bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Vasoconstriction and Vascular Remodeling Play Role in Reactive Pulmonary Hypertension in Rats
Authors: Odintsov Igor , Chovanec Milan , Banasova Alena , Hampl Vaclav , Herget Jan 
Published: June 2021

IntroductionThe majority of clinical cases of pulmonary hypertension (PH) are caused by left heart failure. Some patients with venous PH induced by left heart pressure overload develop increase in resistance in the arterial part of the pulmonary circulation (reactive PH). We developed a new animal model of reactive PH caused by left heart pressure overload. We tested hypothesis that pulmonary arterial vasoconstriction and/or pulmonary vascular remodeling play role in our rodent model of reactive PH.MethodsLeft heart pressure overload was induced in adult male Wistar rats by partial intravascular obstruction of the ascending aorta. Three weeks later the experimental rats (group E, n=6) were compared to controls (group C, n=7). In isolated lungs perfused with salt solution with albumin we studied hemodynamic changes in pulmonary circulation by analysis of perfusion pressure increments induced by increasing perfusion flow (P/Q relationship). The P/Q relationship measurement was repeated after adding sodium nitroprusside into perfusate to reveal presence of pulmonary arterial vasoconstriction. In lung histology we counted remodeled peripheral pulmonary vessels in the group E compared to controls.ResultsThe slope of the P/Q relationship was significantly increased in the group E compared to controls (0.112±0.003 mmHg.mL−1.min−1 vs. 0.0046±0.002 mmHg.mL−1.min−1; p<0.0001). Sodium nitroprusside did not alter the slope in controls (0.043±0.002 mmHg.mL−1.min−1). In the group E, sodium nitroprusside reduced the slope to a value not different from that in controls (0.044±0.001 mmHg.mL−1.min−1). In lung histology, 74 % of the small pulmonary vessels had muscularized media in the group E, compared to only 24 % in controls (p<0.01).ConclusionPulmonary vasoconstriction and pulmonary vascular remodeling are involved in the new model of reactive pulmonary hypertension in rats.Support or Funding InformationGrants: GAUK 210216 and GACR 17‐11223SThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
On the Mechanism of Flow Sensing by Guinea Pig Carotid Endothelial Cells
Authors: Espinosa‐Tanguma Ricardo , Hernández‐Méndez Aurelio 
Published: June 2021

It is known that luminal facing endothelial G‐protein coupled receptors (GPCRs) are affected by flow. In human blood vessels bradykinin produces a relaxing effect whereas in guinea pig its effect is vasoconstrictive and affected by flow.Objetiveto study the mechanism by which flow is sensed by endothelial cells.Methodswe have used guinea pig carotid arteries to evaluate the effect of flow on the contractile response to bradykinin and cultured carotid endothelial cells to know the expression pattern of p‐SRC and p‐ERK in response to flow.ResultsWe have found that in guinea pig carotid artery the flow‐dependent vasoconstrictive effect of bradykinin is augmented by 5 min luminal exposure to heparinase or alfa‐chymotrypsin enzymes suggesting that the flow sensor of the bradykinin receptor (BR) is associated to a carbohydrate residue and/or a protein segment of the receptor present in the extracellular face of the plasma membrane. By looking at the available molecular structure of the BR we have identified a segment of the N‐terminus that could be acting as the flow sensor by a very simple physical mechanism. On the other hand, by using carotid cultured endothelial cells we have found that flow decreases the expression of p‐SRC protein and does not change the p‐ERK expression.Conclusionsthe mechanism by which flow is sensed by endothelial cells is still on debate. However, one mechanism for sensing the flow could be located at the extracellular segment of the protein receptor. The N‐terminus segment of the BR could move depending on the flow velocity and, as a consequence, increasing or decreasing the availability of the BR to its ligand.Support or Funding InformationSupported by Conacyt 223350 to RET.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Endothelium‐dependent vasorelaxation and blood pressure are preserved in mice with chronic hyperendothelinemia
Authors: Grunewald Zachary Ian , Jurrissen Thomas , Ball James R. , Woodford Makenzie , Walsh Lauren , Ramirez Francisco , Brown Scott , Aroor Annayya , Paradis Pierre , Schiffrin Ernesto , Bender Shawn , Martinez‐Lemus Luis , Padilla Jaume 
Published: June 2021

