bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Foreskin Fibroblast Behavior in the Presence of 3D Collagen, Fibrin, and Calcium Phosphate
Authors: Eckhart Kyle , Kniseley Atherton , Bucci Brianna , Vaghasia Nikita , Tawil Bill
Published: June 2021

3D modeling in cell‐based assays, provides an environment that mimics in vivo conditions. This allows for the examination of innate cellular behavior and aids in the development of next‐generation modeling and therapies. Cellular environments can be modeled using various constituents to manipulate the rigidity, porosity, and size of various 3D environments to observe cell characteristics in an environment similar to that from which they originated. The proliferation of Human Foreskin Fibroblasts (HFF‐1) were examined in a 3D collagen matrix with varying cell densities. Higher cell concentration within the 3D collagen matrix showed lower HFF‐1 cell proliferation. Furthermore, fibrin clots were used to mimic 3D microenvironments because of its biocompatibility and controllable biodegradability. Changing fibrinogen and thrombin concentrations provides a varying effect on the rigidity and porosity of a 3D environment and therefore affects the overall behavior of HFF‐1. There was an increase in fibrin bead size in the presence of cells with higher concentrations of fibrinogen and thrombin. To mimic a bone microenvironment, calcium phosphate (CaP) was introduced in increasing concentrations to support a rigid and structured environment. Increasing concentrations of CaP, resulted in an increase in the initial adhesion and a decrease in HFF‐1 proliferation over a 7‐day incubation period. Overall, cells in a 2D environment behave different than those in a 3D environment with varying components to imitate their in vivo conditions.

Support or Funding Information

N/A

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cytokine Responses to Cyclical Blood Flow Restriction Exercise
Authors: Sprick Justin , Romero Steven , Rickards Caroline
Published: June 2021

Introduction

We developed a novel adaptation of blood flow restriction exercise, cyclical blood flow restriction exercise (C‐BFRE), as a method to potentially augment the cardio‐protective effects associated with conventional exercise (CE) and remote ischemic preconditioning (RIPC). As the cytokines IL‐6 and IL‐10 have been implicated in mediating the acute cardio‐protection associated with both exercise training and RIPC when performed independently, we hypothesized that C‐BFRE would augment the systemic release of these factors compared to an acute bout of either CE or RIPC alone.

Methods

13 young healthy subjects (6M/7F, age 28±2 y) completed 3 experimental sessions separated by at least 1 month each. Aerobic exercise was performed via 40‐min of treadmill walking at 65–70% HRmax with (C‐BFRE) and without (CE) application of bilateral thigh cuffs inflated to 220 mmHg (4 × 5‐min inflation periods followed by 5‐min reperfusion periods). RIPC consisted of 4 × 5‐min thigh cuff inflation periods (220 mmHg) followed by 5‐min reperfusion periods in the absence of exercise. Venous blood samples (via an antecubital vein) were collected at baseline and immediately following completion of each protocol for analysis of IL‐6 and IL‐10 via multiplex ELISA.

Results

Plasma IL‐6 increased from baseline following CE (Pre, 0.26 ± 0.03 vs. Post, 0.40 ± 0.07 pg/ml; P=0.03) but not with C‐BFRE (Pre, 0.28 ± 0.05 vs. Post, 0.34 ± 0.07 pg/ml; P=0.75) or RIPC (Pre, 0.31 ± 0.04 vs. Post, 0.32 ± 0.03 pg/ml; P=1.0). There were no changes in plasma IL‐10 from pre‐ to post‐intervention for any of the three conditions (P=0.42 for main effect of time).

Discussion

Contrary to our hypothesis, we observed no change in plasma IL‐10 or IL‐6 with application of acute C‐BFRE. These findings suggest that the model of C‐BFRE utilized in this study does not augment the release of these cytokines in young healthy individuals. This may be due to the timing of the blood samples, the use of a standard occlusive pressure across all subjects, and the young, healthy subjects tested in this study. Future work should delineate the inflammatory response induced by C‐BFRE at more extended recovery time points, with use of individualized occlusive pressures, and in more clinically relevant populations in both acute and long term settings.

Support or Funding Information

Funding for this study was provided, in part, by training fellowships awarded to Justin Sprick through a NIH‐supported Neurobiology of Aging Training Grant (T32 AG020494, PI: Singh, M), and a Ruth L. Kirchstein NRSA F31 Predoctoral Fellowship (1F31HL134242‐01A1; PI: Sprick, JD), a UNTHSC Faculty Research Pilot Grant (PI: Rickards, CA), and a Texas Chapter of the American College of Sports Medicine (TACSM) Student Research Development Award (PI: Sprick, JD).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effect of Age and Acute Exercise on Circulating Endostatin
Authors: Temperley McKenzie K. , Mardis Benjamin R. , Iwamoto Erika , Bock Joshua M , Casey Darren P. , Luttrell Meredith
Published: June 2021

BACKGROUND

Endostatin may have both angiogenic and angiostatic effects in vivo, although angiostatic effects appear to predominate. It has been reported that circulating levels of endostatin increase after acute exercise in young adults; however, it is unclear whether healthy older adults exhibit a similar response.

PURPOSE

The purpose of this study was to determine the effect of age on changes in serum endostatin concentration following an acute bout of dynamic exercise.

