bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlates of ambulatory blood pressure in healthy young women: nutrition, physical activity and stress
Authors: Bedford Jennifer L. , Barr Susan I. 
Published: June 2021

Young adult blood pressure predicts cardiovascular risk in later life. This study explored relationships between ambulatory blood pressure (ABP) and dietary intake, physical activity and stress in 120 healthy, non‐obese, 19‐35 yr old women. Participants completed a food frequency questionnaire, the Baecke physical activity questionnaire and the Perceived Stress Scale (PSS). Height, weight and 24‐hr urinary free cortisol (UFC) were measured. An ABP monitor was worn for 12 hr with measurements every 30 min to determine average systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP) and pulse pressure (PP). Height, weight and physical activity correlated positively with PP. Age correlated negatively with PP and positively with DBP. Partial correlations, controlling for age, height, weight, physical activity and energy, revealed few significant associations (p<0.05) between nutrients and ABP: SBP correlated positively with saturated fat; SBP and MAP correlated negatively with thiamin; and DBP correlated positively with sodium. Several nutrients correlated negatively with PP: protein as % of energy, dietary folate equivalents, sodium, and selenium. SBP, DBP and MAP were positively associated with UFC (r=0.26, 0.24 & 0.26, p<0.01). ABP was not related to PSS score, though UFC and PSS score correlated positively. In this study, relationships between ABP and dietary intake or physical activity were weak, and most were with PP, an indirect index of arterial stiffness, rather than with SBP, DBP or MAP. In contrast, stress (as reflected by UFC) appeared to be a stronger correlate of ABP in these young women. Project funded by CIHR MOP 79563.Grant Funding SourceCanadian Insitutes of Health Research
Barley protein supplementation and oxidative damage
Authors: Wong Julia M W , Srichaikul Kristie , Fozdar Nishant , Kendall Cyril W C , Jenkins David J A 
Published: June 2021

ObjectiveTo assess the effect of vegetable protein as high protein barley flour, baked into bread, on risk factors for heart disease (i.e. serum lipids and markers of oxidative damage).MethodIn a randomized controlled crossover design, 23 hypercholesterolemic adults (16F, 7M; 57±7y; LDL‐C, 3.90±0.21mmol/L) completed two 4‐week treatments of bread supplementation containing either 30g/d (per 2000 kcal diet) of barley protein (treatment) or dairy protein (calcium caseinate placebo). Outcomes included serum lipids and markers of oxidative damage, measured as serum protein thiols, and MDA and conjugated dienes in the LDL fraction.ResultsAt week 4, supplementation with barley protein did not provide evidence of improved LDL‐C and TC:HDL‐C, expressed as the difference from baseline (‐0.05±0.12 mmol/L, P=0.685 and 0.19±0.15 mmol/L, P=0.216, respectively) compared to control (‐0.02±0.12 mmol/L, P=0.858 and 0.19±0.11 mmol/L, P=0.094, respectively). No effect was seen on serum protein thiols, as an overall marker of oxidative status. In addition, neither MDA nor conjugated dienes in the LDL fraction, as markers of oxidized LDL, were affected differently by barley compared to dairy protein.ConclusionBarley protein appears similar to low fat dairy protein in its effect on blood lipids and markers of oxidative damage.Research Support: NSERC, Loblaw Companies LimitedGrant Funding SourceCanadian Institutes of Health Research
Nitric oxide inhibition of chronic Hcy‐induced endothelial cell (EC) activation is cGMP‐independent
Authors: Graham Anne Margaret , Alkhoury Kenan , Naseem Khalid , Parkin Susan Mary 
Published: June 2021

