bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time Course of Blueberry Ingestion on Measures of Arterial Stiffness and Blood Pressure
Authors: McAnulty Lisa , Pike Julieanne , Collier Scott R. , Thompson Kyle L. , McAnulty Steven R. 
Published: June 2021

IntroductionAn individual's risk of cardiovascular disease is affected by numerous factors, with hypertension among the most significant. Specifically, hypertension causes increased pressure within the blood vessels which can compromise the integrity of the vasculature. Blueberries possess compounds known as anthocyanins which exert anti‐hypertensive properties and may reduce blood pressure. The objective of the present study was to examine the effect of daily blueberry ingestion on blood pressure, augmentation index (AIx), and central pulse wave velocity (cPWV) over a three week period, as well as to assess acute effects, one hour and two hours post‐consumption.MethodsParticipants (n=22) were composed of men and women between the ages of 40 to 70 years who met pre‐determined inclusion criteria. Participants were randomized into group A (n=10) or B (n=12) and received 38 g/d of freeze‐dried blueberry powder or placebo, respectively. Participants had baseline values obtained and then consumed A or B every evening with dinner for three weeks. Blood pressure, AIx, and cPWV were measured at the end of each week. At the end of the third week, participants had the weekly measures taken and then ingested 38g of A or B and had acute measures taken at one hour and two hours post ingestion.ResultsParticipants did not differ based on age, height, weight, body mass index, or percent body fat. Chronic blueberry ingestion resulted in significant treatment time interaction effects for systolic blood pressure (p=0.036). No chronic treatment time interactions were observed for diastolic blood pressure, AIx, or cPWV. With respect to one hour and two hours post‐consumption, significant treatment time interaction effects were found for systolic blood pressure (p=0.015). No acute treatment time interactions were found for diastolic blood pressure, AIx, or cPWV. Furthermore, no significant treatment time interactions were observed for energy, macronutrient, or micronutrient intake including nutrients known to affect blood pressure.ConclusionOf interest was the change in systolic blood pressure following both acute and chronic dosing. It was not supported to be mediated by a change in vessel distensibility since PWV was not altered. Therefore, the change in blood pressure was most likely due to a change in HR both following acute supplement ingestion and as a chronic effect over time. This finding is of interest due to the relatively short time course and requires further investigation.Support or Funding InformationU.S. Highbush Blueberry CouncilThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Microvascular Endothelial Dysfunction is Evident in Adults with Stage 1 Hypertension as Defined by the 2017 ACC/AHA Guidelines
Authors: Shank Sean , Greaney Jody , Alexander Lacy 
Published: June 2021

The American Heart Association and American Council of Cardiology recently updated the guidelines defining hypertension to systolic blood pressure (BP) values >130 mmHg or diastolic BP values >80 mmHg (i.e., Stage 1 hypertension; HTN1). Hypertensive adults classified via the 2003 JNC7 definition (systolic BP >140 mmHg or diastolic BP >90 mmHg) are now categorized as having Stage 2 hypertension (HTN2). Adults with HTN2 exhibit pronounced microvascular dysfunction, one of the first pathophysiological manifestations of the disease. However, the degree to which endothelial dysfunction is evident in the microcirculation of adults meeting the updated definition of hypertension (HTN1) remains equivocal. We tested the hypotheses that microvascular endothelial dysfunction would be present in HTN1 compared to normotensive adults (NTN; systolic BP <120 mmHg and diastolic BP <80 mmHg) but would be less severe compared to HTN2. Endothelium‐dependent dilation (EDD) was retrospectively analyzed in 21 NTN (5 M; 51±1 yrs; resting BP 107±1/68±1 