bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF‐kB dependent mechanisms of high fat mediated cardioprotection.
Authors: Haar Lauren , Ren Xiaoping , Bertaux‐Skeirik Nina , Tee Trisha , Tranter Michael , Jones WK 
Published: June 2021

Clinical and epidemiological studies show that increases in serum cholesterol decrease morbidity in patients following myocardial infarction (MI). Serum cholesterol increases as a result of dietary intake of fat and is known to increase risk for primary myocardial events and associated co‐morbidies such as diabetes, myocardial infarction, athlerosclerotic legions, and some cancers.The effects of acute high fat feeding were assessed with a murine model of myocardial ischemia reperfusion injury. Mice fed on a high fat diet for 24hrs – 2 wks prior to ischemia/reperfusion (30 min coronary ligation) exhibited a profound cardioprotection against resulting MI relative to mice fed on a control diet (~70% reduction of infarct size P ≤ 0.05). This cardioprotective effect is not apparent until 12–24 hrs after initial feeding and also remained for 24–48 hrs following cessation of feeding, indicating a delayed or prolonged phase of cardioprotection. NF‐κB‐dependent gene expression is a well‐established mediator of the late‐phase of preconditioning cardioprotection. Our results show abrogation of this high‐fat diet mediated cardioprotection in a mouse model with cardiac‐specific blockade of NF‐κB. We then assessed the effect of high fat diet on downstream NF‐κB‐dependent genes. Results suggest that expression of NF‐κB‐dependent genes in the myocardium is triggered by the high fat diet, perhaps by the effects of lipid loading, changes in myocardial fat composition, neurohormonal, and/or cytokine/chemokine responses. Studies will be directed towards understanding the mechanism of this activation.
Canonical correlation analysis identifies key diet macronutrients related with metabolic and cardiovascular disorders in rodents submitted to hypercaloric diet
Authors: Junior Silvio Assis Oliveira , Padovani CR , Silva NR , Martinez PF , Campos DHS , Okoshi MP , Okoshi K , Cicogna AC 
Published: June 2021

This study analyzed the correlation between diet macronutrients and cardiovascular parameters in rats subjected to hypercaloric diet (HD).MethodsWistar‐Kyoto rats (n=20) were fed a standard control (C; 3.2Kcal/g) or hypercaloric diet (HD; 4.6Kcal/g) for 20 weeks. Afterward, glycemia and insulin were evaluated in serum samples. Systolic blood pressure (SBP) was analyzed by tail pletismography. Echocardiography was used to analyze structure and performance of the heart. Morphometric analysis was assessed in myocardial histological sections. Myocardial myosin heavy chain (MyHC) isoforms were analyzed by electrophoresis.Statistical analysisStudent's t‐test and canonical correlation.ResultsHD reduced glycemic tolerance and induced cardiac hypertrophy combined with improved systolic performance; additionally, HD increased collagen interstitial fraction (C: 3.7±1.2; HD: 5.4±1.8%; p<0.05) and β/α‐MyHC ratio (C: 0.87±0.27; HD: 1.43±0.67; p<0.05). Saturated lipid intake significantly correlated with glycemia, and multiple myocardial parameters of structure and performance (r=0.99; p<0.05).ConclusionSaturated lipids intake is directly correlated with glycemic changes and cardiac remodeling in rodents submitted to HD.
Chronic Interval Exercise Modifies the Myocardial Lipid Profile in a Miniature Swine Model of Heart Failure with Preserved Ejection Fraction
Authors: Emter Craig Allen , Rector R. Scott , Baines Christopher P. , Ford Kaitlin D. , Ford David A. 
Published: June 2021

Manipulation of dietary lipid intake and exercise has demonstrated beneficial effects in preventing the progression of heart failure (HF). We have previously shown chronic exercise prevents mitochondrial dysfunction characterized by increased mitochondrial permeability transition. Recent studies examining impaired mitochondrial function have focused on cardiolipin, a mitochondria‐localized phospholipid that decreases during HF. Our purpose was to examine the effect of chronic exercise on myocardial lipid phenotype in aortic‐banded mini‐swine with compensated HF. Shotgun lipidomics was used to examine alterations in ventricular lipids in male control (n=7), sedentary HF (n=4), and exercise trained HF (HF‐TR, n=7) animals. Total cardiolipin was significantly increased in the HF‐TR animals. Specific modifications in the cardiolipin pool were found in the tetralinoleoyl cardiolipin molecular species. Differences in triacylglycerol and ceramide molecular species were also observed. In conclusion, our novel results demonstrate the efficacy of exercise in modulating myocardial lipid profile in a large animal model of HF. We propose that our previous observation of exercise‐dependent preservation of normal mitochondrial function may be mediated via modification of myocardial lipid phenotype.Research support: NIH HL074214, HL111906 (DAF), HL093982‐01, HL101332 (CAE), and VA‐CDA2 (RSR).
Garlic (Allium sativum) attenuate glomerular glycation in Streptozotocin‐induced diabetic rats
Authors: Al‐Qattan Khaled K , Thomson Martha , Ali Muslim , Mansour Mohamed H 
Published: June 2021