Hyperhomocysteinemia (hHcy) upregulates expression of cell adhesion molecules (CAM) on EC which recruits leukocytes and initiates atherosclerotic lesion development. Nitric oxide (NO) is anti‐adhesive for leukocytes.Objectiveto study effects of exogenous NO on hHcy CAM expression in human umbilical vein endothelial cells (HUVEC) and recruitment of leukocytes under flow.HUVEC were cultured for 5‐9 days in medium containing 1mM Hcy or Cysteine (negative control). Some Hcy‐stimulated cells were treated with NO donor (S‐nitrosoglutathione: GSNO: 20µM, 10min) in absence of presence of a cGMP inhibitor (ODQ 40µM, 30min). Confluent cells were subjected to flowing neutrophils (1x106cells/ml) at 1.1dynes. Tethered, rolled, fixed and transmigrated neutrophils on HUVEC were counted. Immunofluorescence antibodies against ICAM‐1, E‐selectin and P‐selectin quantified adhesion molecule expression.Hcy induced expression of ICAM‐1, E‐selectin and P‐selectin (p<0.05) and significantly increased interactions between neutrophils and HUVEC while cysteine had no effect. When Hcy‐treated HUVEC were exposed to GSNO with or without ODQ, numbers of all interactions decreased dramatically but significantly decreased only P‐selectin expression (p<0.05).NO inhibits HUVEC: leukocyte interaction through inhibiting the expression of P‐selectin in a cGMP‐independent manner.Funding: HRUK, ORSAS
Role of cellular senescence in the age‐associated risk of venous thrombosis
Authors: Cardenas Jessica Caroline , Krishnamurthy Janakiraman , Sharpless Norman , Whinna Herbert , Church Frank 
Published: June 2021

During normal aging, expression of the tumor‐suppressor gene, p16ink4a, results in cellular senescence in many tissues, including the vasculature. We hypothesize that p16ink4a‐mediated cellular senescence is associated with impaired hemostasis and contributes to a prothrombotic phenotype. In this study, we have used in vivo murine models of vascular injury to examine the role of p16ink4a and cellular senescence in venous thrombosis. Transgenic mice over‐expressing p16ink4a were developed and real‐time PCR data show a 6.5 fold increase in expression of p16ink4a in the saphenous vein/artery bundle. When challenged with an acute ferric chloride injury to the saphenous vein, the p16ink4a transgenic mice have a significantly shorter occlusion time when compared to wild‐type controls. Wild‐type mice show an average occlusion time of 20 minutes versus 13.5 minutes in the p16ink4a transgenic mice. Additional studies have shown that p16ink4a does not alter blood cell populations or venous flow velocity. Currently, we are examining the role of cellular senescence in the response to injury over time. Our results suggest the p16ink4a transgenic mice have a delayed response to injury and are more sensitive to damage induced by ferric chloride. Our studies with the transgenic p16ink4a mice are the beginning to our understanding the role of cellular senescence in the risk of venous thrombosis.NIH support 1R21AG031068‐01.
Curcumin protects against glucose‐induced endothelial dysfunction through HO‐1 and GC pathway
Authors: Fang Xiao‐dong , Yang Fan , Zhu Li , Shen Yue‐liang , Chen Ying‐ying 
Published: June 2021

AimTo investigate the effect and mechanism of curcumin on high glucose induced injury in blood vessels.MethodsThe thoracic aortic rings with or without endothelium from male SD rats were mounted in an organ bath. Isometric contraction of aortic rings was measured. Heme oxygenase (HO) activity was also evaluated.Results(1)After incubation with 44 mmol/L of high glucose for 2 h, the vascular relaxation response to acetylcholine (Ach) decreased in an endothelium‐dependent manner; (2)Coincubation with curcumin (10−13~10−11 mol/L) and high glucose, the high glucose‐induced vasodilation dysfunction was inhibited in a dose‐dependent manner; (3) Curcumin increased the HO activity of thoracic aorta. ZnPPIX (an inhibitor of heme oxygenase‐1) offset the protective effect of curcumin. ; (4) A non‐selective guanylate cyclase (GC) inhibitor methylene blue also completely abolished the protective effect of curcumin.ConclusionCurcumin could alleviate the high glucose‐induced acute endothelium‐dependent vasorelexation dysfunction in rat aortic rings. HO‐1 and GC were proposed as a mechanism to account for the protection of vascular responses by curcumin.
Overexpression of VEGF165b in mouse ovary results in reduced litter size
Authors: Qiu Yan , Murphy David , Harper Steven J. , Bates David O. 
Published: June 2021