mmHg), 15 HTN1 (6 M; 54±1 yrs; resting BP 126±1/82±1 mmHg), and 37 HTN2 (24 M; 54±2 yrs; resting BP 144±1/93±1 mmHg). Red blood cell flux (laser Doppler flowmetry) was measured during graded intradermal microdialysis perfusion of the endothelium‐dependent agonist acetylcholine (ACh; 10−10–10−1 M). EDD was assessed as flux (perfusion units; PU) and cutaneous vascular conductance (CVC; flux·mmHg−1). Systolic and diastolic BP were significantly different between all three groups (P<0.05 for all). EDD was blunted in both HTN1 and HTN2 relative to NTN when expressed as both flux (NTN: 74±2 vs. HTN1: 60±3 vs. HTN2: 59±2 PU; all P<0.01) and CVC (NTN: 0.86±0.03 vs. HTN1: 0.62±0.04 vs. HTN2: 0.58±0.02 flux·mmHg−1; all P <0.01); however, ACh‐induced dilation was not different between HTN1 and HTN2 (flux P=0.9; CVC P=0.5). These preliminary data suggest that cutaneous microvascular endothelial dysfunction is evident in HTN1 and is as severe relative to HTN2. Future studies are required in order to elucidate the mechanistic mediators of vascular regulation in HTN1.Support or Funding InformationFunding: NHLBI 5R01HL093238‐08, NIA 5T32AG049676‐02This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Urine connectin/titin is increased in patients after heart surgery with cardiopulmonary bypass
Authors: Tanihata Jun , Nishioka Naritomo , Inoue Takahiro , Bando Ko , Minamisawa Susumu 
Published: June 2021

Background and ObjectiveCardiac surgery with cardiopulmonary bypass (CPB) may accidentally cause perioperative cardiac injury, which would increase in the risk of substantial post‐operative morbidity and mortality. Therefore, the accurate evaluation of cardiac injury is important for patient care after surgery. Although several biomarkers from patients' serum have been already clinically available to detect cardiac injury, a sensitive urine biomarker for cardiac injury has not yet been established. Recently, N‐terminal fragment of connectin/titin (N‐connectin), a giant sarcomeric protein, has been reported to detect muscle damages in patients with skeletal muscle dystrophy and healthy volunteer with endurance exercise. In the present study, we tested whether urine N‐connectin can be a novel biomarker to detect cardiac damage after cardiac surgery with CPB.Methods and ResultsWe measured urinary levels of N‐connectin/creatinine (N‐connectin/Cr; pmol/mg/dl) in 13 patients (9 male, 4 female; 63±16 years old) who had undergone cardiac surgery with CPB have given informed consent to participate. The patients included 5 on‐pump coronary artery bypass graft surgery and 8 open‐heart surgery for various heart diseases. Urine N‐connectin/Cr before operation was 3.8 ± 2.8 pmol/mg/dL and it was significantly increased in all patients after surgery (42.8. ±16.4 pmol/mg/dL at the operation day). Serum creatine phosphokinase‐MB isozyme (CK‐MB) before operation was 7.6 ± 2.7 U/L and it was also significantly increased after surgery (48.0. ± 37.4 U/L at the operation day). Although serum CK‐MB was rapidly decreased to the pre‐operative level 3 days after operation, urine N‐connectin/Cr was still significantly high 3 days after operation (29.5 ±10.4 pmol/mg/dL). There was no difference in Urine N‐connectin/Cr between patients who underwent on‐pump coronary artery bypass graft surgery and open‐heart surgery. Urine N‐connectin/Cr at the operation day had no correlation with other parameters including serum CK‐MB, cardiopulmonary bypass time, duration of Intensive care stay, and post‐operative left ventricular ejection fraction.ConclusionUrinary N‐connectin/Cr was significantly increased after CPB and maintained high values at least 3 days after surgery. Urinary N‐connectin/Cr may be useful to detect the risk of substantial post‐operative cardiac damage.Support or Funding InformationThis work was supported by grants from The the Jikei University research found.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Hypertension Induces an Exaggerated Immune Response by Increasing CD86 Expression on Antigen Presenting Cells
Authors: Zhao Tuantuan , Li Yu , Bernstein Kenneth E. , Shen Xiao(Gregory) Z. 