METHODS

Ten young (25 ± 1 years, 5M/5F) and nine older (68 ± 2 years, 4M, 5F) healthy but sedentary to recreationally active adults completed a single 45‐minute bout of submaximal cycle ergometer exercise at 60 – 65% of their age‐predicted maximal heart rate. Venous blood samples were obtained prior to (PREX), immediately post‐ (POSTX0), and at three hours post‐exercise (POSTX3). Serum concentrations of endostatin were analyzed at each time point using an enzyme‐linked immunosorbent assay. Absolute protein concentrations at each time point and fold‐change from PREX concentrations are reported.

RESULTS

There was no difference in PREX serum endostatin concentration between young (136.2 ± 18.48 pg/mL) and older adults (125.9 ± 11.48 pg/mL) (p=0.81). Additionally, there was no age effect on absolute endostatin concentrations at POSTX0 and POSTX3 (p = 0.06 for interaction). However, when comparing the fold‐change in endostatin concentration after exercise, there was a significant interaction (p = 0.01) between age and POSTX0 to POSTX3 time point. The main effects (time, age) were not significant. Simple main effects analysis revealed a difference in fold‐change in concentration of endostatin from PREX in older (p = 0.02) but not younger (p = 0.80) adults from POSTX0 to POSTX3.

CONCLUSIONS

Our data suggests there is no difference in either PREX serum endostatin concentrations between young and older adults. However, older adults may have a different temporal response in serum endostatin following a single bout of moderate intensity dynamic exercise compared to young adults.

Support or Funding Information

Research Support: University of Iowa Carver College of Medicine FUTURE in Biomedicine Program (MJL, BRM, DPC).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Aerobic Exercise and Environmental Heat Stress as Adjuvants to Seasonal Influenza Vaccine
Authors: Colburn Abigail , Wright Skylar , Lopez Virgilio , Giersch Gabrielle , Belval Luke , Hosokawa Yuri , Huggins Robert A , Armstrong Lawrence , Casa Douglas J , Lee Elaine C
Published: June 2021

Influenza strain diversity and variability and individual immune health contribute to reduced vaccine efficacy. Among adjuvants that enhance vaccine effectiveness, several studies have examined the relationship between acute exercise stress and influenza vaccination immune responses in humans. It is proposed that acute bouts of stress enhance immune response, but optimal intervention, timing of intervention, and mechanisms have yet to be identified. As Toll‐like receptor (TLR) agonists enhance innate immune responses and support development of chronic humoral responses, exercise induced release of the TLR4 ligand lipopolysaccharide (LPS) into circulation may be a mechanism for benefit of pre‐vaccine exercise. This study aimed to assess the effects of exercise and exercise‐heat stress completed before seasonal influenza vaccination (IV) on short‐ and long‐term immune responses. Thirty‐four males (body mass, 77.41±12.48kg; age, 21.5±4.4y; maximal aerobic capacity (VO2max), 43.53±8.24mL/kg/min) were randomized into 1 of 3 groups: no exercise (NE, n=12) or 60 minutes of 60%VO2max exercise with (MEH, n=11) or without (ME, n=11) environmental heat stress. Exercise and baseline blood samples were completed 25.11±5.92h before IV, and subsequent blood samples were collected 23.45±6.13h, 13.06±2.96d, and 29.54±3.73d following IV. Exercise environmental conditions were different between ME and MEH, respectively (average wet bulb globe temperature, 32.91±2.67°C, 41.21±2.88°C; p<0.001), but physiological stress was similar (average rectal temperature, 37.30±0.48°C, 27.61±1.36°C, p=0.513; heart rate, 114±105bpm, 118±105bpm, p=0.103) due to controlled exercise intensity. On‐going research will utilize hemagglutinin inhibition, cortisol, and LPS assays to quantify virus‐specific antibody responses, stress, and TLR4 activation respectively. Understanding innate and humoral responses will elucidate the potential of exercise and exercise‐heat stressors as adjuvants for IV.

Support or Funding Information

New investigator start‐up, InCHIP Interdisciplinary Seed Grant

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Perceptual Responses to Exercise Heat‐Stress in Smokers versus Non‐Smokers
Authors: Kennedy Kallean Joan , Caldwell Aaron , Garcia Nathanael , Upton Martha , Hartzell Kristen , Ganio Matthew
Published: June 2021

Physiological and psychological/mental stress occurs as individuals undergo exercise‐ heat stress. The latter can include perceptual measures, feelings of mood, and cognition performance. Decrements in these may lead to a decrease in productivity and motivation. Prior work suggests that smokers and non‐smokers have physiological differences, thus it is possible that smokers perceive exercise heat‐stress differently. It is important to understand how smokers “feel” during heat stress, especially when they are being physically active.

Purpose

The purpose of this pilot study was to determine whether exercise heat stress has negative cognitive and perceptual effects on smokers versus non‐smokers.

Methods

Three current male smokers (SMK: 20.6 ± 2.3 yr; 6 ± 1.7 cigarettes/day; 86.6 ± 10.2 kg; 21 ± 3.1% body fat) and 3 non‐smokers (N‐SMK: 24.6 ± 5.1 yr; 80.3 ± 3.6kg; 20.7 ± 8.2% body fat) participated in an experimental trial consisting of subjects performing 60 total minutes of cycling. Specifically, there were three 20‐minute exercise periods with two 20 minute rest periods in between each exercise bout. Participants cycled at a target metabolic heat production of 6 watts/kg in an environmental chamber at 40°C, 35 % relative humidity. The subject's internal temperature (Trec ) via rectal thermistor, mean body temperature (Tbody), heart rate and perceptual measures were collected every 5 and 15 minutes throughout each exercise and rest periods. Perceptual measures included perceived exertion, thirst, thermal sensation, muscle pain, motivation to continue, feeling and comfort.