Physiological angiogenesis occurs in the ovary, and facilitates oxygen, nutrient, and hormone substrate delivery and transfer of synthesized hormones to targeted cells. VEGF plays a key role in the regulation of ovarian follicle development and corpus luteum formation and maintenance.VEGF is differentially spliced in the terminal exon to form two families of proteins, termed VEGFxxx and VEGFxxxb, where xxx denotes the amino acid number. VEGF165b inhibits VEGF165 induced endothelial cell proliferation, migration, vasodilatation and in vivo angiogenesis,To identify the biological function of VEGF165b in the ovary, nine female transgenic mice (TG) overexpressing VEGF165b under the control of the MMTV promoter and 10 wild type (WT) female littermates were mated with WT C57Bl6 mice. RT‐PCR indicated strong expression of VEGF165b in ovaries of TG females. TG mothers produced litters of half the size of WT dams (3.3±0.4 vs. 5.8±0.7 pups/litter), or TG males (6.1±0.7 pups/litter). There was no developmental defect identified in either the WT or TG pups from TG mothers suggesting subfertility due to defects in the female reproductive system. We have therefore shown that over‐expression of VEGF165b reduces fertility, possibly by its anti‐angiogenic actions on follicular development. This project is supported by the Wellcome Trust and British Heart Foundation.
Acute vascular changes in renal arterial anatomy after cryosurgery
Authors: Spaan Jos , Lagerverld Brunolf , van Horssen Pepijn , van den Wijngaard Jeroen , de la Rosette Jean , Wijkstra Hessel 
Published: June 2021

IntroductionCryosurgery is gaining importance as an optional curative or palliative treatment technique for urological cancers. The aim is to indicate which part of the microcirculation is acutely destroyed by this technique.MethodsIn 6 anesthetized pigs kidney cryoablation was applied for 20 minutes using a triple needle probe configuration (Cryoneedle TM). The kidneys where allowed to thaw in situ and then excised., its main artery was flushed with saline and filled with a fluorescence dyed elastomere. The kidney was, frozen and processed in an imaging cryomicrotome. After each slice the fluorescence in the cutting plane was measured applying a 2000 by 2000 pixel digital camera. 3 D image processing revealed information about arterial structure down to 20 μm vessels. As a statistical measure the summed length, Ld of all segments having a diameter, d, were summed for regions of interest, ROI.ResultsThe ablated zones were clearly noticeable in the white light and 3‐D fluorescent images. The histograms of Ld versus d as well as dPeak (d where Ld is maximal) where independent of the selection of non‐ablated ROI. For ablated areas dPeak shifted to larger diameters by 70 microns and Ld at dPeak without ablation reduced by a factor of 10.ConclusionAfter cryoablation, acute injury of the renal arterial vessels induced destruction of the vessels smaller than 200 μm leaving the structure of larger vessels intact.
Sickle Cell transgenic mice demonstrate a pro‐thrombogenic phenotype
Authors: Gavins Felicity n.e. , Russell Janice , Granger D Neil 
Published: June 2021

In this study we investigated the mechanisms involved in thrombus formation in sickle cell disease (SCD) because SCD patients are more susceptible to thrombotic events, with unknown reason.Thrombosis was induced using the light/dye method in cerebral venules and arterioles of wild‐type (WT:C57Bl/6), sickle cell transgenic (SCD; βs) and WT/βs chimeric (positive control) mice (1). Flow cessation time was recorded.Thrombus formation was reduced by 50% in SCD mice vs. WT in venules and arterioles, but not observed in chimeric mice.The clinical implication of anti‐coagulant therapy was investigated, using Hirudin and anti‐thrombin III (AT3) inhibitor. Hirudin increased thrombus formation in SCD mice, but only in WT venules, suggesting a possible heightened sensitivity in SCD microvasculature. The AT3 inhibitor increased flow cessation in all vessels of WT and SCD mice, implicating the importance of all coagulation pathways.This study further supports the growing evidence for a pro‐inflammatory and pro‐thrombogenic microcirculation in SCD mice, in particular the notion that SCD promotes thrombus formation. Understanding the susceptibility and pathways involved in thrombogenic situations that occur in SCD, it may lead to the identification of potential therapeutic targets in this painful and life‐threatening disease.Supported by the BBSRC1. Wood, K. et al. AJPHCP. 2004.
Enhanced Carbachol‐Mediated Relaxation in Aorta of Mice Lacking the Potassium Channel TWIK‐2
Authors: Lloyd Eric Edward , Namiranian Khodadad , Marrelli Sean P , Bryan Robert M 
Published: June 2021