Published: June 2021

Hypertension is a major cause of cardiovascular morbidity and mortality. Evidence indicates that inflammation is a key participant in the pathology of hypertension. However, how an elevation of blood pressure affects the immune response is still poorly understood. To study this, we immunized angiotensin II (Ang II) dependent hypertensive mice and normotensive mice with ovalbumin (OVA) and several different adjuvants. Elevated CD8+ and CD4+T cell responses specific to OVA were observed in hypertensive mice. To determine whether the exaggerated T cell responses in hypertension translate into increased tissue pathology, we studied two models of autoimmune disease. RIP‐mOVA is a transgenic mouse line that expresses membrane‐bound OVA in pancreatic islet β cells. Some of these mice were made hypertensive with either Ang II or L‐NAME. When OVA‐specific OT‐I T cells were infused into RIP‐mOVA mice, the hypertensive mice had significantly more OT‐I T cells infiltration into the pancreas, and they developed diabetes more rapidly, than normotensive RIP‐mOVA animals. Also, concanavalin A induced hepatitis was significantly worsened by hypertension as compared to the pathology observed in normotensive mice.The immune response above is due to the interaction of antigen presenting cells (APCs) and T cells. To study which cells are responsible for the heightened immune reactivity in hypertension, we characterized both T cells and APCs. We find that more effective APC presentation of antigen, and not differences in intrinsic T cell signaling, is a major instigator of the increased T cell response. For instance, OT‐I T cells from hypertensive mice responded similarly to such cells from normotensive mice when presented with OVA epitopes by normotensive APCs. In contrast, hypertensive APCs outperformed normotensive APCs in stimulating OT‐I T cells. Adoptive transfer of dendritic cells showed that APCs from hypertensive mice are responsible for the enhanced T cell response. We found that the key difference in the immune system of hypertensive mice is blood pressure mediated up‐regulation of CD86 on APCs. This is mediated by increased plasma ATP levels. These studies are the first to document that high blood pressure itself induces biochemical and immune changes that intensify inflammation in hypertension. They indicate ATP and CD86 as loci to potentially control hypertension associated inflammation.Support or Funding InformationNational Natural Science Foundation of China 31270950 (to XZS) NIH grant R21 AI114965(to KEB) NIH grant PO1 HL129941 (to KEB)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Assay of Insulin‐Stimulated Signaling by Flow Cytometry: Key Points of Regulation
Authors: Melendy Shawn , Hetrick Byron , McCurdy Carrie 
Published: June 2021

Type 2 Diabetes is an increasingly prevalent disease worldwide that is partially caused by a progressive loss of insulin response in adipose tissue and skeletal muscle, two essential insulin target tissues. Multicolor flow cytometry is a powerful tool that can be used to measure multiple signaling events simultaneously in specific cell types within mixed populations. The objective of this study is to design a sensitive and high‐throughput assay to measure key points of regulation in the insulin signaling pathway for adipocytes and myocytes using flow cytometry. We have developed a multicolor flow cytometry panel to measure the insulin stimulated phosphorylation of Akt (S473) and the transport of the insulin responsive glucose transporter GLUT4 to the plasma membrane. This assay is compatible with cell identity markers, such as CD56, to specifically measure insulin response of muscle cells within mixed populations. C2C12 myoblasts were stained with primary conjugated antibodies for pAkt (S473) and an extracellular region of GLUT4, indicating that GLUT4 is present in the plasma membrane. Both C2C12 myoblasts and non‐human primate primary myoblasts responded to insulin with increased pAkt (S473) and plasma membrane GLUT4 with an EC50 of <10nM, similar to physiological response. Akt phosphorylation and GLUT4 translocation were blocked by the actin depolymerizing agent Cytochalasin D. Future work will expand the panel to measure phosphorylation of insulin receptor substrate (IRS1) and phosphoinosital 3‐kinase (PI3K) activity by determining phosphoinosital (3,4,5) phosphate (PIP3) production. The sensitivity of the assay will be demonstrated with inhibitors to specific signaling events such as inhibition of PI3K by Wortmannin, and inhibition of Akt activation by MK‐2206. We anticipate that this will provide a powerful method to dissect the insulin signaling cascade in mixed populations of cells or to understand the role of specific regulatory elements in difficult to transfect primary cells.Support or Funding InformationSupported by an APS STRIDE Summer Fellowship (SM), the University of Oregon UROP Mini‐Grant (SM), and the National Institute of Diabetes Digestive and Kidney Diseases under Award R01 DK095926 (CEM).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Db/db Obese Mice Exhibit Enhanced Phosphorylation of p38, ERK1/2 and AKT in the Kidney
Authors: Haque Mohammed Ziaul , Kumar Vinod , Bettahi Ilham , Palaniyandi Suresh S. , Young Monika S. , Mohammad Ramzi M. , Abou Samra Abdul B. 
