Laura Shiry

Kansas State University, Manhattan, KS, United States

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Publications (11)22.49 Total impact

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    ABSTRACT: The research question posed was does marginal copper (MC) intake over a protracted period lead to cardiac pathology in rodents either genetically susceptible or nonsusceptible to heart disease? We used the spontaneously hypertensive heart failure (SHHF) rat strain, a genetic model of hypertrophic cardiomyopathy, and the Long-Evans rat strain that does not develop heart disease genetically. Rats from both strains were fed either a control diet with adequate levels of copper (6.7 mg Cu/kg diet) or marginal in copper (2.8 mg Cu/kg diet) for 3, 6, or 10 months. At each time point, electrocardiographic measures were obtained from leads I and aVF, and hearts were processed for histological evaluation by transmission electron microscopy. There were no differences between strain or treatment in terms of mitochondrial or myofibrillar volume density. However, MC rats, regardless of strain and age, had increased lipid droplets in the myocardium. There were strain differences in electrocardiograms with SHHF rats, demonstrating abnormalities in traces, but they were not made any worse by MC intake. However, overall, the rats fed MC, regardless of strain, did demonstrate increased R-wave amplitude and duration in the QRS complex and some changes in P and T waves, which have been reported for severe copper deficiency. We conclude that MC intake over a protracted period is deleterious to cardiac health but that the genetic susceptibility of the heart to other forms of cardiac disease does not hasten or worsen the copper effect.
    Nutrition Research - NUTR RES. 01/2005; 25(7):663-672.
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    ABSTRACT: Sexual dimorphism may occur during the development of hypertension and congestive heart failure (CHF). Male and female spontaneous hypertension heart failure (SHHF) rats with established hypertension, but before CHF (age 5-8 mo) and during cardiac decompensation leading to CHF (age 18-20 mo in male rats and 22-24 mo in female rats), were studied. At 5-8 mo, male SHHF rats showed early activation of the renin-angiotensin system (RAS), as indicated by increased plasma renin activity (PRA) and higher serum angiotensin-converting enzyme activity compared with female rats. The increase in PRA in female rats was delayed compared with males rats, but it reached comparable levels just before CHF. Urinary endothelin excretion was significantly greater in 5- to 8-mo-old female rats compared with age-matched male rats. Urinary endothelin excretion increased in both male and female rats as CHF developed. Plasma atrial natriuretic peptide (ANP) was comparable at both time points, and both genders showed similar, marked increases as CHF developed. In conclusion, male rats show early activation of the RAS, whereas female rats show early activation of the endothelin vasopressor system. During cardiac decompensation, generalized activation of the RAS, endothelin, and ANP systems occurs and is similar in male and female SHHF rats.
    Journal of Applied Physiology 04/2002; 92(3):935-40. · 3.48 Impact Factor
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    ABSTRACT: The proteoglycan, decorin, is a regulator of collagen fibril organization and its resulting functional properties. The temporal and spatial expression of decorin during the progression to heart failure is not well understood and may play a significant role in extracellular matrix remodeling. Decorin and types I and III collagen levels were measured in male Spontaneously Hypertensive Heart Failure (SHHF) and control Wistar-Furth rats at 2 and 8 mo, and at congestive heart failure (CHF). Decorin levels increased in the SHHF rats relative to the control rats in CHF. Type I collagen levels increased while type III levels decreased in the SHHF rats in CHF relative to the age matched controls. The SHHF rats have 48 and 45 KDa isoforms of the decorin core protein expressed at all ages while control Wistar-Furths produced only a 45 KDa form. Decorin was localized in the outer ventricle wall but during CHF, decorin was expressed throughout the ventricular myocardium. Immunogold localization of decorin demonstrated an increased distribution of decorin along the myocardium collagen fibrils at CHF. The enhanced expression and greater distribution of decorin may be linked to extracellular matrix remodeling which occurs with the development of heart failure.
    Connective Tissue Research 02/2002; 43(1):32-43. · 1.79 Impact Factor
