bluuebunny/crossref_metadata_2025 huggingface dataset:
IGF‐1 deficiency promotes pathological remodeling of cerebral arteries: a potential mechanism contributing to the pathogenesis of intracerebral hemorrhages in aging
Authors: Fulop Gabor A. , Ramirez‐Perez Francisco I. , Kiss Tamas , Tarantini Stefano , Toth Peter , Yabluchanskiy Andriy , Conley Shannon M. , Ballabh Praveen , Martinez‐Lemus Luis A. , Ungvari Zoltan , Csiszar Anna
Published: June 2021

Clinical and experimental studies show that age‐related decline in circulating IGF‐1 levels promotes the pathogenesis of intracerebral hemorrhages, which critically contribute to the development of vascular cognitive impairment and disability in older adults. Yet, the mechanisms by which IGF‐1 deficiency compromises structural integrity of the cerebral vasculature are not completely understood. To determine the role of IGF‐1 deficiency in pathological remodeling of middle cerebral arteries (MCAs), we compared alterations in vascular mechanics, morphology and remodeling‐related gene expression profile in mice with liver‐specific knockdown of IGF‐1 (Igf1f/f + TBG‐Cre‐AAV8) and control mice with or without hypertension induced by angiotensin‐II treatment. We found that IGF‐1 deficiency resulted in thinning of the media and decreased wall‐to‐lumen ratio in MCAs. MCAs of control mice exhibited structural adaptation to hypertension, manifested as a significant increase in wall thickness, vascular smooth muscle cell hypertrophy, decreased internal diameter and up‐regulation of extracellular matrix (ECM)‐related genes. IGF‐1 deficiency impaired hypertension‐induced adaptive media hypertrophy and dysregulated extracellular matrix remodeling, decreasing elastin content and attenuating adaptive changes in ECM‐related gene expression. Thus, circulating IGF‐1 plays a critical role in maintenance of the structural integrity of cerebral arteries. Alterations of VSMC phenotype and pathological remodeling of the arterial wall associated with age‐related IGF‐1 deficiency have important translational relevance for the pathogenesis of ICHs and vascular cognitive impairment in elderly hypertensive patients.

Support or Funding Information

This work was supported by grants from the American Heart Association, the National Center for Complementary and Alternative Medicine, and the National Institute on Aging

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Selective Brain Cooling with Transnasal Flow of Ambient Air for Pediatric Resuscitation
Authors: Koehler Raymond C. , Reyes Michael , Armstrong Jillian S. , Hopkins C Danielle , Kulikowicz Ewa , Tandri Harikrishna
Published: June 2021

Discharge rates and neurologic outcome from out‐of‐hospital pediatric cardiac arrest remains poor. The recent THAPCA trial for out‐of‐hospital pediatric cardiac arrest reported only a small, non‐significant favorable outcome with hypothermic treatment. A major limitation of this study was the median 5.9‐hour delay in inducing hypothermia, as studies in animals show loss of efficacy with this delay in initiation of hypothermia. To minimize this delay, we developed a simple yet innovative technique of transnasal cooling. Air at ambient temperature is passed through standard nasal cannula and out of the mouth to produce evaporative cooling of the nasal passages and a countercurrent heat exchange with cephalic arterial blood. We determined whether an age‐dependent effect exists in the ability to cool the brain because of potential differences in air humidification capacity during development. We studied piglets at 2–5 days of age (1.8 kg; 40 g brain weight), 2 weeks of age (4 kg; 45 g brain weight) and 6 weeks of age (16 kg; 75 g brain weight; adult brain = 110 g). The corresponding nasal turbinate surface area was estimated to be 3176±243, 4847±417, and 8651±1234 mm2. In anesthetized 1.8‐kg piglets with mechanical ventilation and an open mouth to permit airflow exit, institution of nasal airflow of 4 L/min through nasal cannula decreased brain temperature from 38.0±0.4°C to 36.4±0.9, 35.6±1.2, and 34.4±1.7°C at 30, 60, and 120 min, respectively. In 4‐kg piglets, nasal airflow of 32 L/min decreased brain temperature from 38.3±0.3°C to 35.0±0.6, 33.8±0.6, and 31.9±0.6°C at 30, 60, and 120 min, respectively. In 16‐kg piglets, nasal airflow of 32 L/min decreased brain temperature from 38.5±0.4°C to 35.1±1.6, 34.1±1.8, and 32.9±1.6°C at 30, 60, and 120 min, respectively. No further benefit was seen by increasing airflow to 48 L/min. No substantial spatial temperature gradients were seen among the sensory cortex, putamen, thalamus, cerebellum and olfactory bulb in any age group, suggesting that heat transfer is via blood convection rather than direct conduction from the airway wall. Decreases in rectal temperature lagged brain temperature by 30–60 min at all three ages. The rapid and selective brain cooling indicates that a high humidifying capacity of the nasal turbinates is present early in life. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field by emergency medical technicians, in both community hospital emergency rooms, and in low resource areas for early initiation of brain cooling prior to maintenance with standard surface cooling after pediatric cardiac arrest.

