bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF RADIATION ON CUTANEOUS MICROVASCULAR FUNCTION IN THE INTACT HUMAN CIRCULATION
Authors: Banister Heather R , Parr Shannon K , Turpin Vanessa‐Rose G , Ade Carl J 
Published: June 2021

Radiation is a commonly used treatment for various types of cancer, however it is often associated with an increased risk of cardiovascular disease (CVD). Previous animal studies have shown a significant decreased relaxation in irradiated arteries in response to Acetylcholine. However, there is a paucity of knowledge on the effects of radiation within the intact human circulation. Given that changes vascular function occurs early in the progression of numerous cardiovascular and metabolic diseases characterization of the microvascular responses to radiation treatment is critical. Therefore, the primary was to determine the effects of cancer treatment radiation on cutaneous microvascular reactivity in breast cancer patients.METHODSThe present study utilized a longitudinal study design in breast cancer patients receiving radiation therapy. Cutaneous microvascular reactivity to Acetylcholine (ACh) was evaluated following radiation exposure in breast cancer patients at the site of radiation treatment and at a control non‐irradiated site. Briefly, red blood cell flux was measured as an index of cutaneous blood flow via laser Doppler flowmetry with ACh mediated vasodilation determined by iontophoresis drug delivery. Data are expressed as cutaneous vascular conductance.RESULTSTo date, 4 patients have completed the study (planned enrollment of 15 patients). Cutaneous vascular conductance to ACh was significantly attenuated following a total cumulative dose of 1950 ± 719 cGy. Similarly, the total ACh response was decreased in the radiated tissue. The forth coming patients will provide additional insight into the effects of radiation exposure on microvascular reactivity. Furthermore, we will be able to provide insight into the role coexisting risk factors of metabolic syndrome and preexisting atherosclerosis on radiation‐induced vascular dysfunction.CONCLUSIONThis study demonstrates that low doses of radiation for cancer treatment attenuate cutaneous microvascular function, which may have long‐term implications for cardiovascular health in these patients.Support or Funding InformationN/AThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Post‐Exercise Oxygen Uptake and Muscle Oxygenation in Pediatric Heart Transplant Recipients
Authors: Kosokowsky Kylee , Boyes Natasha G , Lahti Dana S , Blushke Corey R , Marciniuk Darcy , Butcher Scotty J , Erlandson Marta C , Wright Kristi D , Pockett Charissa , Tomczak Corey R 
Published: June 2021

Pediatric heart transplant recipients (HTR) have reduced exercise tolerance and peak oxygen uptake (VO2) values are 57–73% of age‐predicted norms. Slow post‐exercise VO2 and muscle oxygenation recovery are related to exercise intolerance. However, despite clear exercise tolerance limitations and post‐exercise fatigue, VO2 and muscle oxygenation during recovery responses are unknown in this population.PurposeWe tested the hypothesis that both post‐exercise VO2 recovery and muscle oxygenation recovery would be slower after peak exercise in pediatric HTR compared to controls.MethodsFive pediatric HTR (mean ± SD age = 10.6 ± 3.0 years) and six healthy controls (age = 11.7 ± 2.7 years) performed cycle ergometry to peak exercise followed by 5 minutes of 20‐W cycle recovery. Pulmonary VO2 and muscle oxygenation (vastus lateralis tissue oxygenation index, TOI using near infrared spectroscopy) were sampled continuously during exercise and recovery. Data were linearly interpolated to 1‐s intervals, and both VO2 and TOI data were averaged into 5‐s and 10‐s time bins, respectively. VO2 recovery data were mono‐exponentially curve‐fitted to yield a recovery time constant (tau). TOI recovery was normalized from 0% (end exercise) to 100% (5 min post‐exercise) and data analyzed at set time points to characterize TOI time course changes (0s, 15s, 30s, 60s, 90s, 120s, 180S, 240s, and 300s). Statistical analyses included independent t‐tests for VO2 data and a between‐within (2 × 9, group × time) factorial ANOVA for TOI time course changes. Significance was accepted at p< 0.05.ResultsRecovery VO2 tau was significantly slower in pediatric HTR compared to healthy controls (68 ± 17 vs. 47 ± 12 s, respectively; p=0.044). There was a significant group × time interaction for TOI recovery (p=0.003) where TOI in HTR was significantly lower compared to controls at 15s (8 ± 8 vs. 46 ± 19%; p=0.003), 30s (22 ± 13 vs. 91 ± 31%; p=0.001), and 60s (47 ± 23 vs. 117 ± 36%; p=0.005). TOI was not statistically different between groups by 90s onwards (all p>0.05).ConclusionsPost‐exercise VO2 and TOI recovery are prolonged in pediatric HTR compared to healthy controls. These findings suggest that non‐cardiac factors may contribute to the excessive recovery time following peak exercise in pediatric HTR.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Is Arterial Stiffness Increased in Pediatric Heart Transplant Recipients?
Authors: Singh Shreya , Blushke Corey R , Boyes Natasha G , Lahti Dana S , Kosokowsky Kylee , Marciniuk Darcy , Butcher Scotty , Erlandson Marta C , Wright Kristi D , Pharis Scott , Pockett Charissa , Tomczak Corey R 
Published: June 2021

