bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibitory Effect of Total Ginsenoside on Pulmonary Fibrosis Induced by Bleomycin is involved in Matrix Metalloproteinase
Authors: Deng Jiang , Chen Pan‐pan , Luo Min , Yang Lu , Shi Wan‐lan 
Published: June 2021

Pulmonary fibrosis is a refractory disease of the respiratory system. As the active components of Panax ginseng, total ginsenoside (TG) have been reported to have antioxidant, anti‐inflammatory and immune modulatory activity. We previously showed that TG has protective effect on pulmonary fibrosis. The purpose of the study was to investigate whether the mechanism of TG against pulmonary fibrosis is involved in the regulation of matrix metalloproteinase (MMPs). The pulmonary fibrosis model of BALB/c mice was replicated by injecting BLM into the trachea. TG (40, 80, 160 mg/kg/day) were given for 28 consecutive days after surgery. Pulmonary fibrosis was determined by measuring lung coefficient, Haematoxylin and Eosin (HE) staining, Masson's trichrome staining, and expression of the alpha smooth muscle actin (α‐SMA, a gene related to pulmonary fibrosis) in lung tissues. Real‐time quantitative PCR and western blot were used to detect matrix metalloproteinase‐2 (MMP‐2), matrixmetalloproteinase‐9 (MMP‐9) and tissue inhibitor of metalloproteinase‐1 (TIMP‐1) mRNA and protein levels respectively. In the present study, TG (40, 80, and 160 mg/kg/d) treatment could evidently ameliorate pulmonary fibrosis and down‐regulate the expression of MMP‐2, MMP‐9 and TIMP‐1 mRNA and protein levels in BLM‐treated mice. The protective effect of TG on bleomycin induced pulmonary fibrosis in mice is related to the regulation of matrix metalloproteinases.Support or Funding InformationThis research was supported by the Social Program for Tackling Key Problems of National Natural Science Foundation of China (NO.81360660 and 81860732.)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Type II Diabetes Mellitus in the Goto‐Kakizaki Rat Impairs Microvascular Function and Contributes to Premature Skeletal Muscle Fatigue
Authors: Frisbee Jefferson , Lewis Matthew , Kasper Jonathan , Chantler Paul , Wiseman Robert 
Published: June 2021

Despite extensive investigation into the impact of metabolic disease on vascular function and, by extension, tissue perfusion and organ function, interpreting results for specific risk factors can be complicated by the additional risks present in most models. To specifically determine the impact of type II diabetes without obesity on skeletal muscle microvascular structure/function, and on active hyperemia with elevated metabolic demand, we used 17‐week old Goto‐Kakizaki rats (GK) to study microvascular function at multiple levels of resolution. Gracilis muscle arterioles demonstrated blunted dilation to acetylcholine (both ex vivo proximal and in situ distal arterioles) and elevated shear (distal arterioles only). All other alterations to reactivity appeared to reflect compromised endothelial function associated with increased TxA2 production and oxidant stress/inflammation rather than alterations to vascular smooth muscle function. Structural changes to the microcirculation of GK were confined to reduced microvessel density of ~12%, with no evidence for altered vascular wall mechanics. Active hyperemia with either field stimulation of in situ cremaster muscle or electrical stimulation via the sciatic nerve for in situ gastrocnemius muscle was blunted in GK; primarily due to blunted functional dilation of skeletal muscle arterioles. The blunted active hyperemia was associated with impaired oxygen uptake (VO2) across the muscle and an accelerated muscle fatigue. Acute interventions to reduce oxidant stress (TEMPOL) and TxA2 action (SQ‐29548) or production (dazmegrel) improved muscle perfusion, VO2, and muscle performance. These results suggest that T2DM in GK impairs skeletal muscle arteriolar function apparently early in the progression of the disease and potentially via an increased ROS/inflammation‐induced TxA2 production/action on network function as a major contributing mechanism.Support or Funding InformationAmerican Heart Association and National Institutes of Health (USA); Canadian Institutes for Health Research and Natural Sciences and Engineering Research Council (Canada)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Impact of analgesics on macro‐ and microcirculatory responses to hemorrhage
Authors: Xiang Lusha , Calderon Alfredo S , Connor Brian S , Hinojosa‐Laborde Carmen , Ryan Kathy L 
Published: June 2021

