Evelyn Bayna - Academia.edu (original) (raw)

Papers by Evelyn Bayna

Telemetry tracings from a mouse that died 39 days after weekly LPS 10 mg/kg i.p. Each st... more Telemetry tracings from a mouse that died 39 days after weekly LPS 10 mg/kg i.p. Each strip is 2.5 seconds. The mouse was in sinus rhythm 552 beats per minute (bpm) at baseline at 1:00 p.m. Two hours later, an accelerated idioventricular rhythm (AIVR) or slow ventricular tachycardia (VT) with fusion complexes with sinus beats developed (3:01 pm), with an AIVR or slow VT at 648 bpm at 3:02 pm. The mouse returned to sinus rhythm at 625 bpm at 4:00 pm. One hour later, there was sinus exit block with slow idioventricular escape rhythm (4:56 pm), and then high degree AV block (5:02 pm) shortly before death.</p

Expression of fibrosis-related genes in the left ventricle measured by QRT-PCR (mean+SEM... more Expression of fibrosis-related genes in the left ventricle measured by QRT-PCR (mean+SEM) after 15 weeks of weekly i.p. injections of saline (control, n = 7), LPS (10 mg/kg, n = 6), saline with losartan (20 mg/kg/day in drinking water) (n = 6), or LPS with losartan (n = 5). LPS increased LV expression of fibrosis-related genes including collagen Iα1, collagen IIIα1, MMP2, MMP9, TIMP1 and periostin (P<0.05, 2 way ANOVA). Adding the AT1R inhibitor losartan to the drinking water prevented LPS-induced increases in collagen Iα1 and MMP2 and attenuated LPS-induced increases in collagen IIIα1 and MMP9 (P<0.05 for interaction between LPS and losartan), but had no effect on TIMP-1 or periostin. Losartan alone had no effect.</p

Cardiac expression of miR-29c (mean + SEM) measured by QRT-PCR in mice injected with i.p... more Cardiac expression of miR-29c (mean + SEM) measured by QRT-PCR in mice injected with i.p. saline (time 0, control, n = 3), 3 days after LPS (10 mg/kg i.p.) (n = 3), or 7 days after LPS (10 mg/kg i.p.) (n = 3). There was a significant decrease in miR-29c with LPS (P = 0.02, one way ANOVA). Multiple comparisons (Holm-Sidak Test) showed that when compared with control, the decrease in miR-29c was significant at 3 days and at 7 days (*P<0.05), with no difference between 3 days and 7 days.</p

Picrosirius staining in the left ventricular wall increases after 2 or 4 weeks of intrap... more Picrosirius staining in the left ventricular wall increases after 2 or 4 weeks of intraperitoneal LPS (10 mg/kg/week), compared with a saline control mouse.</p

Survival with weekly injections of saline or LPS.</p

Cardiac miRNA expression profiling in C57/Bl6 mice injected with i.p. saline (time 0, co... more Cardiac miRNA expression profiling in C57/Bl6 mice injected with i.p. saline (time 0, control), or with hearts harvested 3 or 7 days after LPS (10 mg/kg) (n = 3 mice each time period). Heat map shows miR expression that increased (red), did not change (black) or decreased (green) for three mice each at time 0 (control, columns 1–3), 3 days after LPS (columns 4–6), and 7 days after LPS (columns 7–9), with differences between the three time periods with a p-value of<0.10 (ANOVA).</p

NOX 2 = NADPH Oxidase 2, MMP = matrix metaloproteinase, TIMP = tissue inhibitors of MMPs... more NOX 2 = NADPH Oxidase 2, MMP = matrix metaloproteinase, TIMP = tissue inhibitors of MMPs.Time course for changes in fibrosis related factors in the left ventricle after injection of LPS (10 mg/kg/week i.p.) compared with control (saline injection).</p

