bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes In Some Liver Enzymes Activities Of Albino Rats After Prolonged Intake Of Antihypertensives; B‐Blockers And Moduretics
Authors: ANACLETUS FRANCIS C. , ONYEGEME‐OKERENTA BLESSING MINAOPUNYE , ONWUKA ADAORA PATIENCE 
Published: June 2021

Antihypertensive drugs; beta‐blockers with moduretics are the classes of therapeutics used in the management of cardiac arrhythmias, and to protect the heart from a second heart attack after a first heart attack. They play important roles in the treatment of many cardiovascular diseases. This study investigated the possible effect of prolonged use of these beta‐blockers on liver function.Twenty wister rats with average weight of 180g each were carefully examined and grouped into 4 (5 per cage). Group 1 served as the normal control. Group 2 was administered a normal dose of the drug combination (25 mg of the B‐blocker in 50·ml of distilled water and 25 mg of moduretic in 50 ml of distilled water respectively), Group 3 was administered with overdose of the drug combination (50 mg of the B‐blocker in 50 ml of distilled water and 50 mg of moduretic in 50 ml of distilled water). Administration of the drugs was done for four weeks for these two groups. Group 4 was administered a normal dose of the drug combination but for a prolonged period of six weeks. Biochemical markers used for this test to ascertain the integrity of the liver were, Alanine transaminase (ALT), Aspartate transaminase (AST), and Alkaline phosphatase (ALP), were measured. Results obtained after 4 weeks showed a significant increase (p<0.05) in ALT of group 3(28.00±3.60) when compared to the groups 1 (8.66±0.66) and 2(14.66±1.45). ALT activities after 6 weeks showed a significant increase (p<0.05) for group 4 (34.66±2.60) when compared to groups 1 and 2. Similarly ALP results for group 3 after 4 weeks of treatment showed a significant increase (p<0.05) in activities (155.66±12.98) when compared to groups 1 (96.16±12.53) and 2 (93.73±8.44) as well as in group 4 (99.96±10.35) after 6 weeks of treatment. Furthermore, AST activities obtained in group 3 (71.33±2.60) after 4 weeks and group 4 (58.66±4.91) after 6 weeks showed a significant increase (p<0.05) when compared to the groups 1 (37.66±4.97) and 2 (42.33±8.95). The result showed that there was an average change in liver markers in the group treated with B‐blockers in combination with moduretics when taken for a prolonged period as is always prescribed for known hypertensivesSupport or Funding InformationSelf fundingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Reducing Disparities in the Treatment of Hypertension in African Americans Using Computational Modeling
Authors: Clemmer John S. , Pruett W. Andrew , Hester Robert L. 
Published: June 2021

African Americans (AA) develop hypertension (HTN) at an earlier age, have a greater frequency and severity of HTN, and have poorer control of blood pressure (BP) as compared to the white population. The mechanisms responsible for these disparities are unknown. The multifactorial nature of HTN and the similar presentation of its etiologies complicate its treatment. Mathematical modeling provides the ability to analyze complicated interrelated effects across multiple systems. Our current model, HumMod, is a large physiological simulator that is comprised of 14 organ systems, and includes key systems that play an integral role in BP control such as neural, endocrine, circulatory, and renal systems. We have created tools that integrate HumMod to generate virtual populations that are calibrated from clinical data. Thiazide (THZ) diuretics generally reduce BP and improve cardiovascular outcomes in AA. Using de‐identified clinical data from the Genetic Epidemiology Network of Atherosclerosis (GENOA) study, we calibrated virtual populations to normotensive AA or hypertensive AA with or without THZ therapy. The clinical and virtual populations were statistically similar in multiple variables including mean arterial pressure (MAP), glomerular filtration rate (GFR), left ventricular mass index (LVMI), cardiac output, and total peripheral resistance (Figure 1). Interestingly, virtual patients that did not respond to 4 weeks of THZ therapy (ΔMAP = 0±5 mmHg) were associated with greater falls in renal hemodynamics, activation of the renin‐angiotensin system, and decreased plasma atrial natriuretic peptide (ANP) as compared to THZ responders (ΔMAP = −9±3 mmHg) (Figure 2). This suggests that differences in the hormonal response to diuretic therapy may be an important factor that prevents successful HTN treatment in AA. These data are both a proof of concept of established physiology and a tool to test existing and new hypotheses of the mechanisms of nonresponse to varying antihypertensive regimens. These techniques and the potential insights gleaned from these simulations may also have broad implications for improving BP control in other hypertensive populations.Support or Funding InformationSupported by AHA 17POST33661071 and NIH PO1 HL51971This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Roles of Vascular Risk Factors In A Neurological Disease
Authors: Shim Joon W. 
