bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are lymphatic contractions initiated and/or coordinated by ICC‐like cells in the lymphatic vessel wall?
Authors: Davis Michael J. , Castorena‐Gonzale Jorge , Li Min , Gui Peichun , Domeier Timothy L. , Zawieja Scott 
Published: June 2021

Lymph propulsion relies critically on the spontaneous contractions of collecting lymphatic vessels, which are surrounded by smooth muscle cells (LMCs). Twitch‐like contractions are generated by an intrinsic ionic pacemaker that is assumed to originate in the LMC; however there are reasons to consider that pacemaking might be initiated and/or coordinated by a network of specialized cells. Precedents include interstitial cells of Cajal (ICC) in the GI tract and ICC‐like cells (ICC‐LC) in other smooth muscle‐invested organs, which are known to initiate pacemaking. ICCs express the receptor tyrosine kinase c‐Kit, and c‐Kit(+) cells have been identified in the lymphatic wall, although their function is unknown. We used existing and newly‐generated mouse models to test the hypothesis that ICC‐LCs control lymphatic pacemaking. In addition to c‐Kit, we considered PDGFRa, a receptor expressed by some ICC‐LCs. Our strategy was to use Cre lines specific for four cell types (c‐Kit‐ or PDGFRa‐expressing cells, pericytes, LMCs) and: 1) cross them with reporter mice to identify the recombined cell populations in the lymphatic wall; 2) use them to express the endogenous Ca2+ indicator GCaMP6f in the respective cell types and correlate Ca2+ signals with the lymphatic contraction cycle; 3) express the photo‐activated cation channel ChR2 in the respective cell types and test the consequences of triggering ChR2 activation. Rounded c‐Kit(+) cells were associated with the outer adventitia and co‐stained for mast cell markers. GCaMP expression revealed Ca2+ signals that did not oscillate with the contraction cycle, but responded robustly to a mast cell degranulator. PDGFRa cells formed a partial sheath of oak‐leaf shaped cells outside of the medial layer—characteristics of adventitial fibroblasts; they did not exhibit spontaneous Ca2+ oscillations, but occasional cells responded to ACh. A reputed pericyte‐specific Cre, Ng2CreERT2, produced recombination in about 50% of LMCs, some neurons, some spindle‐shaped cells in the wall, and a subpopulation of PDGFRa(+) cells. Expression of GCaMP under this Cre revealed Ca2+ oscillations in LMCs and spindle‐shaped cells at the same frequency as spontaneous contractions. Expression of GCaMP only in LMCs using SmmhcCreERT2 revealed synchronized Ca2+ signals in synchrony with and preceding spontaneous lymphatic contractions. Expression of ChR2 using the same Cre, followed by photo‐stimulation of single LMCs, triggered contractions that were consistently entrained over the entire vessel. Although we cannot exclude a role for pericytes due to the promiscuous recombination by Ng2CreERT2, our results suggest that LMCs are the only cell type responsible for lymphatic pacemaking in the mouse.Support or Funding InformationNIH HL‐122578This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Decline in conduit artery function across the healthy human adult lifespan: influence of successful aging
Authors: Shields Katherine , Broxterman Ryan , Kwon Oh Sung , Park Sounghun , Jarrett Catherine , Smith Ken , Wray D Walter , Richardson Russell 
Published: June 2021

While it is well‐established that vascular function decreases with age, potential differences in this decay between typical aging (≈ 70 yrs, many unlikely to become centenarians) and highly successful aging (>90 yrs, with preserved physical and cognitive health) remain unknown. Therefore, this study measured brachial artery flow‐mediated dilation (FMD) in 42 young (YA, 25 ± 7 yrs), 45 old (OA, 71 ± 7 yrs), and 16 oldest old (OOA, 96 ± 4 yrs) healthy adults. FMD was significantly lower in OA (5.4 ± 2.7 %) and OOA (4.5 ± 2.3%) than YA (7.7 ± 4.0 %), with no difference between OA and OOA, despite the ≈25 yr age difference. Across all age groups, a significant relationship between age and FMD was detected with a two‐segment linear model, identifying a significant change in the rate of FMD decline with age at 97 yrs (slope 1 = −0.040, slope 2 = −0.528 %/yr; r = 0.38). Utilizing this break point of 97 yrs, the OOA were further refined into OOA (93 ± 2 yrs, n = 10) and centenarians (CA, 99 ± 1 yrs, n = 6), with FMD significantly lower in CA (3.2 ± 1.4 %) than OOA (5.3 ± 2.4 %). These findings reveal a steady decline in conduit artery function across the human adult lifespan. However, of importance, successful aging serves to diminish the rate of decline in conduit artery function across the majority of the lifespan until >97 yrs of age, when this decline is greatly exacerbated.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Angiogenesis is Not Impaired in Cultured Rat Mesenteric Microvascular Networks
Authors: Hodges Nicholas A. , Murfee Walter 
Published: June 2021