Support or Funding Information

Supported by NIH NS095036

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Single Session Mindfulness Meditation Reduces Aortic Pulsatile Load and Anxiety in Mild to Moderately Anxious Adults
Authors: Durocher John J. , Marti Hannah , Morin Brigitte , Wakeham Travis R.
Published: June 2021

Mindfulness meditation has been shown to have numerous health benefits when used over the course of days or weeks, but the effect of a single session on aortic pulsatility and anxiety is unclear. Therefore we sought to determine if a single session of mindfulness meditation could effectively reduce aortic pulsatile load and anxiety. Fourteen adults (24±8 years) with mild to moderate anxiety (≥8 Beck Anxiety Inventory (BAI)) participated in a 60 minute guided mindfulness meditation session. Baseline aortic pulsatile load (aortic pulse pressure × heart rate) and BAI were assessed approximately one week prior to the mindfulness meditation session during a study orientation. Aortic pulsatile load was assessed before, immediately after, and 60 minutes after the mindfulness meditation session. Anxiety was also assessed 60 minutes following meditation. The single mindfulness session reduced aortic pulsatile load from 2008±108 to 1730±85 a.u. immediately after meditation (p<0.01). The reduction in aortic pulsatile load was maintained 60 minutes post‐meditation (1729±99 a.u.; p<0.02). The BAI score was also significantly reduced 60 minutes post‐meditation compared to baseline (15±1 vs. 11±2; p<0.02). Our findings demonstrate that even a single session of mindfulness meditation can have cardiovascular and psychological benefits for adults with mild to moderate anxiety. Reductions in pulsatile load may help to reduce damage to end organs such as the brain and kidneys, while reduced anxiety could help to prevent vascular dysfunction.

Support or Funding Information

Supported by the Portage Health Foundation.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
His and Her Computational Models of Long‐term Blood Pressure Regulation
Authors: Leete Jessica , Layton Anita
Published: June 2021

Hypertension is a global health challenge. Hypertensive men and women are typically treated with the same approach, with less effective outcome in women. To address the critical need to better understand the mechanism of blood pressure control in both men and women, we have developed sex‐specific computational models of long‐term blood pressure control. The model represents sex differences in the kidney's pressure natriuresis response, whereby increases in renal perfusion pressure lead to increases in Na+ excretion; that in turns lowers salt and water retention and reduces effective circulating volume. Females tend to exhibit a leftward shift in the pressure‐natriuresis relation relative to males. The model also includes detailed representation of the renin‐angiotensin aldosterone system (RAAS), a non‐sex hormonal system critical for maintaining blood pressure and effective circulating volume. Major sex differences in the RAAS have been identified, including how substrate is produced and how angiotensin interacts with receptors. Those sex differences are included in the model. Using the developed model, we test the hypothesis that RAAS‐mediated anti‐natriuretic (and thus blood pressure increasing) effects are more severe in males than females, leading to more hypertension‐induced injury in males.

Support or Funding Information

This research was supported in part by the National Institutes of Health: National Institute of Diabetes and Digestive and Kidney Diseases, grant R01DK106102.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Plantago asiatica seed Extracts Alleviated Blood Pressure of Phase I –Spontaneous Hypertension Rats
Authors: Chou Chi‐Chen , Lue Sheng‐I , Fu Yaw‐Syan , Weng Ching‐Feng
Published: June 2021

Introduction and hypothesis

The seed of Plantago asiatica is a traditional Chinese medicine with diuretic and anti‐inflammatory effects. Of note hypertension is a multifactorial cardiovascular disorder involved in variety genetic and environmental factors and it is a major risk factor for heart disease, heart attack or stroke. Phase‐1 hypertension (P1‐HT) is considered to be critical phase in the beginning stage of high blood pressure. In this study, P. asiatica seed extract (PSE) was administrated in spontaneous P1‐HT rats to evaluate the efficacy of antihypertension.

Methods

In this study, arterial pressures of each P1‐HT rats were recorded for 5 minutes by intravascular femoral artery catheter served as a reference value for prior to treatment. In acute antihypertensive effect test, P1‐HT rat gavage received 0.36 g/kg Bwt of PSE or equal volume of water by dissolved in distilled water and the arterial pressures were recorded continuously for 1 hr. In chronic antihypertensive effect test, P1‐HT rats gavage received 0.36 g/kg Bwt day of PSE or equal volume of water for 4 weeks. Students–t test and one way ANOVA were used for statistical analysis. Statistical significances were set at a P< 0.05.

Results

Firstly, the monitor of rat blood pressure was confirmed that the systolic, diastolic and mean arterial pressures of this spontaneous P1‐HT rat are stably keeping in 150±20 mmHg, 92±30 mmHg, and 115±15 mmHg, respectively. The acute antihypertensive effects of this new breeding spontaneous P1‐HT rat could appear within 15 min. after PSE oral administration and lasting more than 1 hr. This acute antihypertensive effect of PSE could decrease the systolic pressure of P1‐HT rat for 28 mmHg, and diastolic pressure for 16 mmHg when simultaneously compared with verapamil as a reference drug, but there were no significant difference in the pretreated reference value of both acute PSE and the control treated groups of P1‐HT rat. The reducing tendency of blood pressure was also found in 4 weeks PSE treatment as compared with the untreated control.

Conclusions

This new breeding P1‐HT modeling rat has a stable phase‐1 hypertensive phenotype after sexually mature and it is suitable for use in hypertensive studies. The oral administration with PSE can effectively reduce blood pressure within a quarter and last more than 1 hr while taking PSE daily can control the severity of hypertension.