Adult heart transplant recipients (HTR) have increased arterial stiffness, despite resolution of the underlying pre‐transplant diagnosis. The impaired vascular function may also contribute to the reported impaired exercise tolerance in these patients. Patient age and the duration and sequela of the pre‐transplant cardiovascular disorder significantly contribute to the increased arterial stiffness observed in adult HTR, while the direct role of immunosuppressive therapies is less understood. We tested the hypothesis that despite young age, pediatric HTR will display increased arterial stiffness owing to their significant pre‐transplant cardiovascular disease and post‐transplant physical inactivity. We also tested the hypothesis that arterial stiffness would be related to exercise tolerance (peak oxygen uptake, VO2).METHODSSix pediatric HTR (3 females and 3 males; 10 ± 3 years) and 12 age‐ and sex‐matched healthy controls (6 females and 6 males; 10 ± 2 years) were studied. Carotid‐radial pulse‐wave velocity by ECG‐gated sequential applanation tonometry was used to determine arterial stiffness. HTR subjects also completed a peak VO2 test by cycle ergometry. Data were analyzed through an independent samples t‐test with significance differences being accepted at P < 0.05.RESULTSPulse wave velocity was not different between HTR (8.50 ± 1.93 m/s) and the healthy controls (8.55 ± 1.52 m/s, P = 0.951). In addition, pulse wave velocity was not related to peak VO2 in HTR (r = −.529, P = 0.140).CONCLUSIONUnlike in adult HTR, pediatric HTR have normal arterial stiffness compared to healthy‐matched controls, and arterial stiffness was not related to peak VO2 in this pediatric population. These findings suggest that the pre‐transplant diagnosis sequela do not unfavorably alter arterial stiffness in young pediatric HTR and that reduced peak VO2 in pediatric HTR is not related to arterial stiffness.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Retrograde and Oscillatory Shear Remain Stable Across the Menstrual Cycle but Increase in Postmenopausal Women
Authors: Somani Yasina B , Kim Danielle Jin‐Kwang , Barrett Megan A , Ogot Akinyi , De Souza Mary Jane , Proctor David N 
Published: June 2021

Patterns of conduit artery shear are an important determinant of vascular function and increases to retrograde and oscillatory shear are associated with endothelial dysfunction, a key antecedent to atherosclerosis and cardiovascular disease. The adoption of this pro‐atherogenic profile described in humans is linked to chronological aging, and more recently, reproductive aging in women. To assess the potential influence of acute and chronic estrogen deficiency on arterial shear patterns, we studied premenopausal women (n=8, 22 ± 2 years) during the early follicular (Estradiol: 27.7± 9.2 pg/mL) and late follicular phase (Estradiol: 173.7 ± 144.3 pg/mL) of the menstrual cycle, and postmenopausal women (n=14, 60 ± 2 years, Estradiol: 22.3 ± 5.9) who were not on hormone therapy. Resting measures of brachial artery blood velocity and diameter were collected with Doppler ultrasound to determine mean, antegrade, and retrograde shear rates. Oscillatory shear index (OSI) was determined as the ratio between retrograde and antegrade shear rate. In premenopausal women, retrograde shear (−8.1 ± 2.8 vs. −7.6 ± 2.7 s−1, p=0.67) and OSI (0.07 ± 0.02 vs. 0.06 ± 0.03 a.u., p=0.89) were similar between menstrual phases, however these measures during both phases were significantly lower than in postmenopausal women (−13.3 ± 5.1 s−1, 0.21 ± 0.12 a.u., both p<0.05). These findings suggest that patterns of brachial artery shear remain stable across the menstrual cycle, despite fluctuations in estradiol. However, with prolonged estrogen deficiency secondary to menopause, retrograde and oscillatory shear are increased in the brachial artery, which likely contribute to endothelial dysfunction in postmenopausal women.Support or Funding InformationPenn State Jaffe EndowementThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Smooth muscle‐selective ablation of A‐kinase anchoring protein 150 (AKAP150) mitigates diabetes‐induced cardiac dysfunction
Authors: Zhang Deqing , Brittian Kenneth R , Bhatnagar Aruni , Nystoriak Matthew A 
Published: June 2021

