Progress 10/01/03 to 09/30/08
Outputs
OUTPUTS: Results have been disseminated to the scientific community through publications (see Publications Section) and recently at the tri-society International Conference of the Internationl society of Trace Element Research in the Human (ISTERH), Nordic Trace Element society (NTES) and the Hellenic Trace Element Society (HTES) in Crete, Greece as an invited presentation. PARTICIPANTS: PARTICIPANTS: Anastasia Z. Kalea, doctoral student and postdoctoral fellow,Department of Food Science and Human Nutrition, University of Maine Dale Schuschke, Professor of Physiology, University of Louisville, School of Medicine, Nikolaos Karamanos, Professor of Chemistry, University of Patras, Patras, Greece, Fotini Lamari,Postdoctoral Fellow, Department of Chemistry, University of Patras, Patras, Greece TARGET AUDIENCES: TARGET AUDIENCES: Graduate and undergraduate students working on the project aquiring skills and knowledge on bio-sensors, functional and biochemical measurements. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Cardiovascular disease (CVD)is the leading cause of death in the U.S.. With our studies we have demonstrated for the first time that manganese content of the diet affects the biomechanical properties of blood vessels by regulating vascular tone; this may have implications on blood pressure regulation, one of the risk factors for CVD. Presence of manganese in the diet, aids in vasorelaxation by possibly inhibiting the synthesis or activity of a vasoconstrictor. Additionally, dietary manganese affects the concentration, composition and sulfation pattern of arterial glycosaminoglycans such as heparan sulfate, thus altering cell-membrane binding ability to extracellular ligands leading to modifications in signal-transduction pathways and thus arterial functional properties.Thus our knowledge in this area has improved and has had impacts on the graduate students involved in the project. It helped them aquire new skills and knowledge and also aided the scientific community in documenting the mechanism of action of manganese on arterial functional properties, structure and metabolism and its possible role on blood pressure regulation. Our findings encourage new research in this area and possible funding by governmental bodies, private foundations, pharmaceutical, supplement and food companies . At the present time, the National Academy of Science (NAS)has set an Adequate Requirement (AI)for Manganese. Studies similar to ours may help the NAS set an RDA for manganese in the future. The dietetics community, and health care providers may want to ensure optimal manganese nutrition in their clients or patients. The supplement industry will be also interested in the results from this study
Publications
- Klimis-Zacas D and Kalea AZ. Manganese: Modulator of arterial function and metabolism: a review.Cell Biology and Toxicology, 2009(in print)
- Kalea AZ, Clark K, Schuschke DA, Kristo AS & Klimis-Zacas D. Dietary enrichment with wild blueberries (Vaccinium angustifolium) affects the vasomotor pathways in young Spontaneously Hypertensive Rats (SHR). Journal of Nutritional Biochemistry, 2009(in print)
- Kalea AZ, Clark K, Schuschke DA & Klimis-Zacas D. Endothelium-mediated vasoreactivity is affected by dietary consumption of wild blueberries in Sprague-Dawley rats. Journal of Medicinal Food, 2009(in print)
- Magdalini A. Papandreou, Andriana Dimakopoulou, Paul Cordopatis, Dorothy Klimis-Zacas , Marigoula Margarity, and Fotini N. , Effect of a Polyphenol-rich Blueberry Extract on Cognitive Performance, Brain Antioxidant Markers and Acetylcholinesterase Activity in mice. Behavioural Brain Research, 2009(in print)
- Klimis-Zacas D & Kalea AZ. Manganese and arterial functional properties. Cell Biology and Toxicology 24(2/3), 2008(in print)
- Elizabeth Dodge and Dorothy Klimis-Zacas, The impact of organic and conventional food systems on health and the environment: A research review, J. Ecology and Nutrition (Under review, 2008)
- Kristo AS, Kalea AZ, Schuschke D.A. & Klimis-Zacas D. Effect of wild blueberries (V. angustifolium) on endothelium-dependent vasodilation in Spontaneously Hypertensive (SHR) and normotensive, Wistar Kyoto (WK) rats, FASEB J. 22:700.27, 2008.