BackgroundIn diabetes, hyperglycemia causes microangiopathy while garlic is effective in keeping euglycemia.ObjectiveThis study investigated the effect of 8 week‐single daily i.p. garlic extract injection on glomerular glycation in Streptozotocin‐induced diabetic rats.MethodUrine volume and creatinine and serum insulin, glucose, creatinine and erythrocyte hemoglobin glycation (GHb) were measured at different times in diabetic‐control (D‐C), diabetic‐garlic (D‐G) treated and normal‐control (N‐C) rats. Images, glycation and count of normal and abnormal renal corpuscles (RC) were taken and estimated by light microscopy and Periodic Acid Shiff (PAS) staining.ResultsCompared to N‐C, D‐C showed significant decrease in serum insulin and increase in urine volume and creatinine and serum glucose, creatinine and GHb. D‐C also showed prevalent characteristic RC damage and intense diffused glomerular PAS activity. D‐G showed significant increase in serum insulin and decrease in urine volume and creatinine and serum glucose, creatinine, GHb. In D‐G significantly less damage of RC was obvious. In addition, PAS activity and distribution was close to that in N‐C.ConclusionGarlic is effective in inducing euglycemia ‐ one way by insulinemia ‐ thus attenuating glomerular glycation and preserving some renal clearance function.
Effect of Induced Hypothermia on Microvascular Inflammation During Hemorrhagic Shock/Resuscitation
Authors: Coyan Garrett N , Moncure Michael , Thomas James H , Holloway Naomi , Wood John G 
Published: June 2021

IntroductionMicrovascular inflammation caused by hemorrhagic shock is associated with increased morbidity and mortality in trauma patients. Hypothermia has been shown to be a novel approach in preventing morbidity and mortality in several clinical scenarios.ObjectiveOur goal was to determine if induced hypothermia during hemorrhagic shock/resuscitation attenuated leukocyte adherence and mast cell degranulation in the rat mesenteric microcirculation.MethodsIntravital microscopy was used to visualize the mesentery in real time. Ruthenium red was superfused over the mesentery throughout the experiment to assess mast cell degranulation. After a control period, blood pressure was reduced to 40–45 mm Hg for 1 hour by withdrawal of blood. During 2 hours of resuscitation, temperature was reduced to 32–34°C. The animal was then re‐warmed for 2 hours to 37–38°C.ResultsLeukocyte adherence and mast cell degranulation were decreased during hypothermic resuscitation compared to normothermic resuscitation. However, both leukocyte adherence and mast cell degranulation increased during the re‐warming period in comparison to the hypothermic period.ConclusionWe have shown that induced hypothermia during resuscitation attenuates microvascular inflammation, but this response may only be temporary as shown by an increase in leukocyte adherence during the re‐warming period.
Caloric restriction and resveratrol attenuate doxorubicin‐induced vascular dysfunction in old rat mesenteric arteries
Authors: Whidden Melissa Ann , Kirichenko Nataliya , Dutta Debapriya , Xu Jinze , Leeuwenburgh Christiaan , Tumer Nihal 
Published: June 2021

Doxorubicin (DOX) is associated with oxidant‐induced damage to the endothelium and vascular dysfunction. Both caloric restriction (CR) and resveratrol (Res) have been shown to lower levels of oxidative stress and slow aging. So, we examined CR and Res alone and in combination on DOX‐induced vascular dysfunction in old mesenteric arteries (MA). 26 month male F‐344xBN rats were divided into: ad libitum (AL), AL+DOX, 20% CR, CR+DOX, Res, Res+DOX, CR+Res, and CR+Res+DOX. Over 6 wks rats consumed a 20% CR diet while Res (5 mg/kg/day) was given in pellets. DOX (10 mg/kg BW) was administered 24 hrs prior to sacrifice. Concentration‐response curves to Ach (10–9–10–5 M) with and without L‐NAME were evaluated in pressurized MAs. Endothelium‐mediated relaxation was significantly reduced in DOX (38 ± 4%) when compared with AL (76 ± 2%) rats (P<0.001). Alone, both 20% CR and Res attenuated the DOX‐induced reduction in dilation; 20% CR (56 ± 3%, P<0.05) and Res (70 ± 4%, P<0.01). There was no additive protection from DOX when treatments were used together. L‐NAME decreased responses to Ach in AL and treatment arteries and inhibited the reduced responses in the DOX MAs. These findings demonstrate that both antioxidant treatments contribute to the attenuation of vascular dysfunction found with DOX, however, Res appears to be more protective to the vascular system.Supported by NIH AG17994, 1P30AG02874, Department of Veteran Affairs.
Smooth muscle microRNAs regulate serotonin‐induced contraction in pulmonary and systemic arteries
Authors: Dahan Diana , Hellstrand Per , Swärd Karl , Albinsson Sebastian 
Published: June 2021