Inadequate blood flow to the myocardium due to microvascular dysfunction may play a role in the development and progression of diabetic cardiomyopathy, although contributing mechanisms are poorly understood. Hyperglycemia, a hallmark of diabetes mellitus, promotes enhanced arterial tone via altered excitation‐contraction and ‐transcription coupling that is dependent upon kinase/phosphatase targeting to the membrane of vascular smooth muscle by the A‐kinase anchoring protein AKAP150. In this study, we tested the hypothesis that AKAP150‐dependent signaling in smooth muscle contributes to cardiac dysfunction in an experimental model of diabetes. We generated smooth muscle selective AKAP150‐null animals by crossing AKAP5‐floxed mice (Akap150fl/fl) with knock‐in mice expressing Cre recombinase under the control of SM22α (smCre). Offspring (AKAP150fl/fl‐smCre) were viable and demonstrated genetic recombination and loss of AKAP150 protein in vascular smooth muscle (aortic smooth muscle, mesenteric arteries, coronary arteries), but not in heart or brain tissues. Male AKAPfl/fl and AKAPfl/fl‐smCre animals (8–12 weeks) were maintained on a high fat/high sucrose (HFHS) diet for 20 weeks. Body weight and blood glucose (fasting and non‐fasting) were significantly elevated in HFHS groups compared to control chow‐fed animals at time points after 8 weeks. At 20 weeks, echocardiography revealed that AKAP150fl/fl animals on HFHS diet had significantly greater end systolic volume, as well as reduced ejection fraction and fractional shortening when compared to AKAP150fl/fl mice maintained on control diet for the same period. However, no significant differences in cardiac function or chamber dimensions were observed between AKAP150fl/fl‐smCre animals on HFHS versus AKAP150fl/f‐smCre animals on control diet. Our results suggest that AKAP150‐mediated signaling in vascular smooth muscle may contribute to altered cardiac function in a HFHS model of diabetes.Support or Funding InformationThis work was supported in part by grants from the National Institutes of Health (GM103492, HL142710) and American Heart Association (16SDG27260070),This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of the LPC‐ATX‐LPA Axis in the Development of Endothelial Dysfunction
Authors: Janovicz Anna , Kerkovits Nora Melinda , Majer Aliz , Balogh Lili , Balogh Andrea , Tigyi Gabor Joseph , Benyo Zoltan , Ruisanchez Eva 
Published: June 2021

IntroductionLysophosphatidylcoline (LPC) is a bioactive lipid component of low‐density lipoprotein (LDL) that plays an important role in the development of atherosclerosis. Based on literature data, LPC causes endothelial dysfunction through decreasing NO bioavailability, however, the underlying mechanisms are not completely understood. LPC can be hydrolyzed into LPA by the cell secreted enzyme, autotaxin (ATX). Our aim was to investigate the role of the LPC‐ATX‐LPA axis in the development of endothelial dysfunction.MethodsMyographic measurements were performed on thoracic aorta segments isolated from male, adult C57/Bl6 mice. We examined the effect of 18:1 LPC (10 μM) on the NO‐dependent vasorelaxation after a 20 min incubation. The vessels were pre‐contracted with phenilephrine (PE), subsequently increasing concentrations of acetyl‐choline (ACh) were added to evoke vasorelaxation. Some of the vessels were pre‐treated with the ATX inhibitor BMP‐22 (10 μM) or the LPA1,3 antagonist Ki16425 (10 μM). FS‐3 substrate assay was used to measure ATX activity of the aortic tissue.ResultsLPC significantly attenuated ACh‐induced vasorelaxation without influencing the effect of the NO‐donor sodium nitroprusside. Interestingly, LPC‐induced suppression of the endothelium‐dependent vasorelaxation was more severe in the proximal, than the distal aorta that is more prone to develop atherosclerotic plaques. The ATX inhibitor BMP‐22 decreased the endothelial dysfunction and its protective effect was proved to be more pronounced in the proximal as compared to the distal segments. In addition, FS‐3 assay measurement for ATX activity showed higher activity in the proximal, than the distal part of the aorta. The LPA1,3 receptor inhibitor Ki16425 also reduced the effect of LPC in the proximal but not in the distal aorta.ConclusionsOur study shows that ATX and LPA are involved in LPC‐induced endothelial dysfunction. The results suggest that in this process LPA acts through LPA1 and / or LPA3 receptors. According to the literature the development of atherosclerosis is faster and more severe on the proximal segment of the thoracic aorta, therefore the LPC‐ATX‐LPA system is likely to contribute to the progression of the disease.Support or Funding InformationSupported by the Hungarian NRDIO (OTKA K‐112964, K‐125174 and NVKP_16‐1‐2016‐0042) as well as by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Molecular Biology thematic programme of the Semmelweis University and by the EFOP‐3.6.3‐VEKOP‐16‐2017‐00009 grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Microbiome Product Urolithin A Abolishes TGFβ‐Dependent Stimulation of PAI‐1 in Renal Epithelial Cells
Authors: Chappell Mark C , Pingue Georgia , Pirro Nancy , Tallant Ann , Gallagher Patricia 
Published: June 2021