Support or Funding Information

MOST‐104‐2320‐B‐259‐001‐MY3

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 Glucagon‐Like Peptide‐1 Receptor Agonist (GLP1RA) on Hypertension‐Induced Atrial Remodelling
Authors: Zhang Zhe Yu
Published: June 2021

Introduction

Atrial fibrillation (AF) is one of the most important cause of stroke. Hypertension (HT)‐induced atrial remodelling is the most common risk factor for AF. Studies have shown that patients receiving GLP‐1 receptor agonist have reduced AF. This study investigates the effect of GLP1RA on AF prevention.

Method

HT was induced in 15 swines using angiotensin II infusion. At 8 weeks (8W) GLP1RA was randomly given to the swines for 8W in 1:2 ratio. Effect of GLP1RA of atrial remodelling was assessed at 0W, 8W and 18W.

Results

At 0W and 8W, there were no differences in body weight, blood pressure, interventricular septal thickness at diastole (IVSDD), left ventricular end‐diastolic pressure (LVEDP), −dP/dt or end‐diastolic pressure volume relationship (EDPVR) between the treatment (n=5) and control (n=10) group. At 18W, there were no significant differences in body weight (78.2±2.26kg vs 80.4±2.67kg, P=0.558), SBP (144±5.1 mmHg vs 169.2±7.3 mmHg, P=0.229) or DBP (94±5.1 mmHg vs 105.3±5.6 mmHg, P=0.520) between the two groups. Nevertheless, IVSDD (0.96±0.09 mm vs 1.19±0.03 mm, P<0.05), LVEDP (8±0.86 mmHg vs 10±1.14 mmHg, P<0.05), −dP/dt (−943.6±94.7 vs −1387.5±58.4, P<0.05) and EDPVR (0.224±0.04 vs 0.434±0.03, P<0.05) were significantly lower in the treatment group. Biomarker study also showed a reduced TGF‐b1 (178.9±7.6pg/mL vs 348.5±24.1pg/mL, P<0.05) and sICAM‐1(0.823±0.56 ng/mL vs 2.308±0.378 ng/mL, P<0.05) in the treatment group. Serum TNF‐a (36.92±0.81 pg/mL vs 56.03±2.66 pg/mL, P<0.05), ROS (13.86±3.8 uM vs 30.27±13.9 uM, P<0.05) and MMP‐2 (19.08±0.39 ng/mL vs 28.16±0.42 ng/mL, P<0.05) expression were all significantly lower in the treatment compared with control group.

Conclusion

GLP1RA halted the progression of HT‐induced LV functional and structural remodeling independent of body weight or blood pressure but associated with reduced profibrotic markers, inflammatory markers and oxidative stress.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Nephron‐wide deletion of NOS3 impairs salt excretion and causes hypertension during high salt intake via altered NKCC2 activity
Authors: Gao Yang , Stuart Deborah , Takahishi Takamune , Kohan Donald E.
Published: June 2021

In vitro studies suggest that nephron nitric oxide synthase (NOS3) regulates urinary Na+ excretion (UNaV) and blood pressure (BP). To assess whether NOS3 is indeed involved in the physiological regulation of UNaV and BP, mice with doxycycline‐inducible nephron‐wide deletion of NOS3 were generated. These mice were homozygous for loxP‐flanked exons 9–12 of the NOS3 gene (contains the calmodulin binding site) and hemizygous for Pax8‐rtTA and LC‐1 transgenes (Pax8 promoter‐rtTA confers nephron‐specific targeting and LC‐1 transgene contains doxycycline/rtTA‐inducible Cre recombinase). Mice were treated with either vehicle (controls) or doxycycline (knockouts, KO) at 1 month of age for 12 days and studied at ~3 months of age. Nephron‐specific NOS3 KO mice had renal‐specific NOS3 gene recombination, reduced NOS3 mRNA levels in microdissected nephron segments, and decreased urine NOx excretion. In response to chronic high salt load, KO mice had increased mean arterial pressure (103 ± 2 mmHg in controls and 118 ± 3 mmHg in KO, N=6, p<0.05), reduced renal NOS3 protein expression (43 ± 8.4% of controls, N=5–6, p<0.05), and enhanced cumulative Na+ retention. In response to acute salt load (1.5 ml saline i.p. injection), KO mice had delayed urinary Na+ excretion vs. controls; this delayed UNaV was abolished by furosemide, but not hydrochlorothiazide or amiloride. After 4h of an acute salt load, KO mice had decreased NOS3 protein expression (19 ± 6.5% of controls, N=5–6, p<0.05) and an increased ratio of phosphorylated/total NKCC2 (162 ± 14.1% of controls, N=5–6, p<0.05). No differences in NHE3, NCC (phosphorylated/total), or ENaC isoforms were noted 4 h after an acute salt load or after chronic salt loading. No sex‐dependent differences in UNaV or BP were observed. In summary, these findings support the notion that nephron NOS3 is involved in acute and chronic control of renal Na+ excretion and BP during high salt intake. Thick ascending limb NKCC2 may be the major transporter involved in nephron NOS3 regulation of renal Na+ excretion and BP.