Results

During the experimental trial, Trec at baseline for SMK and N‐SMK was 37.36±0.15 and 37.43±0.7°C, respectively; at the end of exercise (i.e., min 60) Trec was 38.03±0.2 and 38.34±0.7°C. Tbody for SMK and N‐SMK at the end of exercise was 39.5±0.16 and 39.7±0.7°C, respectively. HR was similar in SMK (132 ± 16.7 bpm) vs. N‐SMK (133±19.1 bpm). At the end of the last exercise bout the final perceptual ratings for SMK and N‐SMK were 10±3 and 11±1 for RPE, 4±2 and 4±3 for Thirst, 4.7±0.6 and 5.6±0.3 for Thermal, 1.3±0.6 and 1.2±0.8 for Muscle Pain, 4±2 and 4±1 for motivation to continue, 3±2 and 2±1 and for feeling and 2±1 and 2±1 for comfort.

Conclusion

In this pilot study, when exercising at a similar relative rate of metabolic heat production, smokers had similar physiological responses. Likewise, the perceptual variables obtained were also similar between smokers and non‐smokers. This has implications for occupational settings in which smokers are heat stressed and trying to complete tasks that involve cognitive thought processes.

Support or Funding Information

Funding provided by: Arkansas Department of Higher Education and the University of Arkansas

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Caffeine and Menstrual Phase on Performance of Female Athletes during Heat Stress
Authors: Rutherford Maura McLean , Palmer Matthew S
Published: June 2021

The effects of menstrual phase on athletic performance are controversial, but commonly ascribed to temperature‐related impairments in physical and cognitive performances. Caffeine stimulates the CNS to enhance endurance performance, and while effects persist for men exercising in the heat, little work has been done with women. Moreover, many female athletes use oral contraceptive steroids (OCS) to regulate their menstrual cycles, which may pronounce the effects of caffeine. The purpose of this study was to evaluate the effects of menstrual phase and caffeine supplementation on physical and cognitive performances of women exercising in the heat. Six recreationally active female subjects (20.3 ± 1.6 yr, 1.67 ± 0.05 m, 69.3 ± 5.5 kg, 49.8 ± 3.3 ml·kg−1·min−1) concurrently taking monophasic OCS volunteered for this study. Each subject completed four trials: in the early follicular (EF, days 3–5) and midfollicuar (MF, days 19–21) phases of the menstrual cycle, after administration of either a placebo (P, corn starch) or caffeine (C, 5.5 mg/kg). Placebo and caffeine were administered in 355 mL “diet” cranberry drink (0 kcal), 1 hour prior to performing a self‐paced 5km time trial (TT) in the heat (29.6 ± 0.1°C, 55.8 ± 1.5 % relative humidity). Heart rate was recorded continuously and RPE was collected at 1‐km intervals. Oral temperature, Profile of Mood States (POMS) questionnaires and 2 tests of reaction and cognition (FitLight) were performed immediately prior to and following exercise. Time trial performance was improved in the EF‐C trial vs. EF‐P, ML‐C and ML‐P (1883 ± 203 vs. 1918 ± 224, 1898 ± 196, 1907 ± 205 seconds). Oral temperature tended to be elevated post‐TT in EF‐C vs. all other trials (37.4 vs. ~37.0 °C), while HR AUC tended to be decreased in the EF trials (5404 ± 167 vs. 5544 ± 181 beats, p = 0.09). The POMS Fatigue index was significantly higher post‐TT in the ML‐C trial (15.0 ± 1.9 vs 12.7 ± 0.4, 10.8 ± 1.1, ±11.2 ± 1.0). RPE and cognitive test responses were not different between trials. In heat stress, caffeine improves time trial performance in the EF phase despite an increased post‐exercise oral temperature. While heart rate response tended to be lower in the EF phase, no differences were observed in any other physical or cognitive performance measure between trials.

Support or Funding Information

Scotia Scholars Award, Nova Scotia Health Research Foundation

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Abrin, a Type II Ribosome Inactivating Protein: Differential Cytotoxicity and Development of the Vaccine Against its Lethality
Authors: Tiwari Vinita , Karande Anjali A
Published: June 2021

The plant toxin, Abrin, a type II ribosome inactivating protein, is extremely lethal, the human fatal dose being ~1 μg/kg body weight. Abrin has been classified as an agent for bioterrorism, which is of huge concern. On the other hand, the high toxic property of abrin has been employed in generating immunotoxins, where its toxin moiety is conjugated to cell surface marker specific antibodies for cell targeted killing.

Different cell types exhibit variable levels of sensitivity to abrin toxicity. To gain insights into this, two cell lines requiring strikingly different IC50 of abrin for inactivating ribosomes were studied. In KB cells, the abrin A chain was found to be sequestered from the cytoplasm into the nucleus by a protein called Brain acid soluble protein (BASP‐1), enabling the cells to resist abrin‐mediated inhibition of protein synthesis. In Ovcar‐3 cells that express negligible amounts of BASP‐1, the A chain remains in the cytosol to exert its N‐glycosidase activity, therefore succumb to low concentrations of abrin. In contrast, when the apoptosis inducing activity of abrin was examined, both the cells showed comparable apoptotic population. Employing conjugates of the wild type and active site mutant ABA with the ricin B chain it was found that abrin‐induced apoptosis was dependent on inhibition of protein synthesis leading to ER‐stress in Ovcar‐3 cells, but not in KB cells. Direct DNA damage caused by the abrin A chain sequestered in the nucleus might be contributing to the apoptosis in KB cells.