TWIK‐2, a member of the Two‐Pore Domain K channel family, is highly expressed in the vascular system, however the function is unknown. We hypothesized that TWIK‐2 is involved with regulating vascular tone in arteries and tested this hypothesis on animals lacking TWIK‐2 (KO). Body composition analyses and blood pressures were similar in the KO and wild type (WT) mice. Isolated arteries were evaluated by wire myography. The tension in response to 60 mM KCl was enhanced in the TWIK‐2 KO. However, constrictor responses to phenylephrine and U46619, a thromboxane A2 mimetic, were similar. Relaxation to carbachol, an acetylcholine analog, was measured after precontraction with phenylephrine (0.5 μM). Arteries from KO animals showed that dose dependent relaxations to carbachol were enhanced by 37% (n=5, p<0.01). The NO‐synthase inhibitor, L‐NAME (100 μM), abolished the relaxations to carbachol in both strains. In summary, our data indicates that TWIK‐2 does have a role in regulating arterial tone. Additional studies are ongoing to determine the specific mechanism of TWIK‐2 in regulating vascular tone.This work was supported by research grants R01 NS 46666 and NS 038660.
Correlation between acute stroke and microalbuminuria. Potential role of underlying systemic microvascular endothelial disease
Authors: Toth Peter , Koller Akos , Marko Lajos , Halmai Richard , Bosnyak Edit , Szapary Laszlo , Komoly Samuel , Nagy Judit , Wittmann Istvan 
Published: June 2021

We hypothesized that ischemic stroke is a manifestation of a systemic microvascular endothelial disease, which is thought to be characterized by microalbuminuria (albumin/creatinine: male patients: 2.5‐25; female patients: 3.5‐35 mg/mmol). Thus in patients with acute ischemic stroke (n=100) HPLC was used to measure urinary albumin/creatinine and glomerular filtration rate was estimated (eGFR) by the MDRD formula to characterize kidney function. To assess the severity of stroke the Scandinavian Stroke Scale (SSS) and the National Institute of Health Stroke Scale (NIHS) were used. We have found that 54.1% of stroke patients with normal kidney function (eGFR above 90 ml/min/1,73m2) had microalbuminuria. In addition, 69% of stroke patients with microalbuminuria had decreased kidney function, as well (eGFR below 90 ml/min/1,73m2). The severity of microalbuminuria correlated significantly (p<0,01) with the severity of stroke (SSS: NM: r = ‐0,38; HPLC: r = ‐0,35; and NIHS: NM: r = 0,24; HPLC: r = 0,24). We suggest that both ischemic stroke and microalbuminuria are likely a consequence of a systemic vascular endothelial disease and thus it seems to be important to assess microalbuminuria and kidney function in all stroke patients.Grants: Hungarian Sci. Res. Funds/OTKA T48376, K71591, F68638; Health Sci. Council/ETT 364/2006, Hungarian Neuroimaging Foundation, Am. Heart Assoc. Founders Aff. 0855910D, USA
NFATc3 is required for chronic hypoxia‐induced pulmonary hypertension: role of BKα and β subunits
Authors: Bierer Ryann , de Frutos Sergio , Nitta Carlos H , Resta Thomas C , Friedman Jessica , Gonzalez Bosc Laura 
Published: June 2021