BACKGROUNDPeripheral vasoconstriction in responseto hemorrhage is critical for blood pressure compensation and vital organperfusion. Opiates and ketamine have been demonstrated to have direct vasoactive effects, but effects on peripheral vasoconstriction response to hemorrhage are unknown for these analgesics. We hypothesize that opioid(fentanyl) impairs blood pressure compensation following hemorrhage due toblunted peripheral vasoconstriction, while ketamine preserves pressure compensation and vasoconstriction.METHODSprague Dawley rats(11–13wk) were randomly assigned to saline (control), fentanyl, or ketamine‐treated groups (n = 9 for each group). Rats were anesthetized within actin and the spinotrapezius muscles were prepared for microcirculatory observation. The arcade arterioles were topically challenged with saline, fentanyl, or ketamine at concentrations relevant to analgesic doses and vascular responses were recorded. After procedurally‐challenged arteriolar diameters returned to baseline, 30% of total blood volumes were removed during a 25 min period. Ten minutes after hemorrhage, rats were treated with a single intravenous(IV) injection of an analgesic dose of fentanyl or ketamine or a comparable volume of saline. Blood pressure, respiratory rate, and arteriolar responses were recorded throughout the experiment.RESULTSBaseline parameters were not different among groups (Table 1). Topical fentanyl induced vasodilation (17 ± 2%, p < 0.01)but ketamine caused vasoconstriction (−15 ± 4%; p < 0.01). IV ketamine and fentanyl failed to affect blood pressure compensation compared with the control group (Figure A). Neither saline nor ketamine altered respiratory rate. However, IV fentanyl induced a prolonged suppression in respiratory rate (>10 minutes, with a peak inhibition at 57 ± 8% of baseline, Figure B). A persistent and similar arteriolar constriction to hemorrhage was observed in the control and ketamine treated groups. However, this compensatory vasoconstriction was absent in the fentanyl‐treated group, which instead exhibited continuous vasodilation (peak change 42 ± 10% of baseline immediately after injection, p <0.01, Figure C). While no mortality occurred with IV saline or ketamine, fentanyl caused an 18% mortality.CONCLUSIONThese results indicate that ketamine preserves, but fentanyl impairs, respiration and peripheral vasoconstrictor response to hemorrhage, although minor effects on initial compensation of systemic hemodynamics appear to be similar. The study suggests that microcirculatory responses may be more sensitive than systemichemo dynamics to predict outcomes during pain management following hemorrhage.Support or Funding InformationThis study was funded by the US Army Medical and Materiel Command, Clinical and Rehabilitative Medicine Research Program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Age‐related Peripheral Vascular Dysfunction Predicts Cognitive Decline in Healthy Individuals
Authors: Csipo Tamas , Fulop Gabor Aron , Lipecz Agnes , Tarantini Stefano , Hand Rachel , Ngo Bich‐Thy , Dzialendzik Mikita , Balasubramanian Priya , Kiss Tamas , Yabluchanska Valeriya , Csiszar Anna , Ungvari Zoltan , Yabluchanskiy Andriy 
Published: June 2021

BACKGROUNDAge‐related vascular cognitive impairment and dementia (VCID), defined as cognitive decline caused by cerebromicrovascular pathologies, is a major public health issue that affects >10 million individuals aged 65 and older in the US with annual healthcare costs totaling >$100 billion. Aging is a major risk factor for the development of VCID and current strategies for VCID treatment are limited to targeting cardiovascular risk factors such as hypertension, diabetes mellitus, etc. Here, we hypothesized that aging, similarly to other risk factors, affects vasculature uniformly and that age‐related changes in the peripheral circulation can be used as an important tool to predict cognitive decline.METHODSFor our study, we have enrolled 55 healthy 22–92 yo individuals and divided them into two groups of young (<45 yo) and aged (>65 yo). Peripheral macrovascular and microvascular endothelial function was measured using a standard flow‐mediated dilation (FMD) and Laser Speckle Contrast Imaging tests (LSCI) in response to increased flow‐mediated shear stress after a 5‐min of blood flow restriction with arterial cuff. Pulse Wave Analysis was used to evaluate the augmentation index (AIx) as a measure of arterial stiffness. A principal component analysis (PCA) approach was used to create a vascular health index (VHI) that included all vascular measurements for each participant. Cognitive function including domain of learning, memory and executive function was measured via a selection of tests from the Cambridge Cognition CANTAB cognitive panel. A PCA approach was used to generate a cognitive impairment index for each participant.RESULTSSubjects from the aged group showed significantly impaired macrovascular endothelial function (FMD, 5.4±0.7% vs. 8.5±0.6% in young, p<0.01) and increased arterial stiffness compared to young (AIx 28.9±1.7% vs 4.5±2.6% in young, p<0.01). Microvascular endothelial function showed significantly lower skin perfusion in aged subjects (2.8±0.1% vs 3.4±0.1% in young, p=0.03) that correlated with FMD measurements (r=0.34, p=0.014), and significantly lower reperfusion rate in aged individuals (25.8±2.2PU/s vs 35.1±2.7 PU/s in young, p=0.01). PCA‐generated Vascular Health Index (VHI) showed a significant negative correlation with age (r=−0.55, p<0.01). VHI correlated with the Cognitive Impairment Index (r=−0.44, p<0.01).CONCLUSIONOur study demonstrates that deterioration of peripheral macro‐ and microvascular endothelial function is associated with and can predict VCID in healthy aged individuals.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Kidney hyperfusion upregulates major histocompatibility complex expression in glomerular endothelial cells through c‐Jun N‐terminal kinase
Authors: Shi Yi , Zhu Dong , Tang Qunye , Meng Mei , Liu Wenjie , Zhu Tongyu , Zhang Yi 
Published: June 2021

