown if high salt intake increases arterial blood pressure and impairs vascular function during voluntary dynamic exercise in healthy men and women. Based on previous preclinical reports, we hypothesized that high salt intake would decrease resting vascular endothelial function, increase arterial blood pressure during dynamic exercise and decrease functional sympatholysis. Thirteen healthy men and women underwent a randomized, double‐blind, placebo‐controlled trial for 7 days with either 15g/day sodium chloride supplement or cellulose. Beat‐by‐beat mean (MAP), systolic (SBP) and diastolic (DBP) were recorded throughout the trial on the non‐exercising limb. Forearm blood flow (FBF) was calculated via mean blood velocity derived from ultrasonography on the brachial artery of the exercising limb. All patients performed a flow‐mediated dilation (FMD) protocol followed by (20% maximal voluntary contraction) submaximal hand‐grip exercise for 7 min with lower‐body negative pressure initiated during min 5 – 7. FMD was significantly reduced during the HS condition (HS: 2.2±0.26e−5; Pl: 4.1±0.56e−5; p<0.01). Compared to placebo, the absolute steady‐state exercise MAP and SBP were significantly higher during HS compared to the placebo condition (p<0.05). However, functional sympatholysis was not different between conditions (p=0.07). In summary, the results of this study show the effects of HS intake on arterial blood pressure during handgrip exercise. These findings highlight that the augmented exercise blood pressures may be key mediator for the increased risk for adverse CVD outcomes associated with high dietary salt intake.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.