Support or Funding Information

This research was supported by NIH P01 HL095499

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reduced Arrhythmogenic Potential of Ventricular Paired Pacing During Myocardial Infarction
Authors: Stein Paul M.
Published: June 2021

Since the 1960's, the clinical use of ventricular paired pacing (VPP), a form of continuous postextrasystolic potentiation, to augment cardiac function in cardiogenic shock has been prevented by the stigma of ventricular arrhythmogenesis. Historically, this perception was based on very limited human data on the sickest of the sick when many current medical treatments were long into the future. One such treatment is the use of β‐adrenergic receptor blockade, well accepted now, but antithetical then. A meta‐analysis of canine studies of myocardial infarction was performed to understand the effect β‐blockade had on the incidence of ventricular fibrillation during the VPP treatment (References: Singer, D. H. et al. Bull. N. Y. Acad. Med. 41: 652–669, 1965; Rothfeld, E. L. et al. Am. J. Cardiol. 23: 224–228, 1969; Karayannacos, P. E. et al. Ann. Thorac. Surg. 27:34–41, 1979). Infarctions in 48 animals were produced through ligation of the entire or one to three branches of the left anterior descending coronary artery or the entire left circumflex coronary artery with (n=24) or without i.v. pronetholol or propranolol (n=24). Following ligation, in all studies, VPP had a marked inotropic effect. Without β‐blockade, 16 went into ventricular fibrillation during VPP, while only 5 with β‐blockade did.

Statistics

Comparison of Proportions Difference=45.83%, 95% Confidence Interval=15.21–68.22, χ2 = 10.03, P<0.002, Contingency Coefficient=0.42;

Odds Ratio=7.60, 95% Confidence Interval=2.07–27.90, z Statistic=3.06, P<0.005;

Relative Risk=3.20, 95% Confidence Interval=1.40–7.34, z Statistic=2.75, P<0.01;

Number Needed to Treat=2.18, 95% Confidence Interval=4.78–1.41.

In conclusion, while not eliminating the potential for induced ventricular fibrillation, the anti‐arrhythmic effect of β‐adrenergic receptor blockage did significantly reduce the incidence from 67% to 21%, a 69% decrease. A clinical trial is necessary to confirm these findings under today's medical landscape, when many heart attack victims are already taking β‐blocking drugs and standard cardiogenic shock therapy includes the powerful anti‐arrhythmic drug amiodarone. Until then, ventricular paired pacing should not be categorized as overtly arrhythmogenic in cardiogenic shock. It does, however, contain a minor potential that must be carefully watched for with ubiquitous defibrillators.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Day 1 Post‐Myocardial Infarction Cardiac Macrophage Transcriptomic Signatures that Link to LV Infarct Wall Thinning
Authors: Mouton Alan Joseph , Ma Yonggang , DeLeon‐Pennell Kristine , Garrett Michael , Lindsey Merry
Published: June 2021

We evaluated the relationships between the macrophage transcriptome at day 1 following myocardial infarction (MI) and infarct wall thinning. C57BL/6J male mice (3–6 months old) were subjected to permanent coronary artery ligation to induce MI, and macrophages were isolated from the infarct region at day 1 post‐MI. Day 0 no MI cardiac macrophages served as the negative control. Whole transcriptome analysis was performed using next‐generation RNA sequencing (Illumina NextSeq 500 platform) on n=4 pooled sets for each time, representing a total of 59 mice. Infarct wall thinning (Day 0 – Day 1) was assessed by echocardiography. A total of 16,696 genes were quantified and passed quality control (FPKM > 0 for at least 3 replicates per group). Of these, 3,062 were differentially expressed (fold change ≥ 2.0, p<0.05), of which 1,019 were upregulated and 2,043 were downregulated. Gene ontology pathways enriched for the upregulated genes included inflammatory response and response to hypoxia, while pathways enriched for the downregulated genes included extracellular matrix organization. To determine potential contributions of individual genes to the wall thinning phenotype, large scale correlation analysis was performed. Of the 3,062 differentially expressed genes, 119 positively correlated with the decrease in wall thickness, while 93 negatively correlated. Of interest, positive correlations between several pro‐inflammatory genes and wall thinning were observed, includingTlr1 (r=0.99, p=0.01), Tnfrsf1b (r=0.95; p=0.047), Hrh4 (r=0.96; p=0.036), and Stat5a (r=0.95; p=0.048), all of which play pro‐inflammatory roles in response to inflammatory stimuli. Genes that negatively correlated with wall thinning included Vegfa (r=−0.96, p=0.04) and Nfkbie (r=−0.99, p=0.009), which are negative regulators of inflammation. Of the positively correlated genes, NF‐kappaB was a major enriched pathway (p=0.009), suggesting excessive NF‐kappaB signaling in macrophages exacerbates post‐MI wall thinning. For negatively correlated genes, Kit signaling, which has been linked to immune suppression and the anti‐inflammatory M2 phenotype, was a major enriched pathway (p=0.00001). Combined, these results indicate that promoting pro‐inflammatory and limiting anti‐inflammatory gene expression in post‐MI day 1 cardiac macrophages is directly linked to LV wall thinning.