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    ABSTRACT: Cytochrome c oxidase (CCO) is an enzyme complex found on the inner mitochondrial membrane and serves as the final electron acceptor in mitochondrial electron transport. Heat shock proteins (HSPs) are involved in the import of nuclear encoded protein subunits into the mitochondria and induce conformational changes to form active enzyme complexes. As both the nuclear and mitochondrial encoded subunits of CCO have been shown to increase in activity and expression in muscle subsequent to artificial loading, and as exercise has been shown to induce HSPs, we sought to determine whether 16-20 weeks of treadmill exercise would result in enhanced CCO subunit expression, and to determine if there was a relationship between this expression and HSP content in medial gastrocnemius muscle of Fischer 344 rats. Our results indicated that endurance training resulted in a 53%, 87% and 80% increase (P<0.05) in the levels of HSP 60, CCO subunit II and CCO subunit VI, respectively. Enzymatic activity of CCO was 84% greater (P<0.05) after endurance training. Mann Whitney U analyses showed that CCO subunit II and VI increased to the same extent as HSP 60 after endurance training. It appears that 16-20 weeks of endurance training leads to uniform increases in CCO subunits and parts of the transport and assembly mechanisms required for CCO enzyme assembly. The similarity among the increases in CCO subunits II and VI protein levels and the increase in CCO enzyme activity suggest that this increase in activity is due to an increase in the amount of CCO enzyme.
    Arbeitsphysiologie 09/2000; 83(1):22-7. · 2.66 Impact Factor
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    ABSTRACT: The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic peptide (ANP) and components of the renin angiotensin system in spontaneously hypertensive heart failure rats (SHHF/Mcc- facp). Development of hypertension was prevented in 3-month-old ovariectomized rats receiving subcutaneous 17 beta -estradiol implants (EST) compared to ovariectomized (OVX) and controls (CON). EST had the least left ventricular hypertrophy, CON were intermediate, and OVX had the most (P<0.05), correlating well with systolic blood pressure. OVX had significantly lower percentage V(1)myosin isoform compared to EST and CON, indicating reversion to a more immature phenotype associated with hypertrophy. Similarly, OVX had decreased percentage left ventricular shortening fraction by echocardiography compared to EST and CON. These changes were not accompanied by alterations in plasma ANP, or in expression of mRNA for left ventricular ANP, renal renin, or hepatic angiotensinogen. Serum angiotensin converting enzyme activity was lower in EST compared to CON or OVX. When 17 beta -estradiol was given to 17-month-old rats that had naturally ceased estrous cycling, there was no effect on hypertension, progression of cardiac functional decline, or survival. In conclusion, estradiol treatment given prior to the development of hypertension in SHHF prevented left ventricular hypertrophy and hypertension. Development of congestive heart failure was not delayed if 17 beta -estradiol was begun in the post-menopausal period. Effectiveness of estrogen therapy may depend on age or whether hypertension is already established at the time treatment is begun.
    Journal of Molecular and Cellular Cardiology 09/1999; 31(8):1527-37. · 5.15 Impact Factor
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    ABSTRACT: Rats with a genetic tendency to develop hypertensive, hypertrophic cardiomyopathy were fed copper-deficient diets and their cardiac responses were investigated. Five male weanling rats of the Long-Evans and SHHF/Mcc-fa(cp) strains were randomly selected to receive diets containing either adequate quantities of copper (94.5 micromol Cu/kg diet) or reduced quantities of copper (<15.8 micromol Cu/kg diet) for 6 weeks, (n=5 within each group). Echocardiograms and electrocardiograms were recorded and analyzed at the end of the 6-week interval. Electrocardiograms from copper deficient groups showed longer Q-T intervals and increased QRS amplitudes than controls. Both the copper deficient and control SHHF groups demonstrated significant QRS complex prolongation compared to Long-Evans rats. Echocardiography analysis showed significant increases in left ventricular area, free wall dimension, and myocardial cross-sectional areas in rats fed a copper deficient diet. The frequency of systolic cardiac murmurs increased in copper deficient rats and were related to the presence of valvular regurgitation as determined from echocardiography. However, the data do not suggest that a copper-deficient diet fed to a strain of rats genetically susceptible to heart disease later in life, hastens or worsens the onset of cardiac disease. The genetic predisposition and copper-deficient states exert independent effects upon the heart.