MicroRNA (miRNA) are short, non coding RNA that regulate mRNA expression levels and/or translational efficiency. MiRNAs are important for vascular smooth muscle development and function by regulating phenotypic modulation and contractile responses. Contractility of vascular smooth muscle is essential for regulation of blood pressure and blood flow. A number of contractile agonists can affect vascular reactivity and altered sensitivity to these agonists may play a role in vascular disease.The aim of this study was to identify the role of miRNAs in vascular responses to various contractile agonists.Vascular reactivity was assessed in isolated pulmonary arteries and aortic rings from tamoxifen‐inducible and smooth muscle specific Dicer KO mice 5 weeks post tamoxifen and in constitutive miR‐143/145 KO mice.Our results show a specific increase in the contractile response to serotonin in the pulmonary artery and aorta. This effect was not found in miR‐143/145 KO mice and is therefore likely to be dependent on other smooth muscle miRNAs. The increased contractile response to serotonin in Dicer KO vessels was reduced by Src‐inhibitors but less sensitive to Rho‐kinase inhibition.The precise mechanisms for augmented serotonin‐induced contraction in Dicer KO vessels are now under investigation and may identify a novel role for specific miRNAs in vascular disease.
Americans with Diabetes are Adhering to a Low Glycemic Diet but are Eating a High Fat Southern Diet which is Associated with Cardiovascular Disease
Authors: Pearson Keith , Shikany James , Fernandez Jose , Judd Suzanne 
Published: June 2021

Traditional diabetes nutrition education has emphasized consuming a high fiber, low glycemic diet. Healthy diet adherence has previously been analyzed by examining individual foods and nutrients; however, focusing on overall dietary patterns may be more practical for disease monitoring. Through factor analysis on 56 food groups (obtained from the Block98 Food Frequency Questionnaire), using a nationally representative sample of 21,636 black and white participants in the REGARDS study (age >; 45), five dietary patterns emerged. Logistic regression was used to calculate odds ratios (OR) for adherence to each dietary pattern. People with diabetes were more likely (OR=1.18, p<0.001) to adhere to a plant based dietary pattern, less likely to adhere to a high sweets pattern (OR=0.77, p<0.001) and more likely to adhere to a Southern style pattern (OR=1.27, p<0.001) after adjustment for age, race, sex, education and income. Our results suggest that even if people with diabetes are adhering to low glycemic recommendations, they are still consuming fried foods and added fats typical of a Southern dietary pattern. Given our previous work showing a twofold increased risk of cardiovascular disease (CVD) with a Southern diet – and since diabetes is a risk equivalent for CVD ‐‐ future education may need to stress a reduction in Southern dietary patterns to improve cardiovascular health.Grant Funding Source: NIH‐NINDS and a grant from General Mills
Effects of high‐fat diet on metabolic parameters and exercise performance of young and adult rats
Authors: Li Zhen‐Jie , Chen Chiao‐Nan 
Published: June 2021

Background and purposeHigh fat diet (HFD) decreases mitochondrial function and impairs metabolic characteristics in animals. Interestingly, it has been shown that the very young animals are more resistant to the HFD‐induced mitochondria impairment than young animals. Since the function of mitochondria and the metabolic characteristics are associated with the exercise performance of animals, it is interesting to know whether the negative influence of HFD on exercise performance and metabolic characteristics is less in young animals compared to adult animals.MethodYoung (4‐month‐old) and adult (9‐month‐old) rats were randomized into regular chow diet (control) and HFD groups and received respective diet intervention for 14 weeks. Body weight (BW), systolic blood pressure (SBP) and exercise performance including grip test, Rota‐rod test, and treadmill running test were determined at baseline, after 7 weeks and after 14 weeks of intervention.ResultRats, both young and adult, fed with HFD showed greater increase of BW and SBP and less increase of normalized grip strength than control groups after 7 weeks and 14 weeks of diet intervention. Treadmill running time was found significant decreased in both young and adult rats on HFD for 14 weeks.ConclusionHFD has negative effects on BW, SBP and exercise performance not only in adult but also in young animals.
Combined aminophylline and ambrisentan is a potentially safe treatment of health complications after rapid ascent to high altitudes
Authors: Schroeder Thies , Irwin David , Hamilton Karyn , Boico Alina , Blueschke Gert 
Published: June 2021