Angiogenesis is commonly assumed to be impaired in aged tissues. However, this preconception is challenged by evidence of increased angiogenesis during cancer and other pathological scenarios prevalent in aged models. In addition, the cumulative evidence from the literature remains non‐definitive. Hence, fundamental questions remain regarding the mechanisms by which angiogenesis is affected in aged tissues. The objective of this study was to compare the angiogenic responses in aged versus adult rat mesenteric cultured tissues. Adult (9 month) and Aged (24 month) male Wistar rat mesenteric tissue were harvested and cultured for 3 days per media group: 1) minimum essential media (MEM), 2) MEM with 10% fetal bovine serum (FBS), and 3) MEM with basic fibroblast growth factor (bFGF) (minimum of n = 8 tissues from 4 rats per group). After culture tissue microvessels were identified by PECAM labeling. FBS and bFGF stimulation induced an increase in the number of capillary sprouts per vascular area in the Adult (MEM = 2.14 ± 0.374 sprouts/mm2; FBS = 4.44 ± 0.595 sprouts/mm2; bFGF = 4.80 ± 0.447 sprouts/mm2; p < 0.05) and Aged (MEM = 3.12 ± 0.520 sprouts/mm2; FBS = 5.48 ± 0.609 sprouts/mm2; bFGF 5.98 ± 0.563 sprouts/mm2; p < 0.05) tissues compared to age group matched MEM only tissues. Capillary sprouting was not significantly different between the FBS stimulated aged and adult tissues (p = 0.216). Similarly, sprouting in the bFGF stimulated aged and adult tissues were not significantly different (p = 0.125). These results suggest that angiogenesis in aged tissues can be stimulated comparable to adult levels and that angiogenesis is not necessarily impaired.Support or Funding InformationFunded by NIH R01AG049821.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Echocardiographic assessment of G‐protein coupled estrogen receptor (GPER) activation on coronary blood flow and cardiac function in mice
Authors: Yu Xuan , Guo Shaodong , Han Guichun 
Published: June 2021

G protein coupled estrogen receptor (GPER) has been reported to have cardiovascular protective effects in animal models and human tissues. Our previous work also showed that activation of GPER induced porcine coronary artery relaxation. In this study, we used non‐invasive high resolution echocardiography to evaluate the in vivo effects of GPER on coronary blood flow (CBF) of left coronary artery and cardiac functions in C57BL/6 male mice. Animals were anesthetized with 3% isoflurane in 100% oxygen and anesthesia was maintained with 1% isoflurane. In this echocardiographic studies, pulse wave Doppler imaging and M mode Doppler imaging were performed to measure CBF, left anterior descending coronary artery diameter and cardiac function parameters. CBF was calculated by measuring coronary artery diameter and velocity time integral in pulse wave Doppler. Cardiac function parameters including heart rate (HR), stroke volume (SV), cardiac output (CO), ejection fraction (EF), end diastolic volume (EDV) and end systolic volume (ESV) were calculated by tracing the left ventricle long axis in M mode Doppler. Intraperitoneal injection of G‐1 (3 mg/kg) significantly increased CBF from 1.68 ± 0.1 mL/min to 2.37 ± 0.2 mL/min. G‐1 injection on the cardiac function parameters showed biphasic responses. Within the first two minutes of G‐1 injection, HR (from 423 ± 15 bpm to 563 ± 12 bpm) and EF (55% % to 77 %) were increased; while EDV (from 34 ± 3.5 μl to 18 ± 1.2 μl), ESV (from 15 ± 1.9 μl to 4 ± 1.1 μl) and SV (from 19 ± 1.8 μl to 14 ± 1.5 μl) were decreased. After two minutes of G‐1 injection, cardiac responses reversed. HR (from 563 ± 12 bpm to 399 ± 8 bpm) and EF (from 77 % to 56 %) were decreased; while EDV (from 18 ± 1.2 μl to 38 ± 2.2 μl), ESV (from 4 ± 1.1 μl to 10 ± 1.2 μl) and SV (from 14 ± 1.5 μl to 20 ± 2.6 μl) were increased. These findings demonstrated that activation of GPER showed biphasic responses that initial activation of GPER exerted a positive chronotropic effects, and then the chronotropic effect became negative, with a positive inotropic effects on both systolic and diastolic functions in mice. In conclusion, we revealed that GPER activation increases coronary blood flow and induces biphasic responses on cardiac functions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kvβ2 Subunit Regulates Cardiac Levels of SLC41a3 a Sodium‐Magnesium Transporter.
Authors: Tur Jared , Chapalamadugu Kalyan C. , Tipparaju Srinivas M. 
Published: June 2021