Chronic hypoxia (CH)‐induced pulmonary arterial remodeling and right ventricular (RV) hypertrophy require NFATc3 activation. Hence, we hypothesized that NFATc3 is also required for CH‐induced pulmonary hypertension. Mean RV pressure (MRVP mmHg) was measured in anesthetized wild type (WT) mice treated with cyclosporine A (CsA, 25 mg/Kg/day, NFAT inhibitor) or vehicle (V)‐containing food, and in NFATc3 heterozygote (HET) and knockout (KO) mice exposed to normoxia (N) or CH (380 mmHg; 21 days). CsA significantly attenuated CH‐induced increases in MRVP.CH increased MRVP in WT and HET but not in KO mice (NWT: 11.8±2.3; NHET: 10.4±1.8; NKO: 15.5±3.6; CHWT: 20.0±4.4*; CHHET: 16.1±4.7*; CHKO: 17.8±5.9; n=5‐10; *p<0.05 vs. N).BK channels regulate membrane potential and contractility, and NFATc3 regulates its expression in smooth muscle. A reduction in BKα and/or ? expression in pulmonary arteries via NFATc3 could underlie the increased pressure. There was no change in BK ? expression. KO mice showed less BKα mRNA than WT in N. As expected, CH induced a decrease in BKα that was not different from CHKO. Consistently, NFAT activation induced an increase in BKα promoter activity in human PASM cells that was prevented by CsA. This response was lost in cells exposed to 2% O2 for 24 h but basal activity was reduced compared to N. These data demonstrate that NFATc3 is required for CH‐induced pulmonary hypertension and basal BKα mRNA expression. In addition, a reduction in BKα mRNA may be involved in the development of hypertension independently of NFATc3. 1R01HL088151‐01A1/NIH.
The magnitude of ventilatory long term facilitation and the hypoxic ventilatory response is affected by time of day
Authors: Carney L M , Anthouard M N , Lee D S , Badr M S , Mateika J H 
Published: June 2021

PurposeTo determine if the magnitude of ventilatory long term facilitation (vLTF) and the hypoxic ventilatory response (ΔVE/ΔSaO2 ‐ HVR) following exposure to intermittent hypoxia (IH) is affected by time of day.Methods7 male subjects with obstructive sleep apnea were exposed to IH daily for 11 days. The protocol included 12 4‐minute episodes of hypoxia (PETO2 ‐ 50 mmHg, PETCO2 ‐ 3 mmHg above baseline) followed by a 30 minute end‐recovery period. On days 1 and 11 IH was applied in the evening (PM), and in the morning (AM) on days 2‐10. Before and after daily exposure to IH the HVR was measured.ResultsOn Day 1 & 11 (PM) and Day 2 & 10 (AM), VE and the HVR were significantly greater after IH compared to baseline, consistent with our other findings (data not shown ‐ see abstracts from Gerst et al. and Lee et al.). However, vLTF was less (p = 0.004) and the HVR was greater (p = 0.01) during the AM compared to the PM studies before (Days 1 & 2) and after (Days 10 vs. 11) 11 days of IH. Additionally, the vLTF and HVR responses after IH were greater on Days 10 & 11 compared to Days 1 & 2 (vLTF ‐ p = 0.01; HVR ‐ p = 0.05).ConclusionsThe magnitude of vLTF is less and the HVR is greater after AM compared to PM exposure to IH. This relationship persists following chronic IH.FundingNIH (HL‐085537)
Immunohistochemical identification of K+ channel subunits in neurons from chemosensitive regions of rat brainstem
Authors: Putnam Robert W. , Martinez Catalina , Nichols Nicole L. 
Published: June 2021

CO2‐sensitive neurons control breathing and are found in various regions of the brainstem. Neurons within these areas respond to CO2 with different percentages and different magnitudes of changes in firing rate responses to CO2. We propose that neuronal responses to CO2 are different because of differences in the ion channels expressed on neurons in these regions. The current study localized pH‐sensitive K+ channels in two different areas of the brainstem, the solitary tract (SC) (nucleus tractus solitarius, NTS, and dorsal motor nucleus, DMN) and locus coeruleus (LC). Brainstem slices (300µm) were fixed and thin sectioned (20‐40µm). Nissl staining was used to stain all cells and glial fibrillary acidic protein (GFAP)stained astrocytes. Neurons were identified as Nissl positive/GFAP negative. Sections were stained with antibodies for pH‐sensitive subunits of voltage‐sensitive (Kv1.4) and inwardly‐rectifying (Kir2.3 and Kir4.1) K+ channels. We found that Kv1.4 was prevalent on SC neurons (60‐90%), which stained less for Kir2.3 and 4.1 (30‐40%). In contrast, LC neurons stained similarly (50‐60%) for Kv1.4, Kir2.3 and Kir4.1. These data are consistent with an A current (inhibitable by 4 aminopyridine) playing a major role in the CO2 response of SC neurons but both an A current and Kir channels playing a role in the CO2 response of LC neurons.Supported by NIH R01 HL56683 (RWP) and T35 HL007805 (CM).
eNOS induced angiogenesis is blocked by the tyrosine kinase inhibitor Vatalanib (PTK787) in a normoperfused rodent model
Authors: Stone Oliver Andrew , Harper Steven J , Bates David O 
Published: June 2021