ObjectivesThe endothelium is the first line of defense while contacting with the immune system. The present study was investigated roles of antigen representing in glomerular endothelial cells.MethodsC57/BL6 mice were randomly grouped into sham‐operated (2K) and 5/6 nephrectomy groups (5/6Nx). After whole body irradiation, mice were received splenic lymphocytes from either C57/BL6 or Balb/c mice. Human glomerular endothelial cells were cultured in vitro. Blood and renal cortex, and glomeruli were collected for measurement of kidney function, Western blotting, fluorescence‐activated cell sorting and enzyme‐linked immunosorbent assays.ResultsFour weeks after nephrectomy 5/6Nx mice had a normal renal function, but a significantly higher level of renal blood flow, compared with 2K groups, indicating that mice in 5/6Nx have hyper‐perfusion in the kidney. Both mRNA and protein expressions of major histocompatibility complex (MHC) II, CD80, CD86, and interferon γ were upregulated in glomerular endothelial cells of the 5/6Nx mice. Mice injected with lymphocytes from Balb/c mice, but not C57/BL6, had significantly higher levels of serum creatinine, confirming that kidney hyper‐perfusion initiate the immune reaction and the allograft lymphocytes transplant accelerates renal dysfunction. In cultured glomerular endothelial cells, interferon γ significantly upregulated protein expression of MHC II and MHC class I chain‐related genes A (MICA), but not MHC I. Interferon γ also increased transcription factor CIITA protein expression, as well as phosphorylation JNK. JNK inhibitor, SP600125 or JNK peptide, reduced protein expressions of CIITA, MHC II and MICA in cultured glomerular endothelial cells. In the 5/6Nx mice SP600125 or JNK peptide, reduced MHC II expression, but not CD80 or CD86 in the 5/6Nx mice, suggesting that JNK signalling plays a role in the regulation of MHC II protein.ConclusionIn the present study, nephrectomy induces hemodynamic changes in the kidney, leading to increases in major histocompatibility complex protein expression in glomerular endothelial cells. Inhibition of JNK signalling reduces MHC expression in glomerular endothelial cells in vitro and in vivo.Support or Funding InformationThis work was supported by the National Nature Science Foundation of China (No 81573418) and ZSYXRC‐014This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Resting Coronary Blood Flow Velocity by Transthoracic Coronary Echocardiography is Higher in Patients with Cardiovascular Diseases Compared with the Healthy Adults
Authors: Gao Zhaohui , Blaha Cheryl , Cauffman Aimee , Sinoway Lawrence I. 
Published: June 2021