BackgroundClinical evidence has demonstrated that administration of magnesium can provide cardioprotective benefits during acute MI as well as suppression of cardiac arrhythmias. Further, meta‐analysis data has uncovered an inverse relation to circulatory levels of magnesium and risk for cardiac injury. Magnesium influx/efflux behaviors have been recorded in isolated cardiomyocytes; further the addition of magnesium during and prior to cardiac injury such as ischemia reperfusion was demonstrated to significantly reduce ischemic injury. While clinical evidence highlights magnesium's cardiovascular benefits, identification and subsequent regulation remain largely unknown of the magnesium channels responsible. Recent research has identified one of the key magnesium/sodium exchange channels as SLC41a1‐3 family. Murine cardiac expression levels demonstrate significant mRNA levels of SLC41a3 in particular.Methods and ResultsA recent microarray study performed in hearts from Kvβ2 knockout mice demonstrated a significant decrease in SLC41a3 mRNA expression compared with control. Protein expression validated the decrease in expression levels of SLC41a3. These findings may indicate the Kvβ2 subunit acts as a novel regulator to SLC41a3, previous research identified Kvβ2 having protein‐protein interactions with SLC39a1 another member of the solute carrier family (SLC). Cardiac function measured by monophasic action potential (AP) recordings presented with a significant reduction in AP duration values in control hearts perfused with magnesium (MgSO4) while Kvβ2 KO hearts demonstrate little to no alterations in AP duration post magnesium exposure. Further functionality will be assessed in isolated cardiomyocytes testing the influx and efflux of magnesium to understand Kvβ2's role in channel activity.HypothesisBased upon our preliminary data we hypothesis that the Kvβ2 subunit plays significant roles in SLC41a3 expression as well as function within the heart.ConclusionThese novel roles of Kvβ2 may shed new light on the molecular understanding of how administration of magnesium can benefit both cardiac injury and arrhythmias.Support or Funding InformationResearch Supported: This Research work was funded by National Institutes of Health (NIH) Grant R01‐HL‐102171 (S. M. Tipparaju).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Study of Vascular and Endothelial Function in Type II Diabetes with Newly Diagnosed
Authors: Srivastava Prachi , Chandran Dinu S. , Jaryal Ashok Kumar S. , Jyotsna Viveka P. , Deepak Kishore Kumar S. 
Published: June 2021