Expression of the cytokines IL-1β, IL-6, TNF-α and TGF-β (mean+SEM percent of control) w... more Expression of the cytokines IL-1β, IL-6, TNF-α and TGF-β (mean+SEM percent of control) were measured in the left ventricle after 3 months of LPS (20 mg/kg/week i.p, n = 5) or saline (n = 6). There was a significant increase in IL-6 (P<0.001), but no significant change in IL-1β, TNF-α, or TGF-β.</p

Data mean ± SEM for saline control group (n = 7), LPS 0.1, 1.0, and 10 mg/kg/week (n = 8... more Data mean ± SEM for saline control group (n = 7), LPS 0.1, 1.0, and 10 mg/kg/week (n = 8 for each LPS dose). P values for one way ANOVA, ns = not significant.*P<0.05 vs saline;†P<0.05 vs LPS 10 mg/kg/week with multiple comparisons by Holm-Sidak method.</p

Data mean ± SEM for saline control (n = 24), LPS low dose (0.1–1.0 mg/kg/week, n = 16), ... more Data mean ± SEM for saline control (n = 24), LPS low dose (0.1–1.0 mg/kg/week, n = 16), or LPS moderate dose (10–20 mg/kg/week, n = 23). BW = body weight, HW = heart weight, LV = left ventricle. None of the weights differed significantly between groups (P = ns, one way ANOVA).</p

$Research paper thumbnail of LPS increases collagen fraction area in 2–4 weeks$

Collagen fraction area expressed as percent of left ventricle sections stained positive ... more Collagen fraction area expressed as percent of left ventricle sections stained positive with picrosirius acid (mean + SEM) for mice injected with i.p. saline (Control, n = 7), or LPS 10 mg/kg/week for 1 week (n = 6), 2 weeks (n = 6), or 4 weeks (n = 5). There was a significant increase in collagen fraction area after injection of LPS (P<0.001, one way ANOVA). Multiple comparisons using the Holm-Sidak Test showed significant increases in collagen fraction area at 2 weeks and 4 weeks compared with Control or 1 week (*P<0.05), with no significant difference between 2 week and 4 weeks, or between Control and 1 week (P = ns).</p

Isolated adult cardiac fibroblasts were exposed to vehicle or LPS in concentrations of 0... more Isolated adult cardiac fibroblasts were exposed to vehicle or LPS in concentrations of 0.1, 1.0, or 10 ng/ml for 48 hours. There was a dose dependent increase in IL-6 (P<0.001, ANOVA, each bar mean+SEM, n = 4). All LPS doses were higher than control and increased significantly with each increment in dose (P<0.05). LPS caused no significant change in TGF-β.</p

Percent collagen fraction area in the left ventricle by picrosirius red staining (mean+S... more Percent collagen fraction area in the left ventricle by picrosirius red staining (mean+SEM, n = 5) increased with LPS (P<0.001, 2 way ANOVA). LPS effects were not affected when the AT1R inhibitor losartan was added to the drinking water (P = 0.80). Losartan alone had no effect. There was no significant interaction between LPS and losartan (P = 0.70).</p

$Research paper thumbnail of LPS dose-dependently increased percent collagen fraction area of the left ventricle$

Percent collagen fraction area (mean+SEM) measured by picrosirius staining of the left v... more Percent collagen fraction area (mean+SEM) measured by picrosirius staining of the left ventricle increased 12–15 weeks after weekly i.p. injections of low dose LPS (0.5±0.1 mg/kg, n = 15) or moderate dose LPS (12±1 mg/kg, n = 15) compared with saline (control, n = 17) (P<0.001, one way ANOVA). There was a greater increase with moderate dose LPS than with low dose LPS (P<0.05).</p

Panel A. Picrosirius staining was greater in a mouse injected with LPS 10 mg/kg/week for... more Panel A. Picrosirius staining was greater in a mouse injected with LPS 10 mg/kg/week for 12 weeks, compared with a control mouse injected weekly with saline. Panel B. H & E staining showed evidence of myofiber loss with replacement by fibrosis (arrow) after 15 weeks of LPS 20 mg/kg/week.</p