Towards establishing vaccines to counteract abrin‐induced lethality, we designed a recombinant chimeric protein of Abrin A chain and Abrus precatorius agglutinin A chain on the basis of epitope specificity. Abrin part of the chimera contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Importantly, the chimera harboured no enzymatic activity and was found to protect 100 % mice from abrin challenge upto 45 X LD50 dose. Thus the chimera appears to be potential vaccine against abrin induced lethality.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Compensatory regulation of Extracellular Pyrophosphate Metabolism in Vascular Smooth Muscle Cells during Early Calcification
Authors: Bellosta Ricardo Villa
Published: June 2021

Hydroxyapatitedeposition on the medial layer of the aortic walls is the hallmark of vascularcalcification and the most common complication in aging individuals andin patients with diabetes and those undergoing hemodialysis. Hyperphosphatemiais the main risk factor for vascular calcification and extracellularpyrophosphate (ePPi) is a potent physicochemical inhibitor of hydroxyapatitecrystal formation. Most ePPi is degraded to inorganic phosphate (Pi) by tissue non‐specific alkaline phosphatate (TNAP) in the aortic wall. Moreover, ePPiis generated enzymatically by hydrolysis of extracellular ATP by the enzyme ectonucleotidepyrophosphatase/phosphodiesterase 1 (eNPP1). Extracellular ATP is alsohydrolyzed by the ectonucleoside triphosphate diphosphohydrolase 1 (eNPTD1),releasing Pi. This study analyzed changes in extracellularpyrophosphate metabolism during the calcification process.

Pi‐induced calcification of ex vivo‐culturedaortic rings resulted in calcium accumulation after 7 days. This accumulation was enhanced when aortic walls were devitalized (118.9 μmolCa2+/gaorta vs. 433 μmolCa2+/g aorta, respectively). Bone morphogenic protein 2 (BMP2)expression was associated with calcium accumulation in Pi‐induced calcificationin cultured aortic rings, as well as in cultured vascular smooth muscle cells (VSMCs);and in calcitriol‐induced calcification in rats. Hydroxyapatite dose‐dependently induced BMP2 overexpression in VSMCs. TNAP mRNA levels and activity were found to be downregulated in early phases and upregulated in later phases of calcification in all three models studied. eNPP1 increased from early to later phases of calcification, whereas eNTPD1 was downregulated during later phases. Synthesis of pyrophosphate in VSMCs increased significantly over time, in all three models studied. Because the rate of pyrophosphate hydrolysis was100 times slower than the rate of ATP hydrolysis (Vmax values of 56.7 and 5016 pmol*mg−1*min−1,respectively, and Km values of 215 μmol/L pyrophosphate and 512 μmol/L ATP, respectively), pyrophosphate synthesis is determined mainly by the ratio ofeNPP1 to eNTPD1 activity. Hydroxyapatite also induces increments both in TNAP and eNPP1/eNTPD1 ratio in VSMCs.

These findings indicate that pyrophosphate synthesis increases in VSMCs during early calcification. Moreover, BMP2 may be a good marker of calcification, especially during early phases. By contrast, TNAP expression is not a good marker of calcification due to its regulation by various stimuli.

Support or Funding Information

This study was supported by grant SAF‐2014‐60699‐JIN from the Spanish Mini sterio deEconomía y Competitividad (MINECO).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Characterizing the Interactions between Intrinsically Disordered Transactivation Domains and the KIX Domain
Authors: Xiong Junwen , Huang Yongqi
Published: June 2021

Intrinsically disordered proteins (IDPs) are widely involved in cellular processes related to signal transduction and molecular recognition. Many IDPs interact with their biological targets via short recognition segments and different IDPs or different segments of an IDP are able to interact with a common target. The kinase‐inducible domain interacting (KIX) domain of the transcriptional coactivator CBP protein contains two distinct binding sites and is able to bind to numerous disordered transactivation domains (TAD) carrying the “ΦXXΦΦ” motif, where “Φ” is a hydrophobic residue, and “X” is an arbitrary residue. In this study we investigated the binding kinetics of various disordered TADs to the KIX domain via computer simulation and stopped‐flow technique. We found that the binding rates were heavily affected by salt concentration, indicating the involvement of long‐range electrostatic interactions during association. The basal rate constants derived from experiments under high salt conditions were similar for different KIX binding peptides. However, both experimental determined and theoretical predicted values indicated that the binding rates for peptides with the MLL site were greater than those for peptides with the c‐Myb site under low salt conditions. Electrostatic potential analysis showed that the MLL site was more positively charged than the c‐Myb site. Therefore, favorable electrostatic interactions between the MLL site and the negatively charged residues within the KIX binding peptides may steer the conformational search process and enhance the association. Site‐directed mutagenesis removing the positively charged residues on KIX domain significantly reduced the association rate constant with minor effect on the dissociation rate constant. Our results suggest that electrostatic interactions may be widely involved in interactions between disordered TAD and the KIX domain to achieve rapid signaling.