BackgroundHigh risk of cardiovascular and cerebrovascular diseases are associated with diabetes and this risk is augmented with coexistent hypertension. Increased arterial stiffness and endothelial dysfunction are independent risk factors and predictor of adverse cardiovascular outcome. Angiotensin converting enzyme inhibitors (ACE inhibitors) have been prescribed for the hypertension treatment and are known to reduce cardiovascular mortality and morbidity.ObjectiveTo study the effect of ACE inhibitor on vascular and endothelial function in type 2 diabetes with newly diagnosed hypertension.MethodsSixty‐five diabetic patients with newly diagnosed hypertension with the mean age of 48 ± 6.5 years were enrolled in the study. The mean duration of diabetes and BMI was 6.01 ± 5.03 years and 28.18 ± 4.23 kg/m2, respectively. Arterial stiffness was assessed using Augmentation index (AIx@75) and Pulse Wave Velocity (PWV) [carotid‐radial (cr), and carotid‐femoral (cf)] by applanation tonometry using SphygmocorR. Endothelial function was assessed by flow mediated dilatation (FMD) using B‐mode vascular ultrasound. All the recordings were done at baseline, after 1 week and after 3 Months of ACE inhibition.ResultsBoth Peripheral and central blood pressures (systolic, diastolic and pulse pressure) were reduced significantly after ACE inhibition (p <0.0001). There was significant reduction in AIx@75 after 1 week of ACE inhibitor treatment as compared to baseline (25.86 ± 10.01 vs 20.85 ± 10.06 %, p<0.0001). cr and cf PWV were significantly decreased from baseline to after 1 week of treatment [9.15 ± 1.64 Vs 8.32 ± 1.52 m/s (p<0.0001) and 11.3 ± 2.84 Vs 10.38 ± 3.08 m/s (p<0.05) respectively] and from baseline to after 3 months of ACE inhibitor treatment [9.15 ± 1.64 Vs 8.16 ± 1.53 m/s, (p<0.0001) and 11.3 ± 2.84 Vs 9.78 ± 2.98 m/s (p=0.0002), respectively]. Similarly, FMD was significantly increased after 1 week and 3 months of ACE inhibition as compared to baseline [6.1 ± 3.2 Vs 8 ± 3.11%, and 6.29 ± 3.27 Vs 9.99 ± 3.17% (p<0.0001)]. There was further improvement in FMD from 1 week to 3 months of ACE inhibition [8 ± 3.11 Vs 9.99 ± 3.17% (p<0.0001)].ConclusionBoth arterial stiffness, including central pressures and endothelial function improved within 1 week of ACE inhibition. Endothelial function further improved after 3 months of ACE inhibition in type II diabetic patients with newly diagnosed hypertension. This could be because of ACE inhibitor mitigates the effect of angiotensin II on endothelium and vascular smooth muscles.Support or Funding InformationAll India Institute of Medical Sciences, New Delhi, India.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 Endothelin‐Related Gene Polymorphisms on Age‐Related Arterial Stiffening: A 10‐Year Longitudinal Study
Authors: Sugawara Jun , Tomoto Tsubasa , Noda Naohiro , Matsukura Satoko , Tsukagoshi Kazuya , Maeda Seiji 
Published: June 2021

Increased arterial stiffness has emerged as a strong predictor of future cardiovascular events and all‐cause mortality. The aim of this study was to elucidate influences of endothelin (ET)‐related genetic polymorphisms on age‐related arterial stiffening through a 10‐year longitudinal study. A decadal change in brachial‐ankle pulse wave velocity (baPWV), an index of arterial stiffness, was evaluated retrospectively among 92 volunteers (63 ± 14yrs, 51 men). The targeted single‐nucleotide polymorphisms were ET‐A receptor SNP rs5333 (ET‐A) and ET‐B receptor SNP rs5351 (ET‐B). Subjects with either ET‐A TC or CC genotypes exhibited significantly greater increases in baPWV (+15.3 ± 11.7 and +16.6 ± 15.7%/dec, respectively) than ET‐A TT genotype holders (+9.2 ± 9.0%/dec), while subjects with the ET‐B GG genotype showed a significantly greater increase in baPWV (+17.7 ± 14.1%/dec) than other ET‐B genotype holders (AA: +9.5 ± 10.0%/dec; AG: +11.2 ± 9.6%/dec). The combination of these ET‐related genetic risks was associated with a 2.4 times greater decadal increase in baPWV compared with no genetic risk (+8.1 ± 8.4 vs. 19.5 ± 16.0%/dec). These differences remained significant after adjusting for confounding factors, including baseline baPWV. Our current longitudinal study found that ET‐related gene polymorphisms contribute to diverse age‐related changes in arterial stiffness.Support or Funding InformationThis study was supported by special coordination funds of the Japanese Ministry of Education, Culture, Sports, Science, and Technology (KAKENHI JP25702045 and JP26670116, to JS).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Changes in CRP and TNF‐a after Runs at Different Intensities in Smokers Following Two Hour Cessation
Authors: Dao Vivian , Nickerson Brett Stephen , Park Kyung‐Shin 
Published: June 2021