Support or Funding Information

Funding: NIH GM103328, GM103476, GM104357, GM114833, GM115428, HL051971, HL075360, HL105324, HL129823, AHA 15SDG22930009, and VA 5I01BX000505 and IK2BX003922

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Previously Exercise Training in Ovariectomized Rats Prevents Inflammatory Status of Myocardial Infarction by Vagal Tonus Increase
Authors: Ruberti Olivia Moraes , de Paula Eunice Mendonça , Souza Andressa Silva , Viana Laís Rosa , Delbin Maria Andreia , Rodrigues Bruno
Published: June 2021

The aim of this study was to investigate the preventive effects of aerobic training (AT) in ovariectomized rats submitted to myocardial infarction (MI). Female Wistar rats were ovariectomized and divided into four randomized groups: sedentary sham (SS), sedentary + MI (SI), AT + sham (TS), AT + myocardial infarction (TI). Exercise training was performed on a treadmill (60 to 75% of the maximum running speed) in ovariectomized rats before the MI. After 8 weeks of AT, the MI area was lower in the TI group compared to SI. The sympathetic tonus was reduced in TS (68±3 bpm) and TI (77±3 bpm) groups as compared to SI (98±4 bpm), but higher in TI compared to TS. The vagal tonus was substantially increased in TI (40±4 bpm) in comparison to SI (23±3 bpm). The AT reduced inflammatory cytokines profile on left ventricle, as interleukin‐6 (IL‐6: 68.2±7.2 vs. 148.9±6.1 pg/mg prot), IL‐1β (86.7±10.2 vs. 135.9±12.2 pg/mg prot), interferon‐γ (19.3±3.3 vs. 38.7±4.3 pg/mg prot) and tumor necrosis factor‐α (TNF‐α: 19.6±3.8 vs. 42.3±5.8 pg/mg prot), as well as increased IL‐10/TNF‐α ratio in TI rats as compared to SI. Vagal tonus was negatively correlated with TNF‐α (r=−0.75; P<0.001) and positively associated to interleukin‐10 (r=0.77; P<0.001). These findings indicate that AT displayed ventricular protective effects on the ovariectomized rats submitted to MI. Additionally, protective effects regarding left ventricle inflammatory status may have occurred in the light of cholinergic anti‐inflammatory pathway.

Support or Funding Information

CAPES, FAPESP and CNPq

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Myocardial ischemia/reperfusion in rats: characterization of cardiac injuries
Authors: Omoto Ana Carolina Mieko , Gava Fábio Nelson , Fazan Frederico Sassoli , Silva Carlos Alberto Aguiar , Silva Hadder Batista , Nappi Camilla Rizzo , Parente Juliana Montenegro , da Costa Rafael Menezes , Salgado Helio Cesar , Fazan Rubens
Published: June 2021

Coronary reperfusion is an important tool to limit infarct size and preserve cardiac function after acute myocardial infarction. However, the reperfusion of acutely ischemic myocardium can induce arrhythmias and cardiomyocyte death, a phenomenon known as myocardial reperfusion injury. The study of the mechanisms and the search for therapies to protect the heart from reperfusion injury is an important field of research. The aim of this study was to evaluate mophofunctional and molecular aspects involved in a rat model of acute myocardial ischemia followed by reperfusion (IR). Male Wistar rats (N=47) were anesthetized with ketamine and xylazine (50 and 10 mg/kg, ip) and subjected to myocardial IR by temporary (30 min) ligation of left descending coronary artery. Control rats (N=7) underwent the same surgery without coronary ligation. After 4 weeks 45% of the rats subjected to IR showed no cardiac lesion (NL) while 38% presented mild (ML) and 17% large (LL) lesion of the heart. Cardiac function, evaluated by echocardiography, was impaired in all rats subjected to IR, independently of the degree of cardiac lesion. Interstitial fibrosis, quantified in non‐infarcted myocardium, was 11±0.8% in control rats and was found increased in rats with IR (19.7±1.4, 19.4±1.2 and 21.6±1.2% in rats with NL, ML and LL, respectively). Activity of matrix‐metalloproteinase‐2 was higher in the myocardium of rats subjected to IR (0,44 to 0.48 AU) as compared to their control counterparts (0.22 AU). Moreover, concentration of superoxide anion in the myocardium of rats subjected to IR was higher (176±44, 127±13 and 108±30 RLU/mg of protein in rats with NL, ML and LL, respectively) as compared to their controls (50±5 RLU/mg of protein). Finally, hydrogen peroxide was measured 86±29 nmol/mg of protein in myocardium of control rats and was found markedly higher (1077±192, 1194±238 and 639±117 nmol/mg of protein in IR rats with NL, ML and LL, respectively) in the animals subjected to IR. These results show that IR leads to distinct degrees of myocardial injury in a rat model, which contributes to cardiac dysfunction over time. Reactive oxygen species (O2− and H2O2) and MMP‐2 seems to be involved in cardiac dysfunction and heart failure development after reperfusion.

Support or Funding Information

Financial support: CNPq (870308/1997‐1) e FAPESP (2013/20549‐7).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CD8 T‐cells have a biphasic role during post‐myocardial infarction cardiac remodeling
Authors: DeLeon‐Pennell Kristine Y. , Lindsey Merry L. , Flynn Elizabeth , Menick Donald R.
Published: June 2021

