bluuebunny/crossref_metadata_2025_split huggingface dataset:
AT1 receptor blockade abolishes metabolic and cardiovascular programming effects of neonatal obesity and undernutrition (1085.5)
Authors: Mecawi André , Marangon Paula , Moraes Davi , Bonagamba Leni , Machado Benedito , Elias Lucila , Antunes‐Rodrigues José 
Published: June 2021

The variation of litter size from rodents in the early days of life, which results in neonatal overfeeding or undernutrition, is a very useful model for the obesity study since programs the animals to become obese adults. Moreover, several studies have demonstrated the importance of the angiotensin II (ANG II) in the pathophysiology of obesity and its correlation with cardiovascular diseases. Thus, we aimed to study the role of type 1 ANG II receptors (AT1) on metabolic and cardiovascular effects induced by neonatal obesity or undernutrion programming. For this, the litters were divided into 3 groups: Normal Litter (NL, 10 pups), Small Litter (SL, 3 pups) and Large Litter (LL, 16 pups). The reduction and increment of the litter size increased and decreased , respectively, the body weight (BW) gain in SL (~25%) and LL (~19%) groups, at the weaning (21st day). Despite adult (60 days) SL rats remained with elevated BW, no differences were observed between LL and NL groups. Plasma ANG II levels are higher in both SL (~40%) and LL (~120%) groups in relation to NL at the weaning, with no differences in the adulthood. Both SL and LL groups showed an increase in visceral adipose tissue (~34 and 19%), obesity Lee index (~4 and 3%), and mean arterial pressure (~12 and 10%) in relation to the NL group, respectively. The treatment with losartan (AT1 receptor antagonist) in the drinking water (~ 8 mg / kg / day) from 30 to 60 days of age reduced the visceral adipose tissue weight, Lee index and mean arterial pressure from SL and NL groups. Our data suggest that AT1 receptors are essential for the programming of obesity and hypertension due to neonatal overnutrition or undernutrition.Grant Funding Source: Supported by FAPESP
Autonomic and metabolic changes induced by fructose overload: role of baroreflex (1086.4)
Authors: Santos Fernando , Moreira Edson , Sartori Michelle , Irigoyen Maria 
Published: June 2021

The aim of this experiment was to identify the changes in autonomic and metabolic parameters in a model of metabolic syndrome induced by fructose overload, with focus on the role of baroreflex, as evaluated by sinoaortic denervation. Four experimental groups (rats) were used, followed by 90 days: control(C), denervated control (D), treated with fructose(F) and denervated treated with fructose(DF). The treated groups were submitted to a fructose overload(10%) in drinking water. The caloric intake was higher in F(32%) and DF(18%) groups compared to C, inducing higher body weight gain in F(41%) and DF(27%) when compared to C group. The consumption of D was lower (12%) than the C group as well as body weight gain(8%). The overload of fructose was able to change the fasting plasma glucose baselines values, promoting increasing of glycaemia in both F and DF groups and leading to insulin resistance in the F group. Blood pressure values were also increased in F(17%) and DF(18%) compared to C group. The variability parameters were altered in the three experimental groups (D, F and DF), evidenced by the reduction of the pulse interval variance. Furthermore, the vagal modulation indicators are decreased and blood pressure variability was increased, as expressed by the total variance, in both denervated groups (D and DF). Treatment with fructose was able to induce characteristic changes of metabolic syndrome, such as hypertension, obesity, increased blood sugar and dysautonomia. The absence of the baroreflex was able to mitigate metabolic changes, but when associated with fructose overload caused a greater autonomic dysfunction. The results of the present study indicate a marked influence of baroreflex in the development of metabolic syndrome.Grant Funding Source: Supported by FAPESP 2011/04111‐6
Salt intake during pregnancy influences offspring organ growth (1087.2)
Authors: Peres Maria , de Oliveira Ivone , Furukawa Luzia , Guimarães Carina , Heimann Joel 
Published: June 2021