Introduction and HypothesisEllagitannins are abundant in various foods including fruits, nuts and wines, as well as plant‐based supplements. Urolithin A is derived from ellagitannins metabolism by the microbiome, is absorbed by the gut epithelium and may significantly contribute to the biological actions of ellagic acid. Previous studies demonstrate renal protective effects of both ellagic acid and urolithin A; however, the cellular mechanisms that underlie the benefits of urolithin A are unclear. Activation of the renal TGFβ‐PAI‐1 pathway is a key cellular event that contributes to fibrosis, oxidative stress and progressive kidney injury. Therefore, the current study assessed the effects of urolithin A on TGFβ‐induced stimulation of PAI‐1 in renal proximal tubule (PT) cells. We hypothesized that urolithin A would present protective effects to attenuate PAI‐1 expression in PT cells and exhibit greater potency than the parent compound ellagic acid.ResultsWe initially determined an optimal dose of TGFβ (0.1 to 10 ng/ml) to stimulate PAI‐1 release in the NRK‐52e cell line. Cells were maintained in serum free conditions for 48 hours prior to TGFβ treatment. At a concentration of 5 ng/ml, TGFβ increased PAI‐1 approximately 5‐fold (480 ± 35%, n=4; p<0.01) above unstimulated or basal levels following a 24 hour exposure. As expected, pretreatment with the TGFβ receptor (TGFβR) kinase inhibitor SB431542 (1 uM) abolished the increase in PAI‐1. Moreover, the EGFR kinase inhibitor AG1478 (1 μM) completely abrogated the PAI‐1 release in response to TGFβ and confirms earlier reports that TGFβ stimulation of PAI‐1 reflects the complete dependence on activation of the EGFR. In contrast, the cSRC kinase inhibitor SU6056 failed to block PAI‐1 release suggesting that TGFβ stimulates the ligand‐dependent transactivation of EGFR rather than direct cSRC activation of the EGFR. Similar to TGR and EGFR inhibition, pretreatment of the cells with urolithin A (40 μM) abolished the increase in PAI‐1 to TGFβ (5 ± 4% of basal release, n=4). Dose response studies of urolithin A revealed an ED50 of 22 ± 3 μM (n=3) to inhibit PAI‐1. Ellagic acid also inhibited TGFβ stimulation of PAI‐1 release, but was less potent (ED50 >50 μM) than Urolithin A.ConclusionWe conclude that the protective effects of urolithin A may involve inhibition of the TGFβ‐EGFR‐PAI‐1 pathway in renal epithelial cells. Although the precise inhibitory mechanisms are presently unknown, urolithin A may potentially target either TGFβR‐ or EGFR‐dependent kinases to abrogate PAI‐1 expression.Support or Funding InformationAHA Transformative Grant 18TPA34170522; Anonymous Contribution 15‐01401This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulation of gut microbiota by cyanidin 3‐glucoside in a mouse model of fatty liver disease
Authors: Wu Shusong , Liu Jie , He Ziyu , Tan Jijun , Liu Ming , Hou De‐Xing , He Jianhua 
Published: June 2021