Historically, the role of adaptive immunity has not been considered to play a major role in the wound healing response to myocardial infarction (MI), due to the low number of these cells within the infarct region. While recent studies have linked elevated CD8+ T‐cell counts (>1065 cells/mm3) with a 2‐fold decrease in post‐MI survival in humans, the exact mechanisms by which CD8+ T‐cells impair cardiac wound healing post‐MI are not thoroughly understood. We hypothesized that CD8+ T‐cells regulate the inflammatory response leading to decreased survival and cardiac function post‐MI. We performed permanent occlusion of the left anterior descending coronary artery on C57BL/6J wild‐type mice (WT; 4.5±0.1 months of age; n=6 males and females) and CD8atm1Mak mice (Null; 4.1±0.2 months of age; n=6 males and females) that are deficient in functional cytotoxic T‐cells. Null had improved day 7 survival (75%) compared to WT (43%; p<0.0001). Interestingly, 100% of Null who died did so due to cardiac rupture of the left ventricle (rupture/total deaths; 2/2) whereas only 38% of WT (3/8; p<0.0001) died of cardiac rupture. In addition, Null died during the early post‐MI phase (at days 1–2). Post‐MI mortality in WT does not usually occur until after day 3, suggesting CD8+ T‐cells may be protective during the early post‐MI phase by limiting immediate remodeling. Echocardiography measured at day 7 post‐MI showed improved cardiac physiology, as indicated by fractional shortening in Null (11±3%) compared to WT (4±1%; p<0.05) implicating CD8+ T‐cells as a negative regulator of wound healing during the later phase post‐MI. In conclusion, our data suggests CD8+ T‐cells play a biphasic role during post‐MI cardiac remodeling by being protective early and detrimental later.

Support or Funding Information

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Small molecule inhibition of protein phosphatase 2A in vivo does not disrupt glucose homeostasis in mice.
Authors: Lee Juyeon , Bharath Leena P. , Kim Ji‐Seok , Cho JaeMin , Park Seul‐Ki , Ruan Ting , Symons J David
Published: June 2021

Identifying new targets for therapeutic intervention that might attenuate cardiovascular complications associated with type 2 diabetes is needed. Earlier we reported that mice treated with a potent and selective small molecule inhibitor (LB1; Lixte Biotechnology Holdings, Inc., East Setauket, NY; 1 mg/kg IP) of protein phosphatase 2A (PP2A) for the last 14 days of an obesogenic diet (12 weeks of fat‐feeding) did not display vascular PP2A hyperactivation, endothelial dysfunction, or hypertension that otherwise developed in fat‐fed mice treated with vehicle (Bharath et al, Diabetes, 2015). We concluded that PP2A hyperactivation should be considered further as a therapeutic target for intervention. Results from another laboratory group indicated that 2 mg/kg LB1 IP (3 hours) evoked hyperglycemia, glucose intolerance, and hepatic glycogen depletion in chow‐fed and fat‐fed (3 days) rats. The authors concluded that targeting PP2A hyperactivation should not be considered as a therapeutic intervention. Based on the incongruent conclusions from the two studies we tested the hypotheses that LB1 treatment for 14‐days impairs: (i) peripheral glucose homeostasis; (ii) hepatic glycogen content; and (iii) insulin‐mediated signal transduction in the liver. To test the first two hypotheses, 7‐week old male C57BL/6J mice consumed standard (Con) or high fat (HF) chow for 12 weeks. Subgroups of Con and HF mice received 1 mg/kg LB1 or saline (Veh) IP for the last 14 days. First, glucose and insulin tolerance testing indicated that LB1 treatment does not impair peripheral glucose homeostasis in Con mice or HF mice. Second, LB1 treatment did not lower hepatic glycogen content, p‐Akt2S474/Akt2, p‐Gsk3ɑS21/Gsk3ɑβ, or p‐GSS641/GS, in lean or obese mice under basal, random‐fed conditions. To test the third hypothesis, age‐matched male mice that consumed standard chow were treated with LB1 or Veh for 14 days. On day 15, after a 6 h fast, insulin or saline was administered (i.v.) to anesthetized mice, and segments of liver were collected to assess p‐Akt2S474/Akt2, p‐GSK3ɑS21/GSK3ɑ, and p‐GSS641/GS. Insulin‐mediated signal transduction in the liver was similar regardless of LB1 treatment. We conclude that LB1 treatment in mice for 14‐days does not impair: (i) peripheral glucose homeostasis; (ii) hepatic glycogen content; or (iii) insulin‐mediated signal transduction in the liver.

Support or Funding Information

American Diabetes Association (ADA: 1‐12‐BS‐208, ADA 7‐08‐RA‐164) and National Institutes of Health (NIH: 2R15HL091493) to JDS

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Central and Peripheral Body Fat Distribution on Insulin Resistance of Young Obese Women
Authors: Lopes‐Vicente Wanda R. P. , Cepeda Felipe X. , Hussid Maria Fernanda , Silva Leslie Virmondes , Alves Cléber R. , De Moura José Roberto , Consolim‐Colombo Fernanda M. , Tinucci Tais , Trombetta Ivani C.
Published: June 2021