Introduction: Industrialized food consumption is responsible for high salt ingestion, mainly in western countries. Circulating and tissue renin‐angiotensin system (RAS) activity is influenced by the degree of salt intake. RAS is responsible for blood pressure regulation and hydroelectrolitic balance. High salt intake during gestation may influence the health of adult offspring. As a working hypothesis, the alterations observed in generation F1 may be transmitted to generations F2 and F3. Therefore, in this study some effects of high salt diet during gestation were evaluated in adult male rats of generation F1.Material and Methods: Fifteen adult male Wistar rats, born from mothers fed normal (N group, n=9) or high salt diet (H group, n=6) during the whole gestation, were followed from birth until 15 weeks of age. Body and organs weight (heart, adrenals, kidneys, testicles, epididimes, and retroperitoneal fat), urinary sodium and potassium and creatinine excretion were measured. Daily sperm production and sperm transit time in the epididymal cauda were evaluated by counting homogenization‐resistant testicular spermatids or epididymal spermatozoa, respectively.Results: (mean±SEM)

Parameter
N
H
p value

Body weight (g)
458.78±25.93
438.08±20.91
0.128

Retroperitoneal fat (mg/g)
5.03±2.92
8.24±1.52
0.029

Left testis/body mass (mg/g)
3.50±0.31
3.92±0.30
0.022

Right kidney/body mass (mg/g)
3.21±0.12
3.59±0.17
<0.001

Left kidney/body mass(mg/g)
3.34±0.21
3.60±0.18
0.026

Heart/body mass (mg/g)
3.38±0.23
3.79±0.40
0.024

Sperm production (x106/g/day)
13.05±1.92
12.51±2.65
0.648

Sperm transit time (days)
7.93±0.39
6.99±0.99
0.331

Discussion: Damages on cardiovascular and renal systems caused by high salt intake are well documented and molecular mechanisms are still been studied. Reproductive alterations have been reported, regarding both male and female performance. Our results disclosed higher kidney, heart, testicles and adipose tissue mass in the first generation born from mothers fed high salt diet uring gestation indicating a possible disturbance in organ growth. The difference in testicular mass between the experimental groups was not accompanied by functional alterations.Grant Funding Source: Support by FAPESP (2012/22415‐5, 2012/22801‐2)
Acute hypoxia‐induced endothelial‐dependent suppression of Ca2+ waves in pulmonary arterial myocytes of sheep (1089.14)
Authors: Sandy Scott , Romero Monica , Paez Ricardo , Francis Michael , Taylor Mark , Longo Lawerence , Wilson Sean 
Published: June 2021

Ca2+ responses are important to acute hypoxia‐induced pulmonary arterial contraction. To better understand these signals and the role of functional endothelium we performed confocal imaging of Fluo‐4 loaded pulmonary arterial myocytes of adult sheep using the en‐face preparation. The present studies tested the hypothesis that functional endothelium suppresses resting as well as acute hypoxia (~4%) dependent Ca2+ waves in pulmonary arterial myocytes by examining endothelium intact and denuded arteries. Automated analyses were performed to determine the magnitude and kinetics of the oscillatory Ca2+ responses. Endothelium removal decreased the amplitude and area under the curve (AUC) of Ca2+ waves but did not significantly impact the duration, or the rate of rise and fall. Acute hypoxia in endothelium intact arteries suppressed the Ca2+ amplitude, AUC, as well as the duration, and rate of rise and fall. However, endothelium removal prevented these acute hypoxia‐induced reductions in the magnitude and kinetics of the Ca2+ responses. These data illustrate that functional endothelium suppresses pulmonary arterial myocyte Ca2+ responses in resting conditions and in response to acute hypoxia, an effect that could influence either excitation‐contraction or excitation‐transcription coupling.Grant Funding Source: Supported by MRI923559, NIH R03HD69746, R01HD31226, R01HD3807, P20MD6988 and LLUSOM
ASIC1‐dependent Ca2+ influx is required for NFATc3 activation in chronic hypoxia‐induced pulmonary hypertension (1090.12)
Authors: Jernigan Nikki , Plomaritas Danielle , Giermakowska Wieslawa , Herbert Lindsay , Nitta Carlos , Gonzalez Bosc Laura 
Published: June 2021