Published: June 2021

Altered metabolic states due to obesity and diabetes have a direct impact on renal structure and function. Obesity and diabetes leads to several key morphological, subcellular fibrotic remodeling, nephropathy and renal failure. However the clear signaling mechanism is not known. Leptin receptor deficiency is associated with obesity and hypercholesterolemia. We showed that acute cholesterol depletion increased cellular function and phosphorylation of p38, ERK and AKT kinases. Hence we hypothesized that obesity enhances phosphorylation of p38, ERK1/2 and AKT kinases in the kidney. To test our hypothesis we used kidneys from 25 weeks old four leptin receptor deficient db/db obese mice and their age matched four c57BL6 (wild type) mice. Transverse slices were made from similar position of all kidneys. Kidney slices were chopped into very small pieces and homogenized under the ice cold lysis buffer with protease and phospahtase inhibitors. The low spin pellets were discarded and the supernatants were collected. Kidney lysates were run through 7–12% poly acrylamide gel electrophoresis. Phosphorylations of p38, ERK1/2 and AKT were measured using western blot and cell signaling antibodies. The results were normalized to β‐actin as a control for protein loading using NIH image J software. Data of phospho proteins expressed in arbitrary units for p38 (14477 ±1703 vs. 22488±2773, p<0.03), ERK1/2 (12408 ±1965 vs. 21807±1467, p<0.01) and AKTThr308 (10173 ±462 vs. 18250±1198, p<0.01) were more in obese db/db mice compared to wild type mice. Total p38, ERK1/2 and AKT were not different between db/db and wild type mice. We conclude that obesity is associated with enhanced phosphorylation of p38, ERK and AKTThr308 which could be associated with altered renal structure and function.Support or Funding InformationHamad Medical Research Center #16304This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Augmented Skeletal Muscle Vasodilation to Intravascular ATP During Exercise and Systemic Hypoxia in Humans
Authors: Terwoord Janée D. , Racine Matthew L. , Hearon Christopher M. , Richards Jennifer C. , Luckasen Gary J. , Joyner Michael J. , Dinenno Frank A. 
Published: June 2021

We have recently demonstrated that vasodilation to the endothelium‐dependent agonist acetylcholine is amplified in contracting compared with quiescent skeletal muscle, highlighting the importance of the vascular endothelium in integrating vasomotor signals to regulate vascular tone in humans. In the present study, we tested the hypothesis that sensitivity to the endothelium‐dependent vasodilator ATP is augmented during exercise and systemic hypoxia, whereas sensitivity to the nitric oxide donor and endothelium‐independent dilator sodium nitroprusside (SNP) is not affected by these physiological conditions. In 12 young adults (7 M, 5 F), we measured forearm blood flow (FBF; Doppler ultrasound) and calculated changes in vascular conductance (FVC: quotient of FBF and mean arterial pressure) in response to local, intra‐arterial infusion of ATP or SNP during 1) control resting conditions (CON), 2) dynamic handgrip exercise (EX, 20 contractions per minute at 10% of maximal voluntary contraction), or 3) systemic hypoxia (HYP, 80% O2 saturation). Three doses of each vasodilator were infused via a brachial artery catheter during each condition (ATP: 1.25, 2.50, and 5.00 μg·dl forearm volume−1·min−1; SNP: 0.25, 0.50, and 1.00 μg·dl forearm volume−1·min−1). The order of drugs and conditions was randomized. Within each trial, infusions began after 3 min of rest, steady‐state exercise, or hypoxia, and each dose was infused for 2 min while the exercise or hypoxic stimulus was sustained. Compared to control conditions, vasodilatory sensitivity to the high dose of ATP was enhanced by 53 ± 18% during