Combined theophylline and ambrisentan improve exercise tolerance in rats after rapid ascent to high altitude, by accelerating blood flow and oxygen delivery to peripheral tissues. We hypothesized that this combination is also safe in humans, and that the single drugs do not interact.MethodsHealthy human subjects were randomized to one of two sequences. Sequence A was a single 400 mg dose of aminophylline (soluble form of theophylline) followed by 48 h washout, then 5 mg of ambrisentan followed by 48h washout, then 400mg aminophylline and 5mg ambrisentan combined. Sequence B was the same, except subjects were dosed first with ambrisentan and then aminophylline. Adverse event (AE) and pharmacokinetic (PK) profiles were assessed.ResultsOf 47 subjects recruited, 18 completed all procedures. Total 70 transient AEs of mild (71%), moderate (26%) or severe (3%) intensity occurred, most in the first cohort of subjects [64 (91%)] and following aminophylline given alone (38%) or combined with ambrisentan (47%). As expected, PK curves showed no drug interaction.ConclusionsCombined dosing with the xanthine aminophylline and the endothelin receptor antagonist ambrisentan is safe in healthy humans, and these drugs do not interact. AE profiles were as expected and mostly due to the high dose of aminophylline. An upcoming trial will test this drug combination for safety and efficacy in hypoxic exercising human subjects.
Phosphorylation of rat skeletal muscle pyruvate dehydrogenase phosphatase in response to insulin stimulation
Authors: Choptiany Jonathan , MacPherson Rebecca , LeBlanc Paul , Peters Sandra 
Published: June 2021

Pyruvate dehydrogenase phosphatase (PDP) regulates carbohydrate oxidation through the mitochondrial pyruvate dehydrogenase (PDH) complex. PDP dephosphorylates and activates PDH, enabling increased carbohydrate flux towards oxidative energy production. In cell culture, both PDP1 and 2 appear to undergo covalent activation in direct response to insulin–stimulation by PKCδ. Our objective was to examine the effect of insulin on PDP phosphorylation and PDH activation. Intact rat extensor digitorum longus muscles were incubated (oxygenated at 25°C, fixed to 1g of resting tension) tendon–to–tendon for 30min in basal or insulin–stimulated (10mU/mL) media. PDH activity increased 58% following insulin stimulation, (p=0.057, n=11). Serine phosphorylation of PDP1 (p=0.037) and PDP2 (p=0.027) increased by 44% and 54% respectively following stimulation (n=4), and PKCδ protein content was enriched in the mitochondrial fraction by 45% in response to insulin stimulation (p=0.0009, n=8). These data suggest that the insulin–stimulated increase in PDH activity in whole tissue is mediated through mitochondrial migration of PKCδ and subsequent PDP phosphorylation.Research supported by NSERC, Canada.
Overexpression of Bnip3 in the Myocardium Leads to Mitochondrial Dysfunction and Enhanced Mitochondrial Autophagy
Authors: Lee Youngil , Thomas Robert L , Kubli Dieter A , Zhang Xiaoxue , Dorn Gerald W , Gustafsson Åsa B 
Published: June 2021

A pro‐apoptotic BH3‐only protein Bnip3 in cells leads to mitochondrial dysfunction and cell death, and induction of mitochondrial autophagy. To date, most studies on Bnip3 have been performed in vitro. Using cardiac specific Bnip3 transgenic (Tg), we have investigated the consequences of Bnip3 overexpression in the heart. We found that mitochondrial respiratory function was significantly impaired in 10 weeks old Bnip3 Tg hearts compared to WT. Moreover, number of mitochondria (decreased mtDNA copy number) and yield of isolated mitochondria were significantly reduced compared to WT. Bnip3 overexpression also caused increased induction of autophagy in the heart. We also found increased mitochondrial translocation of the fission protein Drp‐1 and the E3 ubiquitin ligase Parkin which correlated with increased ubiquitination of mitochondrial proteins, and that PINK1 and histone deacetylase 6 (HDAC6), known markers of mitochondrial autophagy, were increased in the heart of Bnip3 Tg mice. Interestingly, echocardiography revealed that Bnip3 Tg cardiac function was not significantly different from WT mice. Taken together, these data suggest that Bnip3‐mediated mitochondrial damage and increased clearance do not lead to heart failure, indicating that the damage does not exceed the mitochondrial reserve capacity in the heart under non‐stressed conditions.Supported by NIH R01 HL087023
A school feeding program based on the Eco‐Health approach: A case study from rural Lebanon
Authors: Batal Malek , Ghattas Hala , Abou‐Ezze Rheam 
Published: June 2021