The development of chronic hypoxia (CH)‐induced pulmonary hypertension is associated with 1) the activation of the Ca2+‐dependent transcription factor, nuclear factor of activated T‐cells isoform c3 (NFATc3), and 2) enhanced acid sensing ion channel 1 (ASIC1)‐dependent Ca2+ influx in pulmonary arterial smooth muscle cells (PASMC). Therefore, we hypothesize that ASIC1‐mediated Ca2+ influx increases NFATc3 nuclear translocation in pulmonary vascular smooth muscle. To test this hypothesis we first examined the effect of ASIC1 inhibition on NFATc3 nuclear translocation in PASMC in response to endothelin‐1 (ET‐1; 10‐7 M). Inhibition of ASIC1 with psalmotoxin‐1 (20 nM) diminished ET‐1 induced Ca2+ influx and NFATc3 nuclear import. In addition, ET‐1 mediated pulmonary arterial vasoconstriction and Ca2+ influx following CH (1 wk @ 380 mmHg) were blunted in ASIC1 knockout mice (ASIC1‐/‐) compared to the ASIC1 wildtype mice (ASIC1+/+). Similarly, CH increased pulmonary vascular smooth muscle NFATc3 nuclear translocation in ASIC1+/+ mice, but not in ASIC1‐/‐ mice. These CH‐induced responses were additionally associated with decreased right ventricular systolic pressure and right ventricular hypertrophy in ASIC1‐/‐ mice. Taken together, these data suggest that ASIC1‐dependent Ca2+ influx is required for the activation and nuclear translocation of NFATc3 during the development of pulmonary hypertension.Grant Funding Source: Supported by R01 HL92598, R01 HL111084, T32 HL07736, R01HL088151, R01 HL088192
Microparticles stimulated by hypoxic pulmonary hypertension have differing effects on vascular cell growth than microparticles from severe occlusive pulmonary arterial hypertension (1090.7)
Authors: Yarbrough Thomas , Bauer Natalie 
Published: June 2021

The release of microparticles (MPs), intact, sub‐micron vesicles containing signaling molecules such as proteins, lipids, mRNAs, and miRNAs, is significantly increased in pulmonary arterial hypertension (PAH). MPs contribute to vascular cell proliferation, and the mechanism of increased proliferation in the arteriopathy of PAH is still unclear. Thus, we propose that circulating MPs from pulmonary hypertensive rats will stimulate pulmonary microvascular endothelial (PMVEC) and/or pulmonary artery smooth muscle cell (PASMC) proliferation. PMVECs and PASMCs were treated with MPs from controls, 3 wk hypoxia only (Hx) rats, or 3 wk Su/Hx/Nx rats. Interestingly, although the Su/Hx/Nx model shows severe vascular remodeling, MPs from the hypoxic rat had the most significant effects on PASMC proliferation by shifting the log phase of growth. Western blot analysis shows corresponding changes in smooth muscle cell markers. PMVECs were treated similarly with 5 wk MPs from the Su/Hx/Nx progressive model, resulting in a shift of log growth phase. Our data suggest that circulating MPs isolated from 3 wk Hx‐treated rats may signal to PASMCs to increase proliferation, whereas MPs from a severe occlusive model of PAH stimulate changes in proliferation rates of PMVECs. Combined these data suggest that hypoxic pulmonary hypertension and severe occlusive PAH result in different signaling MPs with unique vascular cell effects.Grant Funding Source: Supported by NHLBI T32 HL076125 to TMY and AHA 11SDG7390037 to NNB.
Ventilatory chemoreflex sensitivity in sleep apnea is decreased with high dose ascorbic acid (1092.13)
Authors: Leuenberger Urs , Aswegen Caleb , Blaha Cheryl , Mast Jessica 
Published: June 2021