Therapeutic angiogenesis has been largely unsuccessful to date. We have shown recently that a combination of growth factor overexpression (Ad.VEGF and Ad.Ang‐1) and physical forces (Ad.eNOS or Prazosin) results in a mature neovasculature (Benest et al 2008). To further investigate the mechanisms of eNOS induced angiogenesis, eNOS was overexpressed in the adult rat mesentery and intravital and confocal imaging used to examine vessel morphology following treatment with PTK787. PTK787 significantly inhibited the eNOS induced increase in functional vessel area (32±4 vs 917±80 vs 159±45%, P<0.001) and vessel density (321±18 vs 549±45 vs 336±25mm−2, P<0.01). In contrast, eNOS in the presence of PTK787, stimulated an increase in conduit vessel density (16‐35μm:63±8 vs 153±31 vs 150 ±16mm−2, P<0.05) and a reduction in exchange vessel density (<16μm:234±17 vs 186±25 vs 397±67 mm−2, P<0.001), resulting in a skewed vessel distribution. Most strikingly, eNOS + PTK787 resulted in the recruitment of vascular smooth muscle cells (VSMC: 0 vs 0 vs 2.2±0.9%, P<0.001) to the neovasculature. These data indicate that VEGFR1/VEGFR2/PDGFR‐β/cKit signalling is required for eNOS stimulated angiogenesis, and for the first time demonstrate increased vessel diameter and VSMC recruitment following PTK787 treatment.All data presented eGFP vs. eNOS vs. eNOS+PTK787; mean±SEM; n=6. Supported by BHF.
Kidney Injury Response to Elevated Blood Pressure vs Increased Intrarenal Ang II in 2K1C Goldblatt Hypertensive Rats
Authors: Carter Brandon J , Martin Victoria L , Navar L Gabriel , Prieto Minolfa C 
Published: June 2021

This study determined the relative role of elevated blood pressure (BP) versus increased Angiotensin II (Ang II) content on the tissue injury response in both kidneys (clipped ‐CK‐ and nonclipped ‐NCK) of two kidney‐one clip (2K1C) Goldblatt hypertensive rats. Kidney injury markers of arterial wall proliferation (α‐sma), fibrosis (Collagen III), inflammation (CD68), cell proliferation‐regeneration (PCNA, Vimentin), and hypoxia (HIF‐α1) were examined using immunohistochemistry on paraffin embedded kidney sections from 2K1C male Sprague‐Dawley (n=6) rats and sham (n=4) rats. After 25 days of unilateral renal clipping (0.25mm), systolic BP increased in 2K1C rats compared to sham rats (184±9 vs.121±6 mmHg). Semi‐quantitation of injury markers showed increased afferent arteriole wall proliferation, macrophages number, and interstitial expansion in both kidneys of 2K1C rats. However, tubular cell proliferation and regeneration were only augmented in the NCK of 2K1C rats compared to CK and sham kidneys. Increased intrarenal Ang II content in both kidneys of 2K1C rats contributes to renal fibrosis and inflammation in Goldblatt hypertension, but preferentially increases of epithelial‐to‐mesenchymal transition and tubule‐cell proliferation in the NCK seems to be associated to the concurrent effect of elevated BP and high intrarenal Ang II content.Support from the NIH and LAMP‐Tulane University.