The purpose of this study was to examine changes in C‐reactive protein (CRP) and TNF‐α from blood samples before and after exercise at different intensities in smokers (SM) and non‐smokers (NS) after a 2 hour smoking cessation. Our laboratory previously reported large differences in CRP and TNF‐α at Pre between SM and NS. Furthermore, there were more profound disturbances in SM following three runs at different intensities approximately 30 minutes after smoking cessation before each run (EB 2015, Boston). The previous findings indicated that SM responded more sensitively to relatively equal intensity of exercise, which suggested that high intensity aerobic exercise should be avoided in SM in the beginning phase of exercise training.MethodsA total of eighteen physically inactive subjects (eight SM and ten NS) aged 20 to 27 were recruited. Smokers were accepted if their level of exhaled carbon monoxide (eCO) was greater than 16 ppm. Each subject completed three treadmill runs at different intensities in a random order (55%, 65%, and 75% of VO2max). Running distance for all three runs was equivalent to 35‐min run at 65% VO2max. Smokers had a 2 hour smoking cessation before each run. Blood samples were collected before (Pre), immediately post (IP), and an hour following each run (1h Post).ResultsPre‐exercise CRP levels were higher in SM as compared to the NS. (2.291±.27 mg/L Vs. 2.082±.25, mean±SE, P = 0.042). As compared to Pre, no significant changes were found in CRP at IP and 1h Post following runs at three different intensities in both SM and NS. TNF‐α showed higher pre‐exercise levels in SM compared to NS (32.565±4.28 mg/L vs. 27.732±3.34, P=0.027). TNF‐α was significantly increased at IP following 75% of VO2max run in both SM and NS (SM: 32.657±4.36 → 38.797±6.33, P=0.013; NS: 27.694±3.26 → 33.466±4.35, P=0.019), but not significantly changed at IP following 55% and 65% of VO2max runs.ConclusionFindings of the current study revealed a dose‐response relationship for CRP and TNF‐a in SM and NS. The patterns of changes corresponded with previous presentation (EB, 2015) with a 30 minute smoking cessation; however, the differences between SM and NS were much smaller in this study suggesting that smokers may need to avoid cigarette smoking before exercise to minimize immune disturbance caused by combined stress from exercise and chronic smoking.Support or Funding InformationThis study was supported by Texas A&M International University Research 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.
Effects of acute loaded wheel running on BDNF expression in the rat hippocampus
Authors: Lee Min Chul , Cha Joo Eu , Yoo Tae Woo 
Published: June 2021

Voluntary wheel running has beneficial effects on hippocampal cognitive functions if done abundantly. However it is still uncertain whether resistance wheel running would be the same. Voluntary resistance wheel running with a load is a suitable model, since it allows increased work levels and resultant fast‐twitch muscular adaptation. Here we examined whether acute voluntary wheel running with an additional load on BDNF expression in the rat hippocampus. We used 10‐week‐old male Wistar rats and divided randomly into sedentary (Sed), voluntary exercised with No‐load 3) voluntary exercised with additional Load group for acute 1 week. The load for the Load group was increased to reach ~30% of body weight during training. The expression of BDNF genes was quantified by realtime PCR. The relative soleus weights were greater in the No‐Load group. Further, loaded wheel running up‐regulated gene expressions in BDNFmRNA level compared with the Control group. Interestingly, BDNFmRNA levels showed a positive correlation with work load levels(r=0.75), supporting the idea that work levels availability contributes to the BDNF benefits of loaded wheel running revealed in this study. Overall, this novel approach assessing the first time that voluntary loaded wheel running which causes a muscular adaptation, resulted in enhanced gene expression of BDNF, suggesting a possible role of high‐intense short term exercise on hippocampal BDNF actions.Support or Funding InformationThis work supported by the National Research Foundation of Korea Grant funded by the Korean Government (NRF‐201700310001).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.