Obstructive sleep apnea (OSA) is associated with increased sympathetic activity, hypertension and augmented activity of the arterial chemoreflex. To test the hypothesis that oxidative stress, presumably due to intermittent hypoxia, contributes to these abnormalities, we determined blood pressure (BP), heart rate (HR), muscle sympathetic nerve activity (MSNA, peroneal microneurography), minute ventilation (MV) and the responses to 2‐8 breaths of nitrogen (N2, 10 trials aiming for O2 saturation nadirs of 70‐90% [SpO2, oximetry]) before and after infusion of the antioxidant ascorbic acid (AA, 45 mg/kg over 20 min, followed by 15 mg/kg over 1 hr) in 8 patients with OSA (age 49±4 yrs, 7 male/1 female, apnea‐hypopnea‐index 42±10 events/hr). While AA did not affect BP (pre vs. post: 89±2 vs. 90±3 mmHg; P=NS), HR (pre vs. post: 67±5 vs. 66±4 beats/min; P=NS), MSNA (pre vs. post: 48±4 vs. 45±3 bursts/min; P=NS) and MV (pre vs. post: 11.1±0.8 vs. 11.6±0.9 L/min; P=NS), the ventilatory responses to N2 induced transient hypoxia (expressed as the slope of peak MV vs. SpO2 nadir) decreased from ‐0.372±0.059 pre‐AA to ‐0.288±0.058 L/min/%SpO2 post‐AA (P<0.05). Thus, ventilatory chemoreflex sensitivity which is thought to be enhanced in OSA decreases after AA. This suggests that the enhanced chemoreflex activity in patients with OSA is at least in part due to oxidative stress.Grant Funding Source: Supported by P01 HL096570 and UL1 TR000127
The role of miR‐21 in propofol‐induced neurotoxicity in developing human neurons (1093.2)
Authors: Twaroski Danielle , Bai Xiaowen , Olson Jessica , Yan Yasheng , Liu Yanan , Bosnjak Zeljko 
Published: June 2021

Recent studies in animal models have suggested that anesthetics such as propofol, when administered early in life, can lead to neurotoxicity. These studies have raised safety concerns regarding the use of anesthetics in the pediatric population. Human embryonic stem cells (hESCs) are capable of differentiating into any cell type and represent a promising model by which to study mechanisms governing anesthetic‐induced neurotoxicity in humans. In this study, we assessed the effects of propofol on hESC‐derived neurons and the role of microRNAs (miRs) in the toxicity observed.hESCs were differentiated into neurons following a four‐step differentiation protocol. Cell death in the hESC‐derived neurons was assessed using TUNEL staining and microRNA expression was assessed using qRT‐PCR. miR‐21 was overexpressed using a miR‐21 mimic and the expression of the miR‐21 targets of interest was assessed by Western blot.Exposure to 20 µg/mL propofol for 6 hours induced significant cell death in the hESC‐derived neurons and downregulated several microRNAs, including miR‐21. Overexpression of miR‐21 significantly attenuated the increase in cell death following propofol administration. In addition, several targets within the miR‐21 pathway (eg. Sprouty 2 and pSTAT3) were significantly altered by propofol exposure, suggesting that miR‐21 is contributing to the propofol‐induced neurotoxicity.Grant Funding Source: Supported by P01GM066730 and R01HL034708 (NIH) and FP00003109 (Advancing Healthier Wisconsin) to ZJB
TRPC channels are involved in endothelin 1 mediated inhibition of renin release from juxtaglomerular cells (1095.12)
Authors: Ortiz‐Capisano M. Cecilia 
Published: June 2021