Studies have shown that excess of fat in central region is the main substrate for pathophysiological alterations that leads obesity‐associated insulin resistance. Lately, in the medical practice the use of the waist circumference (WC) instead waist‐to‐hip ratio (WHR) is more usual. We hypothesized that WHR is a better tool to infer insulin resistance in young obese women. The aim of this study was to evaluate the insulin‐sensitive/insulin‐resistant in young obese women within central and peripheral body fat distribution. We studied 61 young obese women (BMI 30 to 40 kg/m2) with WC ≥ 88 cm and without comorbidities. They were divided into: with central fat distribution (CF), defined as waist‐to‐hip ratio (WHR) ≥ 0.85 cm (n=30, 33±7 y), and with peripheral fat distribution (PF) with WHR < 0.85 cm (n=31, 33±6 y). All volunteers were submitted to anthropometric, glycemic and insulin measurements and indexes: fasting, HOMA‐IR, QUICKI and area under the curve (AUC) during the Oral Glucose Tolerance Test (OGTT) to assess the insulin sensitivity. Despite the fat distribution, CF and PF shown similar anthropometric measures (weight= 86.8±8.5 vs.87.6±8.3 kg, WC= 109±6 vs.106±8 cm, BMI= 33.2±2.7 vs. 33.7±2.4 kg/m2; respectively, p>0.05). Also, both obese groups, CF and PF, showed normal fasting glucose (84±10 vs. 82±10 mg/dL, p=0.420), based in the IDF criteria (<100mg/dL). However, the group CF compared with PF presented elevated fasting insulin (17.8±8.2 vs. 12.6±6.8 uUI/mL, p=0.008), HOMA‐IR (3.7±1.9 vs. 2.6±1.6 uUI/mL, p=0.011), reduced QUICKI (0.322±0.025 vs. 0.340±0.025, p=0.007). Furthermore, the group CF compared with PF had lower insulin sensitivity as AUCglucose/AUCinsulin ratio from OGTT (1.42±0.67 vs. 2.12±0.86, p=0.001). In conclusion, our data demonstrated that in young obese women with similar WC and fasting glucose, the central body fat distribution increase insulin‐resistant, emphasizing the importance in used the waist‐to‐hip ratio as important tool for identify the additional risk factor in obesity young women.

Support or Funding Information

#Universidade Nove de Julho (UNINOVE), SP ‐ Brazil.

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 Isolated Muscle Training on Vasomotor Response and Peripheral Blood Flow
Authors: Bisconti Angela Valentina , Venturelli Massimo , Cè Emiliano , Longo Stefano , Fantauzzi Alessia , Esposito Fabio
Published: June 2021

The vasomotor response, a marker of cardiovascular health, refers to the adaptability of the inner lining of blood vessels to maintain the homeostasis of vascular tone. The two main control systems that underpin this response are: the systemic autonomic control, with the sympathetic branch mediated vasoconstriction, and the endothelial cells response to mechanical and chemical stimuli, that results in smooth muscles cell vasodilation. During exercise the peripheral circulation is mostly mediated by local control, and the peripheral blood flow (BF) increases in all body districts directly involved and not involved by physical exercise. The vasodilation response depends on the magnitude of the stimulus received. To date, vascular adaptations in the brachial artery not involved in an isolated leg muscle training, is still unclear/unknown. Repetitive changes in BF occurring during exercise training may act as vascular training for vessels supplying the active muscle bed and ones distal to the active muscle. Therefore, the study aim was to evaluate the effects of isolated quadriceps muscle training (IQT) on vasomotor response in the lower limb directly involved with exercise (femoral artery) and on the upper limb, not involved with IQT (brachial artery). Ten healthy participants (4 M and 6 F; 23±3 yrs) underwent eight weeks of IQT (3 days/week; ~ 40 min; 50 – 90% WRM) at different intensities. Maximum work rate (MWR) was assessed before, during (every 2 weeks, to redefine the training work‐load) and after IQT. Pre‐ and post‐IQT measurements of vascular function and peripheral BF were performed by flow mediated dilatation (%FMD) in the brachial artery (non‐trained limb), and by passive limb movement in femoral artery (trained limb). After 8 weeks of IQT, MWR and BF in femoral artery increased significantly by 43% and 153%, respectively. No difference in %FMD was found despite 21% increase in brachial artery blood flow during exercise was found. Eight weeks of IQT improved peripheral vasomotor response only in the lower limb directly involved in IQT without affecting vascular functionality in the uninvolved upper limb, suggesting that IQT did not provide a sufficient stimulus to induce adaptations also in other districts' vasculature.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Workplace Standing Desks and Arterial Stiffness
Authors: Greenlund Ian M. , Kimmes Piersan E. , Wang Min , Durocher John J.
Published: June 2021

At least 1 in 4 American adults are classified as sedentary. Sedentary behavior is a contributing factor to many diseases such as cardiovascular disease and type II diabetes. Sedentary behavior and age are known contributors to arterial stiffness, but it is unknown if prolonged standing at work could help to reduce arterial stiffness. Therefore, we examined 48 individuals (40 women; 8 men) who primarily sit at work (n=24, age: 41±1 years, BMI: 25±1 kg/m2), or primarily stand at work (n=24, age: 45±2 years, BMI: 25±1 kg/m2). Arterial stiffness was assessed as pulse wave velocity (PWV) through applanation tonometry and electrocardiography. Aerobic fitness was estimated via a Rockport walk test and regional body fat was measured with bioelectric impedance. Analysis of covariance was performed to determine if PWV was different between those who consistently sit at work vs. those who consistently stand at work. Age, fitness, and regional fat percentage were used as covariates. Carotid‐femoral PWV (cfPWV) was not different between sitting and standing (6.6±0.3 vs. 6.9±0.3 m/s), or when normalized to aortic mean arterial pressure (aMAP) (0.0816±0.003 vs. 0.0789±0.002 ms−1 * mmHg−1). Likewise, leg PWV was similar between sitting and standing (9.0±0.3 vs. 8.8±0.3 m/s). Therefore, we used stepwise regression to determine the best explanatory variable for cfPWV, cfPWV/aMAP, and leg PWV. The strongest predicting variables for cfPWV and cfPWV/aMAP were age (p<0.001; p=0.002) and trunk fat percentage (p=0.063; p=0.039), respectively. However, the strongest predictors of leg PWV were leg fat percentage (p=0.051) and fitness (p=0.159). In conclusion, prolonged standing at work does not appear to alter arterial stiffness when controlling for important covariates such as age, fitness, and regional fat percentage. Our findings are in agreement with other studies indicating the influence of age on arterial stiffness, and indicate regional fat percentage may help to predict PWV.