Support or Funding Information

This work was supported by National Natural Science Foundation of China (Grant number: 21603121) and Hubei University of Technology.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypertension alters Gut Microbial Metabolites
Authors: Cheema M. Umar , Pluznick Jennifer
Published: June 2021

Hypertension is a global public health challenge. Although multiple host signaling pathways have been discovered to play a role in hypertension, recent studies have revealed an important role of the commensal gut microbiota in contributing to blood pressure regulation. The gut microbiota can affect the host through the production of metabolites which activate signaling pathways in the host; these metabolites include those thought to largely promote host health, such as short chain fatty acids, as well as metabolites which are known to be uremic toxins (p‐cresol sulphate, indoxyl sulphate). In this study, we hypothesized that hypertension would alter gut microbial metabolite production. Furthermore, we hypothesized that an unbiased screen for changes in gut microbial metabolites would allow us to identify novel microbial metabolites. To pursue these hypotheses, six week old C57BL/6 conventional (conv, n=6) and germ‐free (GF, n=6) mice were infused with angiotensin‐II (AngII) for 4 weeks (400ng.kg−1.min−1; Alzet 1004); in parallel control groups, conv (n=6) and GF (n=6) mice received saline via minipumps. The inclusion of the GF group allows us to distinguish changes in host metabolites from changes in microbial metabolites. Following minipump implantation, animals were housed singly to prevent cross‐contamination of microbiota. At the end of fourth week, feces and blood was collected from mice. Both plasma and feces samples were processed and analyzed by using Liquid Chromatography‐Tandem Mass Spectroscopy (LC‐MS/MS) for metabolite detection (Metabalon). In feces, 33 of the top 35 metabolites which were significantly upregulated after angiotensin‐II treatment in conventional mice (saline‐conv vs. AngII‐conv) either were not detected or did not change in germ‐free mice (saline‐GF vs. AngII‐GF), indicating that they are of microbial origin. The most significant among them are choline phosphate (phospholipid metabolite, p ≤0.0029), taurohyodeoxycholic acid (bile acid metabolite, p ≤0.0203), taurolithocholate (bile acid metabolite, p ≤0.0093), and taurodeoxy cholate (bile acid metabolite, p ≤0.0166). In plasma, there were 11 metabolites which were significantly upregulated in AngII‐conv vs. saline‐conv; none of these 11 metabolites were upregulated by AngII in GF mice (saline‐GF vs. AngII‐GF). These metabolites include 4‐ethylphenylsulphate (benzoate metabolism, p ≤0.0001), p‐cresol sulfate (benzoate metabolism, known uremic toxin, p ≤0.0026), p‐cresol glucuronide (Tyrosine metabolism, p ≤0.0001), and taurodeoxycholate (Bile acid metabolite, p ≤0.0273). In summary, these data indicate that the great majority of metabolites which are upregulated in hypertension are gut microbial in origin, further strengthening the argument that the gut microbiome plays an important role in influencing host physiology in hypertension.

Support or Funding Information

American Heart Association (AHA)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mitochondrial‐targeted H2S Donor (AP39) Ameliorates Doxorubicin‐Induced Cardiomyopathy
Authors: Veeranki Sudhakar
Published: June 2021

Although doxorubicin cardiomyopathy is a lethal disease, currently there are no effective treatments available. Doxorubicin is a potent inducer of mitochondrial reactive oxygen species (ROS), thus leading to mitochondrial damage and dysfunction. Hydrogen sulfide, a gaseous signaling molecule, is actively produced in mitochondria and impacts its function especially during stress states. Here, we tested if mitochondrial‐targeted H2S donors can ameliorate the myocardial mitochondrial dysfunction induced by the oncological drug. We used three‐months‐old C57 mice (n=8) to induce doxorubicin cardiomyopathy and treated them with different doses of AP39 compound (an H2S donor). We have characterized the histological, gravimetric and molecular changes after the treatments in the myocardium. The results suggested that the mitochondrial‐targeted H2S donor has the potential for ameliorating myocardial mitochondrial dysfunction and doxorubicin cardiomyopathy.

Support or Funding Information

American Heart Association‐17SDG33670578 to Dr. Veeranki and HL074185.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Influence of Beta‐1 Adrenergic Receptor Genotype on Cardiovascular Response to Exercise in Healthy Subjects
Authors: Kelley Eli F , Snyder Eric M , Johnson Bruce D
Published: June 2021

Background

: Research suggests the beta‐1 adrenergic receptor (ADRB1) has been shown to play a functional role in cardiomyocyte function and accounts for up to 80% of the cardiac tissue adrenergic receptors with ADRB1 stimulation increasing cardiac rate, contractility, and work. Multiple polymorphisms of the ADRB1 have been identified such as the Gly49 polymorphism that includes at least one glycine (Gly) for serine (Ser) at amino acid 49 resulting in either homozygous for Gly (Gly49Gly) or heterozygous for Gly (Gly49Ser) polymorphisms. The Gly49 polymorphism has been shown to have decreased receptor density, decreased cAMP accumulation, and a dampening influence on the cardiostimulant effect during norepinephrine infusion. Heart failure patients with this polymorphism (Gly49) have also been shown to have improved cardiac function and decreased mortality risk, but if there is an effect in healthy subjects is less clear. This suggests the Gly49 polymorphism may have cardioprotective effects similar to that of a beta‐blocker.

Purpose

The purpose of this study was to determine the effects of the Gly/Ser polymorphism at position 49 of the ADRB1on the cardiovascular response to exercise in healthy subjects.

Methods

We performed genotyping of the ADRB1 (amino acid 49) and high‐intensity, steady‐state exercise on 71 healthy subjects (Ser49Ser = 52, Gly49Ser = 19).