Renin is produced by, stored in and released by juxtaglomerular (JG) cells. Increases in intracellular calcium (Ca) decrease renin release. I’ve found that JG cells contain multiple isoforms of canonical transient receptor potential (TRPC) Ca‐permeable channels. Among those, TRPC1, 4 and 5, are known to function as store‐operated Ca channels. Endothelin (ET)1 binds to G‐coupled protein receptors whose activation leads to a phospholipase C (PLC)/ IP3 signaling pathway, potentially stimulating store‐operated Ca channels. I hypothesized that endothelin inhibits renin release by activating TRPC store‐operated Ca channels. RT‐ PCR revealed expression of both ETA and ETB receptors in freshly isolated mouse JG cells. Incubation of primary cultures of JG cells with ET1 (10nM) decreased renin release by 28% from 0.84±0.07 to 0.60±0.07 µg ANGI/ml/hr/mg prot. (p<0.001). An IP3 blocker (2APB, 0.1mM) returned renin release back to control. Addition of the TRPC blocker (SKF 96365, 50µM) completely reversed the Ca‐mediated inhibition of renin release by ET1 to 0.99±0.07 µg ANGI/ml/hr/mg prot. These results suggest that 1) JG cells express ETA and ETB receptors, 2) ET1 mediates inhibition of renin release in JG cells by activation of ETA or ETB receptors and subsequent PLC/IP3 signaling cascade activation, and 3) ET receptors link ET1 and TRPC store‐operated Ca channels to mediate ET1‐mediated Ca inhibition of renin release.Grant Funding Source: NIH 5PO1HL090550‐03
Lipopolysaccharide‐induced inflammation is associated with receptor for advanced glycation end products in human endothelial cells (1096.5)
Authors: Wang Liqun , Chen Tangting , Wu Jianbo , Huang Qiaobing 
Published: June 2021

The vascular endothelium is the center of events leading to the development of inflammatory lesions. The activation of endothelial cells is of significance in acute as well as chronic inflammatory states such as septic shock and atherosclerosis, respectively. Receptor for advanced glycation end products (RAGE) plays a role in immune reaction to recognize specific molecular patterns as pathogen recognition receptors. However, the function of RAGE in LPS‐induced inflammation is unclear. In this study, we investigated whether RAGE is enrolled in lipopolysaccharide (LPS)‐induced cell activation in human umbilical vein endothelial cells (HUVECs) using a combination of western blotting, confocal microscopy, and functional assays. We found that LPS can directly increase the expression of RAGE in a time‐ and concentration‐ dependent manner. And anti‐RAGE antibody inhibited LPS‐mediated barrier high‐permeability and apoptosis of HUVECs. Furthermore, LPS‐induced NF‐κB activation and IκBα degradation was also significantly attenuated by anti‐RAGE antibody. Given these results, RAGE plays an important role in LPS‐induced inflammation and could be a candidate as a therapeutic target for various systemic inflammatory diseases.Grant Funding Source: AHA
Glucose infusion increases mRNA expression of deiodinase 1 &amp; 2, and thyroid hormone receptor β‐1 in a fasting‐adapted mammal (1101.12)
Authors: Martinez Bridget , Soñanez‐Organis José , MacKenzie Duncan , Crocker Daniel , Ortiz Rudy 
Published: June 2021