Recent studies suggested that the dysbiosis of gut microbiota might be a leading cause of nonalcoholic fatty liver disease (NAFLD), and our previous study revealed that Lonicera caerulea L. berry, which is rich in cyanidin 3‐glucoside (C3G), has protective effects against high fat diet (HFD)‐induced fatty liver disease. The present study aimed to investigate the regulatory effect of C3G on gut microbiota in a mouse NAFLD model. C57BL/6N mice (n=4 for each group) were fed a normal diet (Research Diets D12450B), HFD (Research Diets D12492) only, or HFD containing 0.4% of C3G for 3 months based on our pilot test, liver sections were stained by hematoxylin–eosin, serum lipids and transaminases were measured with the automatic biochemical analyzer, and cecal microbiota was characterized by high throughput sequencing of 16S rDNA amplicons. Dietary supplement of C3G decreased fat deposition and improved liver histology in mice. Biomedical analysis indicated that C3G significantly decreased the ratio of low density lipoprotein cholesterol (LDL‐c) to high density lipoprotein cholesterol (HDL‐c), the level of triacylglycerol, and levels of transaminases including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of HFD‐fed mice. The analysis of high throughput sequencing data revealed that the relative abundance of Firmicutes was increased by HFD, but decreased by supplementing C3G; in addition, C3G increased the relative abundance of Bacteroidetes at the phylum level. Most notable microorganisms at the genus level were Lactococcus, Romboutsia and Clostridium; in particular, HFD increased the relative abundance of Lactococcus and Romboutsia, but decreased Clostridium, on the contrary, C3G inhibited Lactococcus and Romboutsia, but promoted the growth of Clostridium. These data demonstrated that C3G potentially attenuated HFD‐induced fatty liver disease by modulating gut microbiota especially up‐regulating Clostridium and down‐regulating Lactococcus and Romboutsia.Support or Funding InformationThis work was partially supported by National Natural Science Foundation of China (No. 31741115) and Hundred Talents Program of Hunan Province.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of the Speed of Body Weight Loss on Body Composition Changes and Energy Density for Body Weight Loss in Exercised Rats
Authors: Kitaguchi Mizuki , Maeda Megumi , Okamura Koji 
Published: June 2021

We examined the effects of the speed of body weight (BW) loss on changes in the body composition and energy required for BW loss in exercised rats. Rats (average BW: 275 g), were divided into a rapid weight reduction group (Rapid, n = 5), which was fasted for 3 days, and a slow weight reduction group (Slow, n = 5), which had their food restricted for 17 days in order to achieve comparable BW loss to the Rapid group. The rats were placed individually into a metabolic chamber with a 1‐m ladder inside. The water bottle was set at the top of the chamber, forcing the rats to climb the ladder to drink. The BW loss was −42.7 g (standard deviation [SD] 4.2) in the Rapid group and −43.8 g (SD 4.9) in the Slow group. The total energy expenditure was 95.1 kcal (SD 10.7) in the Rapid group and 555.6 kcal (SD 69.3) in the Slow group. Since the metabolizable energy was 0 kcal in the Rapid group and 521.1 kcal (SD 44.9) in the Slow group, the energy deficit was −95.1 kcal (10.7) in the Rapid group and −34.5 kcal (72.7) in the Slow group. Therefore, the energy density for BW loss by 1 kg was not significantly different between the Rapid group (2246 kcal [SD 320.3]) and the Slow group (734.6 kcal [SD 1631.6]). The estimated changes in the lean tissue (LT) and adipose tissue (AT) based on the energy density of LT (1.25 kcal/g) and AT (7.6 kcal/g) and the energy deficit did not differ significantly between the groups (LT: −36.0 g [SD 5.4] and AT: −6.8 g [SD 1.9] in the Rapid group and LT: −47.1 g [SD 11.8] and AT: 3.3 g [SD 11.6] in the Slow group). Therefore, the speed of BW loss had no marked effect on the changes in the body composition and energy required for BW loss in exercised rats. However, the increase in the AT observed in the Slow group is theoretically unlikely, suggesting the overestimation of energy intake (metabolizable energy) due to a decrease in the absorption rate or an increase in the energy density in the AT in this group.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
RhoA and MAPK Pathway in Toxin‐induced Production of TNF‐α during Clostridium difficile Infection
Authors: Sun Xingmin , Wang Shaohui , Feng Hanping 
Published: June 2021

Release of proinflammatory cytokines or other mediators from immune cells or intestinal epithelial cells is a critical activation event in C. difficile toxin‐mediated intestinal inflammation. In this study we investigated the role of TNF‐α in the pathogenesis of CDI using mouse model of toxin exposure or CDI, and dissected the roles of RhoGTPase and MAPK in TcdA‐induced production of TNF‐α by macrophages. We showed that inactivation of RhoA by TcdA activates p38 and ERK, which controls of TNF‐α production by macrophage Raw264.7 cells. We also demonstrated that calcium signaling regulates TcdA‐induced TNF‐α in macrophage cell line. Based on these findings we propose that inhibition of p38 and ERK activation may be beneficial in reducing inflammatory symptoms in patients with CDI by blocking toxin‐induced TNF‐α release.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.