Results

There were no differences between genotype groups in age, height, weight, BMI, or watts achieved (age = 28.9 ± 5.6yrs., 30.6 ± 6.4yrs., height = 173.6 ± 9.9cm, 174 ± 7.5cm, weight = 74.4 ± 13.3kg, 71.9 ± 13.5kg, BMI = 24.6 ± 3.5, 23.6 ± 3.3, and watts = 223.8 ± 76.8, 205 ± 49.4, for Ser49Ser and Gly49Ser respectively). Additionally, there were no differences for genotype groups for cardiac output (CO), systolic blood pressure (BPsys), or diastolic blood pressure (BPdias) at rest, peak exercise, or in change from rest to peak exercise. The genotype groups differed significantly in heart rate (HRmax) at peak exercise and cardiac index at rest (CI) (HRmax = 184.2 ± 9.5bpm, 190.7 ± 10.6bpm, CI = 0.063 ± 0.014, 0.071 ± 0.013, for Ser49Ser and Gly49Ser respectively). There was a trend towards significance (p = 0.058) for the change in stroke volume from rest to peak exercise (ΔSV) (0.016 ± 0.018L, 0.0076 ± 0.012L, for Ser49Ser and Gly49Ser respectively).

Conclusion

: These data suggest genetic variations of the ADRB1 may influence cardiovascular responses to exercise in healthy subjects.

Support or Funding Information

NIH grants: HL108962‐06

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hookah Smoking Causes an Acute Adverse Effect on Arterial Stiffness and Wave Reflections in Young Adults
Authors: Rezk‐Hanna Mary , Doering Lynn , Robbins Wendie , Sarna Linda , Elashoff Robert M , Victor Ronald G
Published: June 2021

Hookah (waterpipe) smoking is a centuries‐old, revived yet understudied epidemic of tobacco use. Despite being heavily advertised and glamorized in the media as a healthier alternative to cigarettes, the toxicology of hookah smoke suggest otherwise. Cigarette smoking unequivocally causes an acute increase in arterial stiffness, but whether hookah does the same is unknown. In 48 young healthy habitual hookah but not cigarette smokers, we measured heart rate, peripheral and central blood pressure, carotid‐femoral pulse wave velocity (measure of arterial stiffness), aortic augmentation index (measure of wave reflection), plasma nicotine, and exhaled carbon monoxide (CO) before and after 30 minutes of ad lib hookah smoking. Hookah smoking increased heart rate by +16 ± 1 beats/min and mean brachial arterial pressure by +6 ± 1 mmHg (both p < 0.05, mean ± SE). Most importantly, it increased carotid‐femoral pulse wave velocity and aortic augmentation index by +0.66 ± 0.09 m/s−1and +8.76 ± 3.99%, respectively (p <0.05, mean ± SE), denoting increased acute arterial stiffness. These vascular effects were accompanied by increases in plasma nicotine concentration (+5.8 ± 1.2 ng/ml, p<0.05) and expired CO (+25.44 ± 1.68 ppm, p< 0.05). All these parameters were unchanged during time‐control studies (n=14). Thus, in contrast to effective media marketing of hookah as a safer alternative to cigarettes, the present study shows for the first time that in young adult hookah smokers, a single hookah smoking session causes an acute increase in arterial stiffness of comparable magnitude to what has been previously reported for cigarettes. Further research is warranted to determine whether habitual hookah smoking accelerates the age‐dependent development of hypertension and its cardiovascular complications.

Support or Funding Information

This study was funded by the Tobacco‐Related Disease Research Program to Dr. Mary Rezk‐ Hanna (#23DT‐0102) and Dr. Ronald Victor (#22XT‐0017).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regional and sex differences in cerebral vasomotor reactivity to carbon dioxide
Authors: LIU JIE , Falvo Michael J. , Brewer Kelly , Favre Michelle E. , Serrador Jorge M.
Published: June 2021

Studies on cerebral vasomotor reactivity (CVMR) to carbon dioxide (CO2) are often limited to middle cerebral artery (MCA), and rarely include anterior cerebral artery (ACA) and/or vertebral artery (VA); In addition, comparison of reactivity across vessels in the same individuals is rarely performed; Moreover, sex difference in CVMR has also not been carefully investigated. Therefore, it remains unknown whether there are differences in CVMR across arterial territories and/or between females and males. Twenty‐five young healthy subjects (15 females; age: 19–37 yrs, 27±5 yrs) were enrolled. The cerebral blood flow velocities (CBFVs) at the MCA, ACA and VA were simultaneously and continuously recorded with transcranial Doppler during 3‐min resting ventilation, 2‐min inspiration of 8% CO2, 21% O2, balance nitrogen, and 2‐min mild hyperventilation, in the sitting position. The CVMR of each artery is expressed as the percent change in its CBFV per mmHg change in end‐tidal CO2, as quantified by the slope of this relationship. The results are presented as Mean±SD. The experimental protocol resulted in a variation of end‐tidal CO2 from 31.8±4.7 to 46.6±5.5 (baseline, 40.4±3.5) mmHg, with a slight variation of mean blood pressure from 92±13 to 99±13 (baseline, 94±12) mmHg. The repeated‐measures ANOVA for multiple comparisons with Bonferroni correction indicated that the CVMR slope was significantly lower in the VA (1.85±0.61 %/mmHg) than in the MCA (2.30±1.04, P = 0.023) or ACA (2.33±0.92, P = 0.004). Females generally showed steeper CVMR slope than males (2.43±0.91 vs. 1.77±0.31, P = 0.019, for the 3‐artery averaged value), with no interaction found between sex and arterial territory factors. Based on these results, the CVMR appears lower in the posterior (vertebrobasilar) circulation than in the anterior circulation. Consistent with previous data we also found females had higher CVMR values in all arteries than males. The observed regional and sex CVMR differences should play an important role when assessing the cerebral blood flow response to other physiological situations (e.g. dynamic exercise; orthostatic, hypoxia, heat or cold stress), and might explain some neurological symptoms relevant to the posterior circulation ischemia and/or sex differences, which merits further investigation. Future studies are planned to examine the pressure‐ and/or flow‐induced concurrent diameter changes of the insonated artery, when using CBFV rather than volumetric cerebral blood flow to assess the CVMR.