Published: June 2021

AimWe have previously reported that angioneurins such as vascular endothelial growth factor that exert both vasculotrophic and neurotrophic activities can play a diverse role and transform into a pathogenic mediator of post‐hemorrhagic hydrocephalus in young brains. The objective of this study was to better understand the roles of vascular risk factors in the brain with an age‐related neurological condition.MethodsLiteratures reporting a relationship between vascular risk factors such as arterial stiffness and age‐related disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) were surveyed. Elastin gene expression was quantified in the thoracic aorta of male mice with young and old age and of young mice fed with high fat high sucrose (HFHS) diet. Aortic stiffness was assessed in vivo using ultrasound and compared to age‐, diet‐, and gender‐matched mice with constitutive deletion of phospholipase A2 group 6 (PLA2g6). Gene expression analysis was conducted on aortic medial layer RNA and validated by elastic fiber staining. Cell‐specific effect on elastin gene expression and arterial stiffness was further tested in a mouse model with SMC‐specific impairment of PLA2g6.ResultsAn inverse interrelationship between the PD and vascular risk factors including smoking and vascular stiffness were noted. Animal experiments revealed that aging and HFHS‐diet induced arterial stiffening in wild type (WT) animals but not in PLA2g6 knockout mice. The qRT‐PCR revealed that elastin gene expression was significantly elevated regardless of age in PLA2g6 impaired mice. The mRNA expression of Sp1 transcription factor was significantly increased in aged PLA2g6 knockout aorta. Mice with SMC‐specific deletion of PLA2g6 at young age showed significantly reduced arterial stiffness with elevated elastin during HFHS diet.ConclusionThese results demonstrate that a vascular risk factor such as arterial stiffness declines with aging through modulation of age‐induced loss of elastin in arteries of mice with impaired PLA2g6 exhibiting PD symptoms. Molecular targets promoting expressions of vasculoprotective gene such as elastin along the cell‐specific pathway may provide novel therapies for the protection against an increase of vascular risk and the better understanding to the associated age‐related neurodegeneration.Support or Funding InformationJ.W.S is supported by the Fellowship from the Multidisciplinary Postdoctoral Training Program in Cardiovascular Research (NIH 5T32HL007224‐39).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CD70 Modulates the Role of eNOS In Endothelial Cells
Authors: Pandey Arvind K. , Brown Jonathan D. , Harrison David G. , Itani Hana A. 