    Journal of the American College of Nutrition 02/1999; 18(1):51-60. · 1.74 Impact Factor
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    ABSTRACT: A study was conducted to evaluate the influence of copper and iron deficiencies upon femur mineral content and biomechanical properties. Radiogrametry and single photon absorptiometry were used to evaluate femur bone mass. Long-Evans male rats were fed purified diets either adequate or deficient in the selected element from weanling until 9 weeks of age. Results demonstrate that in rats fed both the copper and iron restricted diets, the breaking strength was significantly decreased in both femurs. Lower levels of iron and copper were observed in the livers of the respected trace element restricted groups, and femur iron and copper were depressed in both of these groups as well. Femur Cu:Zn was decreased in the copper deficient group and femur zinc levels were elevated in the iron deficient group. Copper and iron restricted rats had smaller cortical and, larger medullary area in a portion of the femur, 1/4 from the distal end, as determined by radiogrametry, but there were no differences at the mid point or proximal portions of the femurs. The influence of iron restriction upon the decreased bone biomechanical strength is a novel finding and deserves further attention, in that iron deficiency anemia is a prevalent public health problem. J. Trace Elem. Exp. Med. 10:197–203, 1997. © 1997 Wiley-Liss, Inc.
    The Journal of Trace Elements in Experimental Medicine 12/1998; 10(3):197 - 203.
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    ABSTRACT: Hearts from rats fed a copper-deficient (Cu-) diet have decreased levels of nuclear-encoded peptides of cytochrome c oxidase (CCO). Studies were conducted to determine whether iron deficiency would lead to a similar finding, whether mRNA transcripts and the chaperonin heat shock proteins (HSP) 60 and 70 from hearts of Cu- rats were decreased as compared with copper-adequate controls and whether synthesis of mitochondrial and nuclear encoded peptides differed as affected by diet copper. In study 1, weanling rats were assigned to one of three groups (n = 6 in each group): (1) control copper and iron adequate fed rats; (2) Cu- rats and (3) iron-deficient (Fe-) rats. Western blotting of nonmyofibrillar cardiac proteins revealed that the nuclear encoded peptides of CCO from the Cu- rats were markedly decreased as compared with control and Fe- rats. Mitochondrial encoded subunits did not appear to differ by treatment groups. Iron-deficient rats had similar nuclear encoded peptide levels as those of controls. In study 2, mRNA transcripts from Cu- (n = 4) and control copper adequate (n = 4) rats did not appear to differ for subunits II and IV, which correspond to mitochondrial and nuclear encoded subunits, respectively. In study 3, levels of HSP 60 and 70 from hearts of Cu- rats (n = 3) did not differ from Cu+ rats (n = 3). In study 4, infusion of 3H-(4,5)-leucine into the hearts of Cu+ and Cu- rats suggested there was no difference in synthesis of the nuclear encoded peptides by copper status and some indication there was enhanced breakdown of the nuclear encoded peptides among the Cu- rats. As expected, more isotope was incorporated into the mitochondria of Cu- rats than Cu+ rats. These results demonstrate an independent effect of copper upon the apparent decrease in the nuclear encoded subunits of CCO, the effect of copper upon the CCO subunits is probably post-transcriptional and that translocation of the nuclear encoded subunits from the ribosomes to the mitochondria via the chaperonin proteins is not a primary defect in explaining these observations in hearts from Cu- rats and synthesis of the nuclear encoded subunits of CCO in not impaired in copper deficiency.
    Comparative biochemistry and physiology. Part A, Physiology 06/1997; 117(1):77-87. · 2.17 Impact Factor