Food deprivation in mammals is typically associated with reduced glucose, thyroid hormone (TH) concentrations and deiodinase (DI) content and activity to suppress metabolism. However, in prolong‐fasted, metabolically active elephant seal pups, the hypothalamic‐pituitary‐thyroid axis (HPT axis), which is responsible for the production of TH, is up‐regulated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food‐deprived mammals. To address our hypothesis that increased glucose increases peripheral TH receptor beta‐1 (THrβ‐1) mRNA expression and content in prolong‐fasted pups, we assessed the cellular TH‐mediated response to a glucose challenge by measuring TH profiles during a glucose tolerance test (GTT) and comparing the changes in profiles in early and late fasted pups. THrβ‐1 mRNA expression increased 59% ± 24 and 336% ± 95 by the 60 and 120 minute mark, respectively. Protein expression of THrβ‐1 also increased during the GTT, 40% ± 4 and 80% ± 23 at 60 and 120 minutes, respectively. mRNA expression of DI1 and DI2 increased by the 120 minute time point, 100% ± 34 and 400% ± 63, respectively. The data suggests that cellular TH pathways are responsive to changes in glucose, which in turn maybe regulated by TH. This suggests that the HPT axis is active and functional during prolonged food‐deprivation in metabolically and physically active mammals.Grant Funding Source: Supported by NIH/NHLBI 442606‐RO‐29013
Role of body composition and circulating hormones on resting energy expenditure in obese pregnant women (1101.9)
Authors: Perez‐Rodriguez Marcela , de Haene Jessica , Castañeda Diana , Stotland Naomi , Murphy Elizabeth , Talavera Juan , Havel Peter , King Janet 
Published: June 2021

The extra energy required for synthesis and maintenance of new tissue increases the REE during pregnancy. The net change may vary 8‐fold with higher increases seen in obese than non‐obese women. Our objective was to identify body composition and hormonal factors influencing the REE of obese women during the last half of pregnancy. A total of 64 women with BMI >25 kg/m2 , 18‐42 years of age, and no history of chronic disease were recruited at 20 weeks gestation. Three were eliminated due to extreme obesity (BMI=53 kg/m2) and 2 for missing values giving a total of 59 participants. REE, body composition, and insulin resistance (HOMA‐IR), prolactin, progesterone, estradiol, leptin, adiponectin, and IGF‐1 were measured at 20, 28, and 34 weeks gestation. During the 14‐wk study, the REE increase averaged 200 kcal/d. The change varied from a 400 kcal/d decrease to a 590 kcal/d increase. Multivariant models predicted 62% of the variability in REE at 20 weeks, 41% at 28 and 34 weeks, and 24% of the change in REE from 20 to 34 weeks. Significant determinants varied with time of pregnancy: FM, FFM, progesterone and prolactin at 20 wks; FM and FFM at 28 wks; FM, FFM, and IGF‐1 at 34 wks; and FFM and IGF‐1 change predicted the REE change from 20 to 34 wks. Body composition and metabolic hormones only explained 24 to 60% of the REE variability in obese pregnant women suggesting that other factors play a role.Grant Funding Source: NIH Grant R01HD46741.
Neutrophil accumulation after contraction‐induced muscle injury is dependent upon P‐ and E‐selectin (1102.13)
Authors: Sloboda Darcee , Brooks Susan 
Published: June 2021

Neutrophils accumulate in skeletal muscle after contraction‐induced injury and are thought to exacerbate damage to muscle fibers. The mechanism by which neutrophils enter the muscle is not known, but adhesion proteins on vascular endothelial cells may play a role. We tested the hypothesis that the adhesion proteins P‐ and E‐selectin are critical for neutrophil accumulation after contraction‐induced injury and that blunting neutrophil accumulation would reduce damage. To test our hypothesis, we injured mouse muscles in situ with a series of lengthening contractions. Mice were injected with either antibodies that block P‐ and E‐selectin or control antibodies. In control muscles, injury caused a 50% force deficit, overt damage to muscle fibers and a 15‐fold increase in neutrophil content after two days. Mice treated with blocking antibodies to P‐ and E‐selectin showed a decrease in neutrophil content but no change in force deficit or damage to muscle fibers. Our data suggests that neutrophil accumulation after contraction‐induced injury is dependent upon P‐ and E‐selectin but that blunting neutrophil infiltration after contraction‐induced injury does not always reduce damage.Grant Funding Source: AG000114