Support or Funding Information

Supported by the War Related Illness & Injury Study Center, Veterans Administration and NIH grant R21DC009900.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The effect of exercise on purinergic receptor‐mediated cerebrovascular dysfunction in Alzheimer's disease
Authors: Hong Junyoung , Lee Jonghae , Eriksen Jason , Park Yoonjung
Published: June 2021

Introduction

Cerebrovascular dysfunction is a critical initial step of Alzheimer's disease (AD). Adenosine triphosphate (ATP) regulates cerebral blood flow through purinergic receptors. The aim of this study is to investigate the protective effect of exercise training on ATP‐induced purinergic receptor‐mediated cerebrovascular dysfunction in the AD and its underlying mechanisms.

Methods

We used the control mice (CON; C57BL/6), CON with exercise training (CON‐EX), AD mice (AD; APP/PS1) and AD with EX (AD‐EX). At 7 to 9 months of age, CON‐EX and AD‐EX mice underwent 10–12 weeks of aerobic exercise training, which consisted of 1 hour of treadmill running at 15m/min at a 5% grade. To test the purinergic receptor‐dependent vasoreactivity, a posterior cerebral artery (PCA) was isolated and ATP (2‐MeS‐ATP, 1 nmol/L to 10 μmol/L)‐induced dose‐dependent vascular dilation/constriction response was determined at 10–12 months of age. Western blotting was utilized to analyze the expression of P2Y2 receptors (P2Y2R), total eNOS (t‐eNOS) and phosphorylated eNOS (p‐eNOS) in the brain.

Results

ATP induced vasodilation of PCA in CON and CON+EX mice, but it induced vasoconstriction in AD mice. Notably, exercise training reverses ATP‐induced vasoconstriction in the AD to vasodilation (AD+EX) comparable to CON mice. Western blotting data demonstrated that P2Y2R and p‐eNOS expression were significantly diminished in AD mice compared to CON mice, but they were elevated in AD‐EX mice brain. There was no significant difference in t‐eNOS expression among mice groups.

Conclusion

Our findings suggest that ATP‐induced purinergic receptor‐dependent cerebrovascular function is impaired in the AD. However, exercise training reverses ATP‐induced purinergic receptor‐dependent vasoconstriction to vasodilation mainly through the alteration of P2Y2R and p‐eNOS expression in the AD‐EX.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Understanding Heart Rate and Blood Pressure in Older Adults During Ongoing Single‐Task and Dual‐Task Balance Testing Protocols
Authors: Dickens Cameron , Bigelow Kimberly E. , Crecelius Anne R.
Published: June 2021

Vestibular function is known to decline as a function of aging in adults, leading to a risk for falls in otherwise healthy people. General cardiovascular function also declines with age, and can increase the risk of cardiac events. Increasingly, progressively challenging tasks are being incorporated into balance testing, some of which might increase cardiovascular stress and yet there is little research to characterize the systemic cardiovascular responses to various balance protocols in aging humans. Therefore, the purpose of this project was to understand changes in heart rate and blood pressure during ongoing balance testing protocols in aging populations. Ten subjects ages 18 to 40 and nine subjects ages 65 and above completed balance testing including under two conditions: a progressive challenge single task (removal of visual and kinesthetic cues); and a dual task (mental arithmetic and balancing a ball on a tray). Blood pressure (via arm cuff) and heart rate (via ECG) were obtained prior to and during the task and balance was assessed via posturography (force plate). As anticipated, older individuals had impaired balance, evidenced by increased sway and greater changes in center of pressure. While both age groups saw minimal changes in cardiovascular variables during the single‐task protocols, the older group experienced augmented changes from control conditions during certain dual‐task protocols compared to their younger counterparts. The older age group exhibited greater changes in systolic pressure (13 ± 3 mmHg vs. 6 ± 3 mmHg), mean arterial pressure (7 ± 2 mmHg vs. 6 ± 2 mmHg), and heart rate (3 ± 1 bpm vs. 0 ± 2 bpm) during the physical dual‐task condition (holding a tray). Overall, the young and old age groups experienced similar cardiovascular effects during ongoing balance testing, except during the physical dual‐task challenge, where the younger subjects experienced much more mild effects than the older subjects.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Preeclampsia induces the acquired salt‐sensitivity characteristics via increased vasopressin secretion in the postpartum stage
Authors: Shinohara Keisuke , Matsuura Taku , Hirooka Yoshitaka , Tsutsui Hiroyuki
Published: June 2021

Background

Women with a history of preeclampsia exhibit increased salt‐sensitivity in the postpartum stage, which might account for their increased risk of future cardiovascular disease. However, it is unclear whether the increased salt‐sensitivity is a cause or effect of preeclampsia. Various factors, such as kidney injury and renin‐angiotensin system, are associated with salt‐sensitive hypertension. Vasopressin may also play a role in the pathogenesis of both preeclampsia and salt‐sensitive hypertension.