Endothelin‐1 (ET‐1) is a potent vasoactive peptide implicated in the development of glucose intolerance, endothelial dysfunction, and hypertension. However, whether the detrimental metabolic and vascular effects caused by chronically elevated circulating ET‐1 (i.e., hyperendothelinemia) are exacerbated by obesity remains unknown. Accordingly, six‐week‐old female transgenic mice overexpressing human preproET‐1 selectively in the endothelium (eET‐ 1) and non‐transgenic (i.e., wild‐type) littermates were fed either chow or a Western diet (46% Kcal fat, 36% Kcal carbohydrate) to induce obesity for 21 weeks, creating four distinct groups (n=9–11/group): wild‐type chow‐fed, eET‐1 chow‐fed, wild‐type Western diet‐fed, eET‐1 Western diet‐fed. eET‐1 mice exhibited a 27‐fold (chow) and 18‐fold (Western diet) elevation in plasma ET‐1 concentration relative to wild‐type mice. Notably, despite such marked elevations in plasma ET‐1, blood pressure (systolic and diastolic) and aortic stiffness, assessed by pulse wave velocity, were unaltered in eET‐1 mice relative to wild‐type counterparts, regardless of diet. Similarly, independent of diet, ex vivo endothelium‐dependent relaxation (i.e., vasomotor responses to acetylcholine and insulin) in femoral and coronary arteries were not different between eET‐1 and wild‐type mice, and modestly enhanced in the aorta of eET‐1 mice. eET‐1 mice also exhibited suppressed phenylephrine‐induced aortic vasoconstriction relative to wild‐type mice, an effect that was amplified by Western diet‐feeding. Chow‐fed eET‐1 mice exhibited mild glucose intolerance and this genotype effect was not aggravated by diet‐induced obesity. Collectively, contrary to our hypothesis, we find that endothelial overexpression of ET‐1 does not lead to impaired endothelial function in lean or obese mice. The retention of a functional endothelial phenotype and suppression of alpha‐adrenergic vasoconstriction in this model of chronic hyperendothelinemia may contribute to the preservation of normal blood pressure. Follow‐up experiments are ongoing to delineate potential homeostatic compensatory adaptations that underlie this largely conserved cardiometabolic phenotype in the presence of chronic hyperendothelinemia.Support or Funding InformationNIH, SCANThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
All‐Extremity High‐Intensity Interval Training and Moderate‐Intensity Continuous Training Improve Aerobic Fitness and Cardiac Function in Type 2 Diabetes
Authors: Christou Demetra D. , Hwang Chueh‐Lung , Lim Jisok , Yoo Jeung‐Ki , Kim Han‐Kyul , Hwang Moon‐Hyon , Handberg Eileen M. , Petersen John W. , Holmer Brady J. , Lapierre Stephanie S. , Sakarya Yasemin 
Published: June 2021

High‐intensity interval training (HIIT) on the treadmill has been reported to be more effective in improving aerobic fitness and cardiac function compared with moderate‐intensity continuous training (MICT) in adults with cardiometabolic disorders. However, middle‐aged and older adults with type 2 diabetes (T2D) are often unable to tolerate weight‐bearing exercise which may hinder HIIT and MICT on the treadmill. Therefore, the purpose of this randomized clinical trial was twofold: 1) to test if non‐weight bearing all‐extremity HIIT and MICT are feasible in adults with T2D aged 50 to 79 yrs; and 2) to test whether HIIT is more effective in improving aerobic fitness and cardiac function than MICT. Fifty‐three sedentary adults with T2D (age: 63±1 yrs), free of cardiovascular disease, were randomized to HIIT (n=21), MICT (n=18) or non‐exercise control (CONT; n=14). HIIT (4×4‐min intervals at 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on an all‐extremity ergometer, 4 times/week for 8 weeks under supervision. Aerobic fitness was assessed by oxygen consumption during an incremental maximal exercise test. Left ventricular (LV) function was assessed during rest by two‐dimensional echocardiography including conventional and tissue Doppler. All measures were obtained at pre‐ and post‐intervention. Approximately 80% of participants randomized to all‐extremity HIIT and MICT completed the exercise intervention. Aerobic fitness improved by 11% in HIIT (22.4±1.2 vs. 24.9±1.4 ml/kg/min, pre‐ vs. post‐intervention; P<0.0001) and 7% in MICT (21.4±1.3 vs. 23.0±1.3 ml/kg/min; P=0.004 and P=0.4 for HIIT vs. MICT), whereas it did not change in CONT (21.4±1.5 vs. 21.3±1.2 ml/kg/min; P=0.9). Ejection fraction, a measure of LV systolic function, increased in both HIIT and MICT by ~2% (HIIT: 54.7±0.7 vs. 56.6±0.9%; P=0.007 and MICT: 54.6±1.4 vs. 56.4±1.2%; P=0.04), whereas it remained unchanged in CONT (56.0±1.2 vs. 54.9±1.1%; P=0.2). Diastolic function was not significantly affected by the intervention (P≥0.06). In conclusion, all‐extremity HIIT and MICT are feasible in middle‐aged and older adults with T2D and are equally effective in improving aerobic fitness and LV systolic function.Support or Funding InformationThis work was supported by the National Institutes of Health (NIA AG 050203).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Augmented myogenic constriction in the SHR pre‐glomerular renal arteries protects the kidneys from elevated blood pressure
Authors: Nademi Samera , Lu Chao , Carlisle Rachel E. , Dickhout Jeffrey G. 
Published: June 2021