mild handgrip exercise (Δ FVC, CON: 120 ± 16 vs. EX: 176 ± 28 ml·min−1·100 mmHg−1; P < 0.05), whereas vasodilatory sensitivity was not affected at lower doses of ATP (P = NS; Dose × Condition interaction P < 0.05). In contrast, exercise had no effect on vascular sensitivity to any dose of SNP (P = NS). Similarly, during systemic hypoxia, vasodilation to ATP was enhanced by 18 ± 10% at the medium dose (Δ FVC, CON: 100 ± 15 vs. HYP: 125 ± 24 ml·min−1·100 mmHg−1; P < 0.05) and 28 ± 11% at the high dose (Δ FVC, CON: 120 ± 16 vs. HYP: 158 ± 27 ml·min−1·100 mmHg−1; P < 0.05; Dose × Condition interaction P < 0.05), whereas vasodilation to SNP was not different from control conditions at any dose (P = NS). These findings provide evidence that muscle contractions and hypoxia augment ATP‐mediated, endothelium‐dependent vasodilation in human skeletal muscle. Moreover, given that intravascular ATP increases under these physiological conditions, the results indicate that small changes in plasma ATP may result in augmented vasodilation and contribute to blood flow and oxygen delivery in humans.Support or Funding InformationHL119337This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Differences in Autonomic Recovery Following Maximal Resistance Exercise in Young and Older Adults
Authors: Schroeder Elizabeth C. , Rosenberg Alexander J. , Grigoriadis Georgios , Wee Sang Ouk , Fernhall Bo , Baynard Tracy 
Published: June 2021

Aging is associated with negative changes in autonomic function and an increased risk of cardiovascular disease. The risk of a sudden cardiovascular event is elevated during and immediately following vigorous exercise, potentially due to increased sympathetic dominance. Because resistance exercise provides a large hypertensive stimulus and young adults show reduced cardiac vagal control during recovery, further exploration of the effects of an acute bout of resistance exercise on autonomic function and recovery in older adults is required.PurposeTo evaluate the effects of high‐intensity lower body resistance exercise on autonomic modulation in young (YA) and older adults (OA).MethodsThirty‐five YA (17 female, 26±5 years, BMI: 23.8±3.2 kg/m2) and 25 OA (14 female, 60±6 years, BMI: 29.9±5.4 kg/m2) completed 3 sets of 10 repetitions of maximal isokinetic knee flexion/extension on a force dynamometer in a semi‐recumbent position. Throughout the protocol, participants were instrumented with a 3‐lead ECG and finger‐photoplethysmography for continuous heart rate and blood pressure recordings. Time and spectral components of heart rate (HRV) and blood pressure variability (BPV), non‐invasive indices of autonomic function, were analyzed using five‐minute segments at baseline and 5‐minutes post‐resistance exercise.ResultsAt baseline, OA had higher systolic and mean blood pressure, as well as lower root mean square of successive differences (RMSSD), low‐frequency (LF) RRI, high‐frequency (HF) RRI, and baroreceptor sensitivity (BRS) (p<0.05). At 5‐minutes post‐exercise, LF/HF ratio and LF systolic blood pressure increased (p<0.05). RMSSD, HF RRI, and BRS, were greater at baseline for YA and all variables decreased at 5‐min, while older adults did not change over time (interactions, p<0.05).ConclusionsThese results suggest YA exhibited parasympathetic withdrawal 5‐minutes post‐exercise, whereas OA either did not exhibit parasympathetic withdrawal or had already recovered at 5 min post exercise, but this cannot be distinguished from our data. Both groups appear to have elevated sympathetic modulation at 5‐min, as indicated by RRI, LF/HF and LF BPV. Further investigation of the response during exercise is required. However, there are clear differences in autonomic recovery following maximal resistance exercise in OA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.