Panel A: LV fractional shortening and heart rate (beats per minute, bpm) measured before... more Panel A: LV fractional shortening and heart rate (beats per minute, bpm) measured before (0 hours), and 6 and 24 hours after i.p. injection of saline (control), LPS 1, 10, or 20 mg/kg (each bar, mean+SEM, n = 6). There was a mild decrease in LV fractional shortening after 6 hours with LPS 10 and 20 mg/kg (*P<0.05 vs LPS 1 mg/kg or control) that resolved by 24 hours. Panel B: LV fractional shortening, heart rate, LV internal diameter in diastole (LVIDd), and LV mass measured after 2 months of weekly i.p. injections of saline (n = 11), LPS 10 mg/kg (n = 8) and LPS 20 mg/kg (n = 12), and after 3 months of weekly i.p. injections of saline (n = 13) or LPS 20 mg/kg (n = 5). There were a few minor changes with LPS 20 mg/kg (*P<0.05 compared with control), but no significant decrease in LV function, LV dilation, or change in LV mass.</p

Molecular and Cellular Biochemistry, 1986

Recent results from our laboratory suggest that a variety of cellular interactions during develop... more Recent results from our laboratory suggest that a variety of cellular interactions during development are mediated, in part, by the binding of a cell surface enzyme, galactosyltransferase (GalTase), to its specific lactosaminoglycan (LAG) substrate on adjacent cell surfaces and in the extracellular matrix. Our present interest in surface GalTase developed from earlier biochemical studies of a series of morphogenetic mutations in the mouse which map to the T/t-complex. These studies identified a specific defect in the regulation of surface GalTase activity on morphogenetically abnormal cells, while eight other enzymes showed normal activity. This led us to consider the unique function of surface GalTase in those cell interactions that are influenced by mutations of the T/t-complex. By using a multidisciplinary approach, which included genetic, biochemical and immunological probes, we have found that GalTase functions as a surface receptor during fertilization, early embryonic cell adhesions, and embryonic cell migration on basal lamina matrices. Recently, we have examined the expression of surface GalTase during spermatogenesis, as well as the fate of sperm GalTase following the acrosome reaction. This paper summarizes the results of these studies, as well as others, which suggest that GalTase functions as a surface receptor during those cell interactions regulated by the T/tcomplex alleles.

Journal of the American College of Cardiology, 2007

We investigated whether lipopolysaccharide (LPS), a proximate cause of inflammation, activates ca... more We investigated whether lipopolysaccharide (LPS), a proximate cause of inflammation, activates calcineurin in cardiac myocytes and if calcineurin regulates apoptosis in this setting. Background Calcineurin regulates myocardial growth and hypertrophy, but its role in inflammation is unknown. Calcineurin has proapoptotic or antiapoptotic effects depending on the stimuli. Methods Calcineurin activity was measured in left ventricular myocytes from adult Sprague Dawley rats. Cardiac apoptosis was measured by terminal deoxy-nucleotidyl transferase-mediated dUTP nick end-labeling staining and caspase-3 activity after in vitro and in vivo exposure to LPS. Results Lipopolysaccharide increased calcineurin activity in myocytes over 1 to 24 h (t 1/2 ϭ 4.8 h) with an EC 50 of 0.80 ng/ml LPS (p Ͻ 0.05, n ϭ 4). The LPS (10 ng/ml) effects were mimicked by angiotensin II (Ang II) (100 nmol/l); both increased calcineurin activity and induced apoptosis without additive effects (p Ͻ 0.05, n ϭ 5 to 9). Lipopolysaccharide and/or Ang II effects were prevented by 1 h pre-treatment with an Ang II type 1 receptor blocker (losartan, 1 mol/l), calcineurin inhibitor (cyclosporin A, 0.5 mol/l), calcium chelator (1,2-Bis(2-amino-5-fluorophenoxy)ethane-N,N,N=,N=-tetraacetic acid tetrakis(acetoxymethyl) ester, 0.1 mol/l), or by inhibiting sarcoplasmic reticulum (SR) calcium (Ca)-ATPase (thapsigargin, 1 mol/l) or SR calcium release channel (ryanodine, 1 mol/l). Left ventricular apoptosis increased from 4 to 24 h after LPS (1 mg/kg intravenously) in vivo, but not in rats pre-treated with cyclosporin A (20 mg/kg/day subcutaneously) for 3 days (p Ͻ 0.05, n ϭ 5). Conclusions In cardiac myocytes, LPS activates calcineurin in association with apoptosis by Ang II and SR calcium-dependent mechanisms. This expands the paradigm for cardiac calcineurin to be activated by low levels of LPS in inflammation and chronic conditions (e.g., infections, smoking, and heart failure).