BackgroundSpontaneously Hypertensive Rats (SHR) have chronically elevated blood pressures (BPs) at 30 weeks of age (systolic: 191.0 ± 1.0, diastolic: 128.8 ±0.9). However, despite this chronic malignant hypertension, SHR kidneys remain relatively free of pathology and do not display significant proteinuria, due to having an augmented myogenic constriction (MC) in their kidneys [1–2]. In contrast to the SHR, high‐salt fed Dahl Salt Sensitive (DSS) rats have lower BPs (systolic: 163.2 ± 1.4, diastolic: 119.4 ± 1.1), yet show extensive renal pathology, proteinuria, and blunted myogenic response (MR) in the pre‐glomerular vessels. We hypothesize that augmented MC in the SHR pre‐glomerular vessels is due to prostanoid synthesis, providing renal protection.Methods/ResultsTo investigate this hypothesis, we used the inhibitor of prostaglandin H2 synthesis, indomethacin, in the SHR and WKY pre‐glomerular arteries. We also utilized N omega‐nitro‐L‐arginine (LNNA) to examine the effect of nitric oxide blockade on MC, and nifedipine to determine the dependence of MR on L‐type calcium channels. Further, we used a second vascular bed, the mesenteric arcades, to assess the effects of these modulators on myogenic tone. The results showed an enhanced MR in the SHR pre‐glomerular vessels compared to the WKY. Indomethacin attenuated MC in both WKY and SHR renal arteries and nifedipine completely blocked this response in both WKY and SHR pre‐glomerular vessels. In mesenteric arteries, indomethacin decreased MR at high intraluminal pressures in the WKY, and lower pressures in the SHR. LNNA did not change MR in either WKY or SHR, while nifedipine inhibited MC in both WKY and SHR vessels.ConclusionsSHR pre‐glomerular arteries show an augmented MC compared to WKY vessels. Prostaglandin increases MC in both WKY and SHR renal arteries. In mesenteric arteries, prostaglandin increases MC at high intraluminal pressures in WKY, but lower pressures in the SHR. Nitric oxide does not affect MR in mesenteric arteries, but L‐type calcium channels play a key role in this response in both renal and mesenteric vessels.Support or Funding InformationThis work was supported by Canadian Institutes of Health Research grants to Dr. Jeffrey G. Dickhout (PJT148499).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Inhibition of the human colonic thiamine pyrophosphate (TPP) uptake process by the pro‐inflammatory cytokine, TNF‐α and IFN‐γ
Authors: Srinivasan Padmanabhan , Chu Brian D , Geltz Erica T , Thompson Morgan M , Said Hamid M 
Published: June 2021