Published: June 2021

CD70 has traditionally been identified on antigen presenting cells and interacts with CD27 on T cells, promoting proliferation and memory cell formation. We have recently shown that CD70 is important in the formation of effector memory T cells in hypertension. However, the precise cell types that express CD70 and the role of CD70 on non‐immune cells has not been investigated. Here we describe a new role of CD70 in endothelial function. We found that human umbillical vein endothelial cells express CD70 mRNA and that this is increased by > 30 fold by laminar (15 dynes/cm2) compared to oscillatory shear. Studies of mesenteric vascular reactivity showed that CD70−/− mice have markedly impaired endothelium‐dependent vasodilation to acetylcholine compared to WT mice (45± 5 vs 25 ± 4 %) at baseline. In contrast, there were no differences in relaxation responses to sodium nitroprusside. Pre‐incubating vessels with the endothelial nitric oxide synthase (eNOS) inhibitor L‐NAME blocked endothelium‐dependent vasodilatation to acetylcholine in WT mice nearly 75%; in contrast, L‐NAME had no effect on endothelial vessel relaxation in CD70−/− mice. This suggests that vessels of CD70−/− mice lack the capacity to produce nitric oxide (NO). Western blot for the endothelial nitric oxide synthase (eNOS) showed a marked reduction of this enzyme in the aortas of CD70−/− as compared to wild type mice. We found that CD70 and eNOS interact by co‐immunoprecipitation, however this association is abolished by siRNA against CD70. In additional experiments, aortas from CD70−/− did demonstrate expression of both neuronal NOS (nNOS) and inducible NOS (iNOS). In order to assess functional effects of this expression, nNOS NO production was blocked with LVNIO, resulting in further impairment in vasodilation of CD70−/− mesenteric vessels (−logEC50 of 5.4 after treatment, compared to 6.2 before treatment); however blockade of iNOS with 1400 W resulted in apparent recovery of acetylcholine‐induced vasodilation. These data indicate that loss of CD70−/− leads to destabilization of the eNOS protein in endothelial cells resulting in endothelial dysfunction. In the absence of eNOS in CD70−/− vessels, iNOS contributes to endothelial dysfunction, while nNOS has a compensatory role. These studies have identified a new role of the immune co‐stimulatory protein CD70 in modulating endothelial eNOS protein levels and vascular function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Roles of MicroRNAs in Atherosclerosis and Neointimal Lesion Formation under Flow
Authors: Chiu Jeng‐Jiann , Chen Li‐Jing , Lee Ding‐Yu 
Published: June 2021

Atherosclerosis, a vascular pathology responsible for most cardiovascular‐related morbidity and mortality, develops predictably in regions of the arterial tree in which wall shear stresses are generated by complex patterns of blood flow. It has been recognized that hemodynamic characteristics determine the location of lesions and contribute to the pathogenesis of atherosclerosis. The key cells involved in atherogenesis include vascular endothelial cells (ECs) and smooth muscle cells (SMCs). Recent evidence suggests that laminar blood flow in the straight part of the arterial tree and high shear stress modulate cellular signaling and EC function, and protect against atherogenesis. In contrast, disturbed flow in bifurcations of the arterial tree and the associated oscillatory low shear stress enhance leukocyte infiltration of the arterial wall and thus are atherogenic. However, little is known about the effect of disturbed flow on ECs, especially on their interactions with SMCs, whose phenotypic switching is significantly implicated in atherosclerosis and neointimal lesion formation. Our recent studies using microRNA (miR) assay, in vitro EC‐SMC co‐culture flow system, experimental animal models, and human specimens from patients with coronary artery disease (CAD) have identified several miRs to be involved in the formation and progression of atherosclerosis. Among these miRs, miR‐146a and 10a play atheroprotective roles in ECs against atherogenesis induced by disturbed flow. MiR‐451, by targeting Rab5a, inhibits vascular SMC proliferation and inflammation and suppresses injury‐induced neointimal lesion formation. Our findings help the discovery of new target biomarkers and elucidation of functional mechanisms underlying atherosclerosis, thereby facilitating the development of new approaches for therapeutic interventions.Support or Funding InformationThis work was supported by grants from the Ministry of Science and Technology in Taiwan (grant numbers: MOST‐106‐2633‐B‐009‐001, 105‐2321‐B‐400‐007, 106‐3114‐Y‐043‐021)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Effect of Dietary Nitrate on Vascular Function in Chronic Kidney Disease
Authors: Ramick Meghan G. , Kirkman Danielle L. , Stock Joseph M. , Muth Bryce J. , Chirinos Julio A. , Edwards David G. 