Using the Eco‐Health approach, a local women's cooperative was paired with a rural school to provide traditional foods to children through a school feeding and nutrition education program. We investigated the effect of this program versus nutrition education alone on nutritional status, breakfast consumption and attitude towards traditional diets. Two elementary schools from the village of Aarsal, Lebanon participated in the study. At baseline and endpoint, height, weight, hemoglobin and breakfast recall were taken. All children received four nutrition education sessions and children from the intervention school received a daily school meal for 4 days/week for 5 months. Qualitative data were collected from meetings with parents. At baseline, stunting, overweight and anemia prevalence were at 8%, 20% and 6%, respectively. There was a significant decrease in anemia prevalence among schoolchildren taking part in the school feeding intervention (p<0.0001). Breakfast consumption habits improved at both schools with a significant decrease in number of children not consuming breakfast (p<0.001). Schoolchildren in the intervention school demonstrated improved attitudes towards traditional diet and healthy lifestyle practices. This school feeding program provides a potentially sustainable local model for school feeding programs in similar rural contexts in countries undergoing a nutrition transition.This research has been funded by Canada's International Development Research Center (IDRC).
Liver X Receptor activation inhibits intestinal phosphate transport
Authors: Jelen Sabina , Giral Hector , Caldas Yupanqui , Sutherland Eileen , Levi Moshe 
Published: June 2021

Renal Pi reabsorption has been considered the main mechanism controlling Pi homeostasis. However, recently small intestine Pi absorption has emerged as a putative pharmacological target for the control of hyperphosphatemia, especially important in the setting of chronic kidney disease. We have recently reported that activation of Liver X Receptor (LXR) with LXR agonists leads to a decreased serum Pi concentration and increased urinary Pi excretion. In parallel, these changes were associated with the decrease of renal and intestinal NaPi transporters expression. To investigate the potential mechanisms behind this regulation we used two transgenic mouse models expressing: 1) constitutively active form of the LXRα fused with the activation domain of VP16 under LXRα endogenous promoter (VP16‐LXRα Tg); 2) enterocyte‐specific LXRα under villin promoter (villin VP16‐LXRα Tg).VP16‐LXRα Tg and villin VP16‐LXRα Tg mice showed reduced sodium dependent Pi uptake in the brush border membrane (BBM) of enterocytes. This was accompanied by reduction of NaPi2b protein abundance in the BBM and also reduced ileum NaPi‐2b mRNA level.Our results show that the effects of enterocyte‐specific activation of LXR are independent of systemic influences and also highlight importance of the intestine in Pi homeostasis regulation. However, the putative mechanisms of LXR effects on Pi transport remain to be elucidatedSupported by NIH
CelluCCCClar changes in human tendon cells as a result to release of mechanical tension
Authors: Bayer Monika Lucia , Schjerling Peter , Heinemeier Katja Maria , Gullberg Donald , Herchenhan Andreas , Krogsgaard Michael , Kjaer Michael 
Published: June 2021

The objective was to study the effect of tension release on human tendon cell gene expression and cell‐matrix interaction. Tendon cells in healthy tendon are subjected to tensile load, but in injured tendon, this stimulus is disrupted. This might lead to substantial cellular changes and alterations in cell‐matrix interactions, thereby complicating healing. Differentiated tendon cells express scleraxis, tenomodulin (Tnm), Mohawk homeobox (Mkx) and several matrix proteins, and tendon cells bind to the matrix through integrins. We hypothesized that tension release will lead to a downregulation of tendon‐specific genes and a decline of proteins by which cells interact with the matrix. Tendon‐like tissue was engineered with human tendon cells and cultured under static load or in the absence of load. Samples were collected 6 days post tension release and analyzed for gene and protein expression. Release of tension reduced gene expression of Tnm, Mkx, collagen type I, III, XII and XIV and decorin (p< 0.05) and preliminary results show decreased protein levels of the collagen receptor integrin α11. The study emphasizes the importance of tensile load on cell differentiation and formation of cell‐matrix contacts. The de‐coupling of cell‐matrix interactions might be a crucial factor in tissue injury and regeneration.Research was supported by the Danish Medical Research Council, the Nordea Foundation and Lundbeck foundation.