Thiamin in its pyrophosphate form, i. e., thiamin pyrophosphate (TPP), is essential for normal cellular functions due to its involvement in energy metabolism, maintenance of normal cellular redox state, and mitochondrial structure/function. Humans and other mammals obtain thiamin through intestinal absorption, as they lack the ability to synthesize the vitamin de novo. The vitamin is obtained from both dietary and microbiota sources. A considerable amount of the vitamin provided by the later source exists in the form of TPP. We have previously shown the existence of a specific and high‐affinity carrier‐mediated uptake process for TPP in human colonocytes (Am J Physiol Gastrointest Liver Physiol. 2012; 303: G389–95) and determined the molecular identity of the system involved (product of the SLC44A4 gene) (J Biol Chem. 2014; 289: 4405–16). We have also cloned the promoter of the SLC44A4 gene and delineated certain aspects of its transcriptional and post‐transcrptional regulation (Am J Physiol Cell Physiol 308: C750–C757, 2015; Am J Physiol cell Physiol. 2017; ajpcell.00169.2017). Pro‐inflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐ γ) are involved in the pathogenesis of inflammatory bowel diseases and has been shown to affect transport physiology of a variety of substrates. The effect of prolonged‐exposure of colonic epithelial cells to TNF‐α and IFN‐ γ on uptake of TPP has not been examined and was investigated in this study. The results showed that exposing the human‐derived colonic epithelial NCM460 cells to clinically relevant concentration of TNF‐α (20 ng/ml for 48hr) and IFN‐ γ (30 ng/ml for 48 hrs) leads to a significant (p < 0.01) inhibition in carrier‐mediated TPP uptake. This was associated with a significant reduction in the level of the expression of SLC44A4 protein, mRNA and hetronuclear RNA (hnRNA) levels, as well as in a significant inhibition in the activity of the SLC44A4 promoter. We also observed a significant decrease in the expression of the transcription factor ELF3 (which drive the SLC44A4 promoter) following exposure to TNF‐α and IFN‐ γ. Studies are in progress to understand the exact molecular mechanism involved in this process. This study for the first time provide clear evidence that exposure of human‐derived colonic epithelial NCM460 cells to TNF‐ α and IFN‐ γ negatively affect the colonic TPP transport, and that the effect is mediated at the level of transcription of the SLC44A4 gene.Support or Funding InformationSupported by grants from the DVA and the NIH (DK‐56061, DK58057, and AA 018071)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 effects of starch‐entrapped microsphere supplementation on obesity and insulin resistance in C57BL/6J mice
Authors: McNabney Sean M , Reed Kylee M , Starrs Grace E , Libbey Margaret E , Henagan Tara M 
Published: June 2021

Dietary supplementation with the short chain fatty acid butyrate prevents obesity and insulin resistance in mice fed a high fat diet (HFD). Unfortunately, the translational potential of dietary butyrate supplementation is limited due to its teratogenic effects at higher doses. More recently, attention has turned to resistant starches that produce butyrate during their fermentation in the colon as therapeutic agents for attenuating obesity and insulin resistance. These starches represent an effective strategy to enhance endogenous butyrate production. The entrapment of resistant starch in an alginate matrix represents a novel technique to increase fermentable carbohydrate delivery to the colon. The purpose of this study was to assess the effects of starch‐entrapped microsphere (SM) supplementation on body composition, insulin sensitivity and energy expenditure in a murine model of diet‐induced obesity. Male C57BL/6J mice were fed the following diets (N=10/group): 1) low fat diet (LF, 10% kcal fat), 2) HFD (HF, 60% kcal fat), or 3) HFD + 10% wt/wt SM (HF+SM, 60% kcal fat). Body weight and 48 h food consumption were measured weekly. Body composition was assessed weekly using EchoMRI, with scans performed in duplicate. Glucose tolerance tests (N=5/group) were performed after 7 wks of feeding and area under the curve (AUC) was determined. Energy expenditure (N=5/group) was assessed via CLAMS at 9 wks of feeding. All data were analyzed via repeated or one‐way ANOVA and post hoc Tukey tests as appropriate. Body weight, percent fat mass and GTT AUC was significantly greater in HF compared to LF. Energy expenditure and respiratory exchange ratio (RER) were significantly decreased in HF compared to LF; whereas, caloric consumption was increased. Although HF+SM showed significantly increased body weight and percent fat mass relative to LF, both body weight and percent fat mass were significantly decreased compared to HF. There was no significant difference in GTT AUC between LF and HF+SM. HF+SM showed significantly decreased GTT AUC compared to HF. Energy expenditure in HF+SM was not different from LF and was significantly increased compared to HF. RER was significantly decreased in HF+SM compared to LF and not different between HF and HF+SM. Interestingly, food consumption was significantly increased in HF+SM compared to both LF and HF groups. Collectively, our data show that dietary SM supplementation attenuates HFDinduced obesity and insulin resistance through upregulation of whole body energy expenditure, despite increased caloric intake, and may be an effective treatment strategy for obesity and insulin resistance.Support or Funding InformationThis work was supported by a AgSeed grant to TMH.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 Aronia melanocarpa Extract on Lifespan and Stress Resistance in C. elegans
Authors: Brown Cyrus , Lopez Virgilio , Lee Elaine C 
Published: June 2021