Journal of Molecular and Cellular Cardiology, 1997

The isolated myocyte is useful for examining the direct cardiac effects of substances such as lip... more The isolated myocyte is useful for examining the direct cardiac effects of substances such as lipopolysaccharide (LPS) and cytokines. However, the digestive enzymes used for standard cell isolation procedures are contaminated by several hundred ng/ml LPS. We depyrogenated the digestive enzymes with a series of Triton X-114 and Polymyxin B washes to remove 99.7-99.9% of the LPS. This lowered LPS contamination levels from 100-300 ng/ml to 0.15-0.70 ng/ml, while maintaining good quality cell isolations from the left ventricle of New Zealand white rabbits. We evaluated whether brief exposure to LPS contaminant levels, as occur during standard cell isolations, induces LPS tolerance. Cardiac myocytes (isolated with depyrogenated enzymes) were pre-exposed to 100 ng/ml LPS for 1 h, washed, then exposed to a challenge dose with 100 ng/ml LPS. The LPS challenge dose induced a time-dependent decrease in cell shortening over 6 h in myocytes without pre-exposure, but not in myocytes pre-exposed to an earlier dose of LPS. We examined whether LPS tolerance develops in myocytes isolated with untreated enzymes, compared with depyrogenated enzymes. In myocytes isolated with untreated enzymes, there was a significant decrease in cell shortening after 6 h exposure to 1000-10 000 ng/ml LPS. In myocytes isolated with depyrogenated enzymes, it required only 5-50 ng/ml LPS to induce a comparable cardiac depression. We conclude that brief exposure to LPS contaminant levels, which occur with standard cell isolation procedures, induces a hyporesponsiveness or tolerance to subsequent doses of LPS in isolated cardiac myocytes.

Cell, 1988

Cell surface (!I-1,4 galactosyltransferase (GalTase) is shown to mediate intercellular adhesions ... more Cell surface (!I-1,4 galactosyltransferase (GalTase) is shown to mediate intercellular adhesions between embryonal carcinoma (EC) cells and specifically during late morula compaction in the preimplantation mouse embryo. Monospecific anti-GalTase IgG raised against affinity-purified bovine (3-1,4 GalTase recognizes F9 EC cell GalTase as judged by immunoprecipitation and inhibition of GalTase activity, as well as by immunoprecipitation of a single 52 kd metabolically labeled membrane protein. Anti-GalTase IgG inhibits cell adhesions between EC cells, dissociates compacted mouse morulae, and inhibits blastocyst formation. Anti-GalTase IgG specifically inhibits cell adhesions during late morula compaction, coincident with a peak of surface GalTase activity as determined by direct enzyme assay. On EC cells, GalTase activity can be proteolytically released from intact cells, and is localized by indirect immunofluorescence to areas of intercellular contact, consistent with its proposed role in cell adhesion. b-1,4 GalTase is the first cell adhesion molecule identified that participates during late morula compaction, subsequent to uvomorulin function.

Survival with weekly injections of saline or LPS.</p

$Research paper thumbnail of LPS increases collagen fraction area in 2–4 weeks$

$Research paper thumbnail of LPS dose-dependently increased percent collagen fraction area of the left ventricle$

Molecular and Cellular Biochemistry, 1986

Journal of the American College of Cardiology, 2007

Journal of Molecular and Cellular Cardiology, 1997

Cell, 1988