Published: June 2021

PURPOSEThe purpose of this study was to test the hypothesis that an acute dose of 12.6 mmol dietary nitrate in the form of concentrated beetroot juice (BRJ) would improve measures of microvascular and conduit artery endothelial function in patients with moderate to severe chronic kidney disease (CKD).METHODSFifteen adults with moderate to severe CKD participated in this double blind, randomized, crossover study (61±4 yrs; 11 males; eGFR 49.2±3.4 ml•min−1•1.73 m2). Participants reported to the laboratory and baseline blood pressure (BP) was measured and a baseline blood sample obtained for determination of NO metabolites (NOm; Nitrate, nitrite, s‐nitrosothiols and metal bound NO). Participants were then randomized to ingest 12.6 mmol of BRJ or a nitrate depleted placebo (PLA). Vascular testing began 2.5 hours post beverage ingestion. A second blood sample was obtained and post‐ingestion BP was recorded. Microvascular function was assessed via the cutaneous response to local heating measured by laser Doppler flowmetry coupled with microdialysis, and conduit artery function was assessed via brachial artery flow‐mediated dilation (FMD). Arterial stiffness (via carotid‐femoral pulse wave velocity, PWV) was also measured. The entire protocol was repeated a minimum of 7 days later in the other condition.RESULTSPlasma NOm was not different between conditions at baseline but was significantly increased 2.5 hours post BRJ ingestion compared to pre‐ingestion values, as well as compared to post PLA values (PREPLA 53.0±11.6 POSTPLA 33.2±9.9 mM; PREBRJ 57.3±21.4 vs POSTBRJ1068.0±106.6 mM). Mean arterial pressure (MAP) was not different between conditions at baseline or 2.5 hours post, however the change in MAP from pre‐ingestion baseline to 2.5 hours post ingestion was significantly different between conditions (ΔMAPPLA 2.0±2.1 vs ΔMAPBRJ −3.2±2.6 mmHg, p>0.05). The plateau phase of the cutaneous response to local heating was significantly greater in the BRJ condition compared to PLA (PLA 83.4±2.2 vs BRJ 88.8±1.7%CVCmax; p<0.05). The NOS mediated contribution to the plateau phase as assessed via L‐NAME infusion was not different between conditions. We did not observe any improvements in FMD or PWV.CONCLUSIONAn acute dose of 12.6 mmol dietary nitrate significantly improves microvascular function in patients with moderate to severe CKD.Support or Funding InformationThis research was supported by an ACSM Foundation Research Grant from the American College of Sports Medicine Foundation and NIH grant HL113514.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
EVALUATION OF SARCOPENIA IN PATIENTS WITH ACUTE KIDNEY INJURY: USE OF SERUM BIOMARKERS
Authors: Lanzoni Luís Gustavo , Morales Armando , Silveira Cylmara Gargalak Aziz , Grabulosa Caren Cristina , Tinucci Taís , Moysés Rosa Maria Affonso , Quinto Beata Marie Redublo , Batista Marcelo Costa , Dalboni Maria Aparecida 
Published: June 2021

IntroductionSarcopenia is a syndrome characterized by progressive loss of skeletal muscle mass, decreased strength, decreased physical performance, increased risk of falls, fractures, hospitalization, and mortality. In patients with chronic renal disease on dialysis (CKD) approximately 40% present sarcopenia due to the effect of toxic substances that are not excreted and induce activation of the inflammatory response that contributes to muscle catabolism, mitochondrial alterations, decrease of satellite cells, changes hormones and loss of neuromuscular junctions. Sarcopenia is well documented in patients with CKD, where the diagnosis is made by measuring the skeletal muscle index, measuring the strength of the wrist and low speed in walking.However, in patients with acute kidney injury (AKI) who abruptly lose kidney function; sarcopenia has not yet been investigated. In addition, because these are hospitalized in intensive care units, the classic characterization of sarcopenia by measuring skeletal muscle mass is not possible; requiring the use of serum biomarkers that represent the loss of muscle mass.ObjectiveObjective of this study was to investigate sarcopenia through serum markers of muscle mass loss in AKI patients.Material and MethodsWe included 77 severe patients without AKI and 83 severe AKI patients all admitted to the Intensive Care Unit. Patients with AKI were characterized by AKIN criteria that used