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    ABSTRACT: This study determined if reported decreases in the delta subunit of ATP synthase and nuclear-encoded cytochrome c oxidase subunits in hearts of copper-deficient rats were secondary to the heart disease pathology or due to lack of the trace element. Male weanling Long-Evans rats were randomly divided into six groups: rats fed a copper-adequate or copper-deficient diet (with free access) with or without 5% dimethyl sulfoxide (DMSO) in the drinking water and rats pair-fed the copper-adequate or copper-deficient diet without DMSO treatment. After 4 wk, rats in the groups fed the copper-deficient diet had lower liver superoxide dismutase and heart cytochrome c oxidase activities compared with groups fed the copper-adequate diet. Administration of DMSO, an antioxidant, and energy restriction (pair-feeding) partially blocked cardiac hypertrophy in rats fed the copper-deficient diet. Greater mitochondrial volume density and mitochondrial:myofibrillar ratio and disrupted myofibrils and basal laminae were observed in the hearts from rats fed the copper-deficient diet and not treated with DMSO compared with hearts from groups fed the copper-adequate diet. The DMSO-treated rats fed the copper-deficient diet had hearts with intact structure but enlarged mitochondria compared with other groups fed the copper-deficient diet. The delta subunit of ATP synthase and the nuclear-encoded cytochrome c oxidase subunits IV and V were depressed in rats fed a copper-deficient diet regardless of antioxidant treatment and pair-feeding. These data suggest that the effects of copper deficiency upon ATP synthase and cytochrome c oxidase proteins are not due to the cardiac pathology.
    Journal of Nutrition 07/1994; 124(6):789-803. · 4.20 Impact Factor
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    ABSTRACT: Cardiac nonmyofibrillar proteins from copper-deficient rats appear to have diminished quantity of selected peptides. Identification of some of these peptides was the objective of the present study. Male weanling Long-Evans rats were fed either copper-adequate (n=6) or copper-deficient (n=6) diets for 5 wk. At the end of 5 wk, the rat hearts were removed, quick frozen in liquid nitrogen, and non-myofibrillar proteins separated using sodium-dodecyl-sulfate poly-acrylamide gel electrophoresis (SDS-PAGE). A peptide in the 16-kDa mol-wt region was diminished in copper-deficient rats. Blotting of gels to an Immobilon-P membrane and subsequent sequencing of the amino acids identified the peptide as the δ subunit of mitochondrial ATP synthase. Blotting of gels to nitrocellulose followed by Western blot assay for cytochrome C oxidase using antibodies against the enzyme complex revealed decreased protein content in the copper-deficient rat for this enzyme, primarily the nuclear encoded subunits.
    Biological Trace Element Research 36(3):271-282. · 1.31 Impact Factor
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    ABSTRACT: This study determined if reported decreases in the 6 subunit of ATP synthase and nuclear- encoded cytochrome c oxidase subunits in hearts of copper-deficient rats were secondary to the heart disease pathology or due to lack of the trace element. Male weanling Long-Evans rats were randomly divided into six groups: rats fed a copper-adequate or copper- deficient diet (with free access) with or without 5% dimethyl sulfoxide (DMSO) in the drinking water and rats pair-fed the copper-adequate or copper-deficient diet without DMSO treatment. After 4 wk, rats in the groups fed the copper-deficient diet had lower liver su- peroxide dismutase and heart cytochrome c oxidase ac tivities compared with groups fed the copper-adequate diet. Administration of DMSO, an antioxidant, and energy restriction (pair-feeding) partially blocked cardiac hypertrophy in rats fed the copper-deficient diet. Greater mitochondria! volume density and mitochondria!: myo- fibrillar ratio and disrupted myofibrils and basal laminae were observed in the hearts from rats fed the copper- deficient diet and not treated with DMSO compared with hearts from groups fed the copper-adequate diet. The DMSO-treated rats fed the copper-deficient diet had hearts with intact structure but enlarged mitochondria compared with other groups fed the copper-deficient diet. The ôsubunit of ATP synthase and the nuclear- encoded cytochrome c oxidase subunits IV and V were depressed in rats fed a copper-deficient diet regardless of antioxidant treatment and pair-feeding. These data suggest that the effects of copper deficiency upon ATP synthase and cytochrome c oxidase proteins are not due to the cardiac pathology. J. Nutr. 124: 789-803, 1994.

Publication Stats

139 Citations
22.49 Total Impact Points

Institutions

  • 2002
    • Kansas State University
      • Department of Human Nutrition
      Manhattan, KS, United States
  • 1994–2002
    • The Ohio State University
      • • Department of Veterinary Biosciences
      • • Department of Human Nutrition
      • • Department of Physical Medicine and Rehabilitation
      Columbus, OH, United States