Transthoracic Coronary Echocardiography (TCE), defined as blood velocity detection mainly in the left anterior descending artery (LAD) by noninvasive Doppler echocardiography, has been employed to measure coronary blood flow velocity and coronary flow reserve in research labs and in clinical settings. Most prior studies focused on the coronary flow reserve data, and normal values for resting coronary artery flow velocity have rarely been reported. The purpose of this study was to examine resting coronary blood flow velocity in healthy subjects and patients with cardiovascular disease. We retrospectively collected resting coronary blood flow velocity data by TCE from 69 healthy subjects (42 M, 27 F, 60 ± 8 yrs) and 37 patients (27 M, 10 F, 63 ± 10 yrs) with various cardiovascular diseases (14 peripheral arterial disease, 5 Pre‐TAVR, 8 hypertrophy cardiomyopathy, 10 CABG). The patient group had higher systolic blood pressure (135 ± 18 vs. 120±14 mmHg, P value <0.001), mean blood pressure (94 ± 11 vs. 89 ±10 mmHg, P value <0.05), and Rate‐Pressure Product (RPP, an index of myocardial oxygen demand) (8617 ± 1702 vs. 7249 ± 1453. P value < 0.001). Resting coronary blood flow velocities early (CBV1) and late (CBV2) in diastole were significantly higher in the patient group (CBV1: 27.6±8.6 vs. 19.0 ± 4.9 cm/s, P value < 0.001; CBV2: 17.6 ± 5.5 vs. 13.4 ± 3.2 cm/s, P value <0.001). After controlling for oxygen consumption (CBV/RPP), resting coronary blood flow velocity during the early diastolic period was still significantly higher in patients than in the healthy group (Adjusted CBV1: 3.3 ± 1.4 vs. 2.7 ± 0.8 au, P value < 0.001). There was no significant difference in adjusted coronary blood flow velocity during the late diastolic period (Patient group vs. healthy group, 2.1 ± 0.8 vs.1.9 ± 0.5 au, P value = 0.105). Further studies are needed to explore the clinical implication and importance of higher resting coronary blood flow velocity data by TCE in patients.Support or Funding InformationSupported by National Institutes of Health Grants P01 HL134609 (Sinoway), and UL1 TR002014 (Sinoway).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of P62 Protein in Acute Oxidative Stress‐induced Ventricular Arrhythmias
Authors: Hwang Hyun Seok , Koh Yeojung , Rodriguez Jose , Salazar Gloria 
Published: June 2021

IntroductionChronic ischemia depletes myocardial cells of intracellular defenses from excessive oxidative stress often leads to ventricular arrhythmias. Recently, we reported that autophagy adapter protein, p62 modulate the SR Ca handling in myocytes under chronic myocardial injury. Interestingly, oxidant‐induced beta‐adrenergic signaling involved, it is little known how p62 protein contributes to oxidative stress‐related ventricular arrhythmias in the hearts.PurposeTo investigate the role of p62 protein on acute ischemia‐induced arrhythmogenesis in the intact heart.MethodsIsolated heart from wild‐type (WT) and p62 knockout (KO) mice (n=8 per group) were used at 10–12 weeks of age. Global ischemia protocol applied in isolated heart preparation. Electrocardiography (ECG) recorded during 15 min steady‐state, 30 min ischemia, and 60 min reperfusion to detect heart rate and arrhythmias (premature ventricular contractions; PVCs). At the end of the experiment, ventricles harvested to measure the expression level of proteins, p62, LC3‐I/LC3‐II, and oxi‐CaMII.ResultsThe heart rate (sinus rate) at baseline was not different between the groups. After 30 min ischemia, sinus rate tends to decrease in only p62 KO hearts during the reperfusion. The incidence of arrhythmias significantly attenuated in the p62 KO heart compared to WT heart during the first 15 min of reperfusion (Premature ventricular contraction, PVC/min; WT, 2.71±1.16* vs. 0.26±0.10,* <0.05 vs. WT, Fig.). The deletion of the p62 gene has a beneficial effect on acute oxidative stress‐induced ventricular arrhythmias in the intact hearts.DiscussionOur results suggest that p62 protein involve the oxidative stress‐induced arrhythmogenesis in the hearts, and it may be associated with the intrinsic beta‐adrenergic mechanism.Support or Funding InformationFlorida State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Mapping neutrophil polarization over the myocardial infarction time continuum
Authors: Daseke M John , Valerio Fritz , Lindsey Merry 
Published: June 2021

In response to myocardial infarction (MI), neutrophils are early responders that initiate the inflammatory reaction. However, whether they have other roles in cardiac wound healing has not been explored. We hypothesized that neutrophils may undergo polarization state changes over the MI time course. C57BL/6J male mice (3–6 months old) were subjected to permanent coronary artery ligation to induce MI, and neutrophils were isolated from the infarct region at days, 1, 3, 5, and 7 after MI. Day 0 served as negative no MI controls. Aptamer proteomics was performed on n=10–12 biological replicates for each time, and a total of 123 proteins passed quality control and were assessed. Day 1 MI neutrophils exhibited upregulation of cytokine signaling pathways (IL‐16), extracellular matrix (ECM) degradation (MMP‐8 and MMP‐9), and leukocyte recruitment (calgranulin B). Day 3 MI neutrophils exhibited a similar phenotype, with an increase in ECM reorganization and fibrinolysis (activin A, cathepsin D, and fibrinogen). At MI days 5 and 7, neutrophils displayed a more pronounced shift to ECM reorganization indicated by the continued increase in proteins directly involved in fibrotic pathways (fibrinogen, fibronectin, galectin‐3, and vitronectin). Our results indicate neutrophils show distinct protein expression profiles over the first week of MI. This is the first report to detail the changes in the neutrophil proteome over the first week of MI.Support or Funding InformationNIH GM104357, GM114833, GM115428, HL051971, HL075360, HL129823, and VA 5I01BX000505This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Rosa laevigata Michx‐induced improvement of vascular dysfunction through PI3K/AKT‐mediated NO‐cGMP pathway in endothelial cells and 2K1C hypertensive rat
Authors: Kim Hye Yoom , Ahn You Mee , Hong Mi Hyeon Hong , Yoon Jung Joo , Lee Yun Jung , Kang Dae Gill , Lee Ho Sub 
Published: June 2021