a 0.3 mg/dL increase in serum creatinine within seven days of admission in the hospital. Serum markers of sarcopenia: growth factor like insulin‐1 (IGF‐1), myostatin, interleukin‐6 (IL‐6), tumor necrosis factor alpha (TNF‐α) and interleukin‐15 (IL‐15) were studied by enzyme‐linked immunosorbent assay (ELISA). Results are expressed as median. Mann‐Whitney test was used to analyze the groups.ResultsAll AKI patients presented serum creatinine> 3.1 mg/dL (reference value 0.8 – 1.3 mg/dL). We observed increased serum IL‐6 (pg/mL) levels [AKI 21 (11 – 32) vs. No‐AKI 12 (7–19); p <0.001], TNF‐α (pg/mL) [AKI 8.2 (6.7 – 10.5) vs. No‐AKI 7.0 (6.2–7.9); p <0.001], IL‐10 (pg/mL) [AKI 1.1 (0.8 – 1.6) vs. No‐AKI 0.8 (0.7 – 1.0); p <0.001], and IL‐15 (pg/mL) [AKI 5.8 (3.3 – 7.7) vs. No‐AKI 4.5 (2.8 – 6.1); p = 0.04] and we did not observe differences in IGF‐1 (ng/mL) [AKI 0.3 (0.1 – 0.5) vs. No‐AKI 0.3 (0.2 – 0.4); p = 0.53] and myostatin (ng/mL) [AKI 33 (19 – 57) vs. No‐AKI 37 (20–59); p = 0.30].ConclusionAKI patients presented higher inflammation characterized by increased serum levels of IL‐6, TNF‐α and IL‐15, which may contribute to sarcopenia. However, myostatin and IGF‐1 did not behave as a marker of muscle loss in this population studied.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Cdc42 Activation by Endothelin Regulates Neural Crest Cell Migration in the Cardiac Outflow Tract
Authors: Ruest L. Bruno , Fritz Katrina R. , Jansen Erik P. 
Published: June 2021

Congenital cardiovascular malformations are the most common birth defects affecting children. Several of these defects occur in structures developing from neural crest cells (NCC) that migrate ventrally to populate the pharyngeal arches. Cardiac NCCs (CNCC) participate in the asymmetric remodeling of the pharyngeal arch arteries (PAA) into the great vessels and the septation of the cardiac outflow tract (COFT) into the pulmonary and aortic outflows. One of the key signaling pathways regulating CNCC development involves the Endothelin‐A receptor (Ednra). The absence of Ednra signaling in the mouse causes severe cardiovascular defects, including patent ductus arteriosus, coarctation of the aorta, persistent truncus arteriosus and ventricular septal defects. However, the exact function of Ednra signaling in CNCCs is unknown.CNCC fate mapping in the Ednra mouse revealed that the migration of these cells is aberrant in the COFT of the mutant embryos, but not in the pharyngeal arches. This premature arrest of CNCC migration appeared to be independent of CNCC proliferation and apoptosis changes. These results suggest that Ednra has a patterning function in the pharyngeal arches and controls CNCC migration in the COFT. Based on these results, we tested whether CNCC migration was arrested prematurely because CNCCs fail to activate specific cell migratory mechanisms by looking at migratory markers of the Rho family of GTPases. In the mutant embryos, Cdc42 fails to localize at the migratory front of the CNCCs migrating in the COFT. Cultured E9.25 whole embryos treated with the Cdc42 inhibitor ML141 recapitulated the phenotype. To confirm that Ednra and Cdc42 were acting in the same pathway, primary NCC from the cardiac area and mandibular pharyngeal arch were isolated for culture and treated with the Ednra ligand Edn1, ML141 and Ednra antagonist TBC3214. Western blot analysis revealed that Edn1 stimulated the phosphorylation of the Cdc42 downstream target ACK only in CNCCs and the addition of either inhibitor prevented ACK phosphorylation. Erk1/2 phosphorylation was observed in the mandibular NCCs upon Edn1 treatment but this was not prevented by the addition of the Cdc42 inhibitor. Wound healing scratch assay showed that the addition of Edn1 stimulated CNCC migration, which was repressed by the addition of either the Ednra or Cdc42 inhibitor. However, no such stimulation or inhibition was observed with the mandibular NCCs.In conclusion, these results demonstrate that endothelin signaling controls the migration of NCCs in the COFT via the specific activation of Cdc42 and this pathway is not necessary for the migration of NCC in the pharyngeal arches and the rearrangement of the pharyngeal arch arteries.Support or Funding InformationAmerican Heart Association 11BGIA 5670010NIH T32 DE018380Baylor Oral Health FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.