Purpose

The aim of the present study was to investigate whether the onset of preeclampsia in subjects with originally normal salt‐sensitivity induces increased salt‐sensitivity in the postpartum stage, and to elucidate the possible mechanisms.

Methods and Results

We used the reduced uterine perfusion pressure (RUPP) rat model, which is widely used as an acquired model of preeclampsia. Pregnant Sprague‐Dawley rats at day 14 of gestation were divided into two groups: RUPP‐operated (n=7) and sham‐operated (SHAM) controls (n=8). At 3 weeks postpartum, a high‐salt diet was initiated for 1 week. The high‐salt diet‐induced changes in mean arterial pressure (MAP) and the sodium sensitive index (SSI=ΔMAP/Δurine sodium) were significantly greater in the RUPP group than in the SHAM group (ΔMAP: 19.8±2.7 vs. 9.3±1.7 mmHg, SSI: 801±140 vs. 421±95.3 mmHg/mmol, both p<0.05). Creatinine clearance was not significantly different between groups, and histological studies revealed that both groups had normal kidney structures. Plasma renin activity and plasma aldosterone levels did not differ between groups. Levels of plasma copeptin, a substitute for plasma vasopressin, were significantly increased in the RUPP group compared with the SHAM group (150±20.3 vs. 98±18.6 pg/ml, p<0.05). Double immunofluorescence staining also revealed that expression of c‐Fos, a marker of neural activity, in vasopressin‐producing neurons was significantly increased in the hypothalamic paraventricular nucleus in the RUPP group compared with the SHAM group (% of c‐Fos positive neurons in vasopressin neurons: 45.8±7.1% vs. 23.1±2.0%, p<0.05). Gavage administration of the dual V1a/V2 vasopressin receptor antagonist conivaptan (1.0 mg/kg/day) while on the high‐salt diet attenuated the increase in MAP and decreased SSI in the RUPP rats (ΔMAP: 9.5±2.1 mmHg, SSI: 437±76.9 mmHg/mmol, n=4), but not in the SHAM rats (ΔMAP: 14.5±2.8 mmHg, SSI: 574±106 mmHg/mmol, n=5).

Conclusion

Preeclampsia caused salt‐sensitivity of blood pressure in the postpartum stage, probably due to increased vasopressin secretion.

Support or Funding Information

Kanae Foundation for the Promotion of Medical Science

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
An Atherogenic Diet Exacerbates Vascular Injury in an Experimental Model of Systemic lupus Erythematosus
Authors: Coleman Taylor , McClung Daniel , Ryan Michael J , Taylor Erin B
Published: June 2021

Patients with systemic autoimmune diseases such as systemic lupus erythematosus (SLE) have an increased risk of developing premature atherosclerotic cardiovascular disease (CVD), which is a major contributor to morbidity and mortality in this patient population. Specifically, patients with SLE have evidence of vascular disease including endothelial dysfunction, arterial stiffness, and coronary perfusion abnormalities, all of which predispose them to the development of atherosclerotic lesions. Our laboratory has shown that an established female mouse model of SLE (NZBWF1) develops impaired endothelial dependent relaxation compared to age matched healthy controls (female NZW mice). In the present study, we hypothesized that SLE mice fed an atherogenic diet will have accelerated vascular injury indicative of premature atherosclerotic disease. In order to test this hypothesis, female control (NZW, n=20) and SLE (NZBWF1, n=20) mice were fed normal chow or a high fat diet supplemented with 0.5% cholate (HFD+cholate) for 14 weeks. Body weight and body composition were monitored by Echo MRI biweekly over the course of the study. At the conclusion of the study both carotid arteries and aortas were isolated from control and SLE mice. Carotid rings were suspended in organ chamber baths where endothelium‐dependent and endothelium‐independent relaxation were the concentration responses (10−8 to10−4 M) to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in vessels pre‐contracted with the thromboxane mimetic U46619 (0.4 μg/mL). HFD+cholate did not alter maximal ACh (10−4 M) mediated relaxation (70.1±3.4% vs. 75.2±2.1% p=0.33) in control mice. However, SLE mice fed HFD+cholate had an impaired relaxation response to ACh (10−4 M) as compared to SLE mice fed normal chow (65.6±2.3% vs. 43.6±7.2%, p=0.02). SNP‐mediated relaxation was not different between the mice fed different diets in either control or SLE animals, indicating that the impaired ACh response in SLE mice is endothelial dependent. In order to examine the impact of HFD+cholate on atherosclerotic lesion formation, isolated aortas were subjected to en face staining using Sudan IV. Preliminary data suggest that control mice fed HFD+cholate did not develop atherosclerotic plaques, but SLE fed HFD+cholate showed evidence of plaques in the aortic arch. Taken together, these data suggest that the immune system dysfunction present in SLE may accelerate the progression of diet‐induced atherosclerosis.

Support or Funding Information

E.B.T. was supported by an individual NIH National Research Service Award (F32HL137393). This work was supported by Veteran's Administration Merit award (BX002604‐01A2) to M.J.R. and NIH NHLBI awards PO1HL051971, P20GM104357 to UMMC‐Department of Physiology and Biophysics.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.