Oxidative stress caused by exposure to reactive oxygen species (ROS) induces widespread damage within the cell. ROS have damaging effects on the structure of DNA, proteins, and lipids, which contributes to the pathology of numerous diseases such as Parkinson's, Alzheimer's, and cancer. Cellular stress response mechanisms serve to mitigate the effects of oxidative stress by using antioxidant compounds to neutralize ROS. Black chokeberry (Aronia melanocarpa) is considered to be an excellent source of antioxidants such as polyphenols, anthocyanins and pro‐anthocyanins. The aim of this study was to investigate whether a crude mixture of Aronia extract would increase lifespan and stress resistance in Caenorhabditis elegans. N2 Bristol strain survival and stress resistance were tested with toxicity (0 mg×mL−1, 0.1 mg×mL−1, 1 mg×mL−1, 5 mg×mL−1, and 10 mg×mL−1, A. melanocarpa) and heat stress assays. Supplementation with 0.1 mg×mL−1 Aronia significantly increased survival as compared to the control condition (p = 0.006). No significant difference in survival was observed with Aronia supplementation during heat stress (p = 0.27). In conclusion, these data suggested Aronia supplementation had a beneficial effect on worm survival. However, more research is necessary to determine its effect on survival and resistance in response to cellular heat stress.Support or Funding InformationNew investigator start‐up, McNair Scholar ProgramThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
REDD1 Reduces Muscle Metabolism to Foster Adaptation under Fasting
Authors: FAVIER Francois , Britto Florian , Belloum Yassine , Gallot Yann , Cortade Fabienne , Chabi Beatrice , Freyssenet Damien , Carnac Gilles , Rieusset Jennifer , Giorgetti‐Peraldi Sophie , Ollendorff Vincent 
Published: June 2021

Aims and backgroundRegulated in Development and DNA Damage 1 (REDD1) is a stress‐induced protein responsible for the inhibition of the Akt/mTORC1 pathway. This pathway integrates energetic status and oxygen availability to promote protein and glycogen synthesis as well as mitochondrial biogenesis. REDD1 is expressed in response to exercise, hypoxia or fasting and has been observed in the mitochondrial fraction in vitro. Our aim is to characterize the role of REDD1 in skeletal muscle under energetic challenge.Methods and resultsWild‐type (WT) and REDD1 knockout (KO) mice were deprived of food for 16h and immediately killed before gastrocnemius and tibialis anterior muscles sampling. We observed an overactivation of the metabolic sensor AMPK and a greater glycogen depletion in skeletal muscle of REDD1 KO mice after fasting. In addition, REDD1 deficient mice displayed exacerbation of skeletal muscle atrophy in response to food deprivation compared to WT animals. We then used dexamethasone treatment to induce REDD1 protein expression and showed for the first time that REDD1 is (partly) localized at the mitochondrial‐associated endoplasmic reticulum membranes (MAM) of skeletal muscle fibers, where it is able to inhibit the Akt/mTORC1 pathway. Indeed, REDD1 binds to and reduces the interaction of MAM protein components, resulting in decreased mitochondrial O2 consumption and protein synthesis.ConclusionsSustained activity of the Akt/mTORC1 pathway is known to promote anabolic processes and therefore to increase ATP consumption. Our results supports that REDD1 deletion contribute to maintain high fuel demand that in turn leads to skeletal muscle atrophy under fasting. We propose here that a physiological role for REDD1 is to foster skeletal muscle acclimatization during energetic challenges via reduction of O2 and ATP consumption assigned to synthesis processes.Support or Funding InformationThis work was supported by the Agence Française de Lutte contre le Dopage (grant #4299).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.