Rosa laevigata Michx has been used to treat chronic cough, arterial sclerosis, menstrual irregularities, and urinary incontinence. The purpose of the present study was to investigate the underlying cellular mechanisms of the nitric oxide (NO)‐mediated property of the aqueous extract of Rosa Laevigata Michaux (ARL). The roles of the NO signaling in the ARL‐induced effects were tested in HUVECs and aortic ring. HUVEC treated with ARL produced higher amount of NO compared to control. ARL increased in the expression and phosphorylation levels of eNOS and Akt in HUVECs, which were attenuated by L‐NAME, a NOS inhibitor, and wortmannin, a PI3K inhibitor. In addition, ARL‐induced dose‐dependent relaxation of phenylephrine‐precontracted aorta was abolished by removal of functional endothelium. Pretreatment with NO‐cGMP inhibited the ARL‐induced vasorelaxation. In addition, an upstream signaling molecule of eNOS, attenuated the ARL‐induced vasorelaxation. Incubation of endothelium‐intact aortic rings with ARL increased the production of cGMP, however, which were attenuated by L‐NAME and ODQ. Two‐kidney‐one‐clip (2K1C) hypertensive rats were established to investigate the hypotensive effect of ARL in renovascular hypertension. 2K1C rats were treated with ARL at dose of 100 mg/kg/day orally for 3 weeks. Consequently, ARL significantly lowered blood pressure, and ameliorates vascular relaxation in thoracic aorta. Taken together, the present study suggests that ARL ameliorates vascular dysfunction via the regulation of endothelium‐dependent activation of through the PI3K/Akt‐mediated NO‐cGMP signaling.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Effects of Oryeongsan in 2K1C rats through regulation of renin‐angiotensin‐aldosterone system and ANP system
Authors: Ahn You Mee , Kim Hye Yoom , Kim Hyun Ju , Yoon Jung Joo , Lee Yun Jung , Lee Ho Sub , Cho Kyoung Woo , Kang Dae Gill 
Published: June 2021

Oryeongsan (ORS) which was first recorded in SangHanLoon, the classic of traditional Chinese medicine describing treatments of disordered body fluid balance. Renal hypertension is caused by renovascular dysfunction through an activation of renin‐angiotensin‐aldosterone system (RAS). The RAS is one of the most important regulators in maintenance of body fluid homeostasis and in long‐term regulation of blood pressure. The purpose of this study is to identify effects of ORS on regulation of renal function, change of blood pressure and RAS in the two‐kidney one‐clip (2K1C) renal hypertensive rats. Experiments were performed in four experimental groups: sham rats, 100 mg/kg/day ORS in sham rats, 2K1C rats and ORS in 2K1C rats, respectively. After 4 weeks of operation, sham and 2K1C rats were administered with vehicle or ORS for 3 weeks. Urinary volume, urinary excretion of Na+, K+, Cl−, osmolality and creatinine were measured. The 2K1C rats showed significantly higher systolic blood pressure (SBP) compared with sham rats. ORS treatment for 3 weeks markedly decreased the SBP in 2K1C rats. ORS significantly increased urinary volume, urinary excretion of electrolytes, and clearance of creatinine (CCr) in 2K1C rats. ORS significantly suppressed plasma level of PRA, Angiotensin II and aldosterone in 2K1C rats. Also, ORS suppressed the upregulated RAS components in the kidney from 2K1C rats. However, ORS increased plasma level of ANP in 2K1C rats. These findings suggest that ORS may elicit renal and vascular effects via two ways: directly and indirectly through activation of the ANP system and inhibition of the RAS.Support or Funding InformationThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.