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 AmLexin (Acacia catechu & Morus alba) on Redox Balance and Subjective Pain in Healthy Runners
Authors: Talbott Shawn M. , Talbott Julie A. , Hantla Don
Published: June 2021

Introduction

Intense exercise is known to increase both oxidative stress and post‐exercise pain. Muscle soreness and soft tissue pain is a frequent complaint among recreational exercisers and a significant obstacle to continued participation in regular physical activity.

Objective

Our study examined the effects of an herbal dietary supplement (AmLexin; combination of Acacia catechu heartwood extract and Morus alba root bark extract) versus a look‐alike placebo on redox balance (plasma oxidative stress and oxidative capacity) and subjective pain levels following intense exercise.

Subjects & Methods

Twenty‐four (N=24) healthy men and women were recruited to participate in a progressive 8‐week running program followed by a 13.1‐mile timed run (half‐marathon). Subjects were randomly divided in double‐blind fashion to receive either the supplement at 200 mg b.i.d. (N=12) or placebo (N=12) for 9 weeks (8 weeks pre‐race during training and 1‐week post‐race). We measured range of motion (ROM) and pain/stiffness (WOMAC & VAS) weekly during 8‐weeks of training and daily for 6‐days post‐race, and plasma redox status on days 1 and 6 post‐race.

Results

Due to large variations in ROM between and within subjects, there were no significant differences in ROM between supplementation groups. However, multiple measures of pain and stiffness were significantly lower for days 1–3 post‐race in the AmLexin group compared to the Placebo group, including WOMAC scores for overall pain at day 1 and 3 post run and a clear trend of less stiffness and better activities of daily living in the AmLexin group. The AmLexin group also showed statistically significant less pain/stiffness than Placebo based on VAS scores for multiple body parts (quadriceps, calves, hamstrings, and knees) at several time points after the race. Redox balance assessment indicated the AmLexin group to show a strong trend toward improved status at day 1, that reached statistical significance for lower oxidative stress and higher oxidative capacity at day 6 post‐race compared to the Placebo group.

Conclusion

AmLexin has previously been reported to protect joint cartilage from damage, reducing the amount of glycosaminoglycan released by articular cartilage (1 &2), and to be an effective quencher of super oxide anion, a free radical generated by tissue wear and tear (3). These clinical results further demonstrate AmLexin's effectiveness to reduce oxidative stress, improve oxidative capacity, and prevent the development of post‐exercise subjective pain and stiffness in a population of healthy non‐arthritic adults. Therefore, AmLexin may be viewed as an effective dietary supplement to facilitate healthy pain‐free participation in regular physical activity.

Support or Funding Information

Funding provided by Unigen

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 the high pressure processed rice intake during interval walking training on glycemic control and NFKB2 gene methylation in lifestyle‐related disease patients
Authors: Aida Takamichi , Masuki Shizue , Uchida Koji , Manabe Kazumasa , Morikawa Mayuko , Furihata Mayuka , Fujita Tomoyuki , Nose Hiroshi
Published: June 2021

Background

The rice processed with high pressure before being polished reportedly maintains key nutritional components of brown rice; GABA and polyphenols. In this study, we examined whether the high pressure processed rice (HPPR) intake during interval walking training (IWT) improved the symptoms of lifestyle‐related diseases with enhanced methylation of the NFKB2, a master gene of inflammatory responses.

Methods

Thirty subjects (~70 yr) who had been performing IWT for >6 mos but with higher fasting blood glucose (FBG) (FBG >110 mg/dl or HbA1c >6.2%) and blood pressure (>130 and/or >85 mmHg for systolic and diastolic pressure, respectively) participated in the study. They were randomly divided into two groups consuming either HPPR (n=15) or white rice (WR, n=15). They performed IWT for further 4 months during which period they were instructed to ingest 75 g of HPPR or WR per serving at every breakfast and dinner. Before and after the IWT for 4 months, BG was continuously measured with glucose electrode placed in the abdominal subcutaneous tissue (CGM method) for 6 days, and on the 5th day of the 6 days, all subjects were provided with standardized meals to examine whether glycemic control after meal intake was improved. In addition, blood samples were collected to determine the methylation of the NFKB2 by pyrosequencing method.

Results

After IWT, the average FBG measured in sampled blood before breakfast for 5 days (days 2–6) decreased in HPPR (P=0.021) with decreased variability for 24 hrs measured by the CGM method (P=0.048). Also, the transient increase in BG over 3 hrs after breakfast on the 5th day decreased in HPPR (P=0.022); however, none of these improvements occurred in WR (all, P>0.5). The improvements in glycemic control in HPPR were accompanied by higher methylation of the NFKB2 in HPPR than WR (P=0.045). On the other hand, no effects of HPPR on blood pressures were observed (P>0.4).

Conclusion

HPPR intake during IWT enhanced the improvement of glycemic control with enhanced NFKB2 gene methylation in lifestyle‐related disease patients.

Support or Funding Information

This study was supported by a grant from the National Agriculture and Food Research Organization (SE17).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.