- Kristo AS, Lamari, F, Karamanos N, & Klimis-Zacas, D. Wild Blueberry (V. angustifolium) Consumption Alters the Composition and Structure of Glycosaminoglycans (GAGs) in Spontaneously Hypertensive Rats (SHR),FASEB J., 2009
- Del' Bo C, Riso P, Ciappellano S, Gardana C, Porrini M, & Klimis-Zacas D. Wild Blueberries (V. angustifolium) Protect Lymphocytes against DNA Damage in Sprague Dawley Rats, FASEB J., 2009
|
Progress 10/01/06 to 09/30/07
Outputs
OUTPUTS: Dietary manganese affects the structure and integrity of blood vessels, as well as vessel predisposition to endothelial dysfunction and cardiovascular disease. Our outputs during the life of the project are as follows: Dietary manganese influences the contractile machinery of vascular smooth muscle cells and regulates the bioactivity of endothelium-mediated vasodilators to affect agonist-induced signaling pathways that participate in the regulation of vasomotor tone. This suggests possibilities for dietary intervention in blood pressure regulation. Additionally, dietary manganese affects the concentration, composition and sulfation pattern of arterial glycosaminoglycans such as heparin sulfate, thus altering cell-membrane binding ability to extracellular ligands leading to modifications in signal-transduction pathways and thus arterial functional properties. Results have been disseminated to the scientific community through publications (see Publications Section) and
recently at the tri-society International Conference of the Internationl society of Trace Element Research in the Human (ISTERH), Nordic Trace Element society (NTES) and the Hellenic Trace Element Society (HTES) in Crete, Greece as an invited presentation.
PARTICIPANTS: Anastasia Z. Kalea, doctoral student and postdoctoral fellow,Department of Food Science and Human Nutrition, University of Maine Dale Schuschke, Professor of Physiology, University of Louisville, School of Medicine, Nikolaos Karamanos, Professor of Chemistry, University of Patras, Patras, Greece, Fotini Lamari,Postdoctoral Fellow, Department of Chemistry, University of Patras, Patras, Greece
TARGET AUDIENCES: Graduate and undergraduate students working on the project aquiring skills and knowledge on bio-sensors, functional and biochemical measurements.
Impacts
Cardiovascular disease (CVD)is the leading cause of death in the U.S. with our studies we have demonstrated for the first time that depending on the dietary level of manganese it affects the biomechanical properties of blood vessels by regulating vascular tone and may have implications on blood pressure regulation, one of the risk factors for CVD. Presence of manganese in the diet, aids in vasorelaxation by possibly inhibiting the synthesis or activity of a vasoconstrictor. Thus our knowledge in this area has improved and has had impacts on the graduate students aquiring new skills and knowledge and the scientific community in sheding new light on the role of this trace element and its mechanism of action on the arterial functional properties, structure and metabolism and its possible role on blood pressure regulation. This encourages new research in this area and increased funding by the Governement,private foundations, pharmaceutical, supplement or food companies .
At the present time, the National Academy of Science (NAS)has set an Adequate Requirement (AI)for Manganese. Studies similar to ours may help the NAS set an RDA for manganese in the future. The dietetics community, and health care providers may want to ensure optimal manganese nutrition in their clients or patients. The supplement industry will be also interested in the results from this study
Publications
- 11. Clark K., Kalea A.Z., Schuschke D, Harris P.D. & Klimis-Zacas, D. Effect of dietary blueberries on endothelium-dependent vasodilation in spontaneously hypertensive rats, late breaking abstract, FASEB-Experimental Biology 2006 Meetings, San Francisco, April, 2006.
- 12. Ciappellano S., C. Gardana, F. Galvano, & D. Klimis-Zacas, In vitro absorption of anthocyanins present in wild blueberry (Vaccinium angustifolium) powder, XXXIV National Congress of the Italian Society for Human Nutrition, Rimini, Italy, November, 2006.
- *13. Klimis-Zacas, D., and Kalea A.Z., Manganese, Regulator of Vasomotor Tone and Arterial Glycosaminoglycan Metabolism, Joint Conference of the International Society of Trace Element Research, Nordic Trace Element Society and the Hellenic Trace Element Society, Crete, Greece, October 21-26, 2007.
- 14. Papandreou M., Dimakopoulou A., Cordopatis P., Klimis-Zacas D., Margariti M., & Lamari,F. N., Effect of Anthocyanin-Rich Wild Blueberry Extract (V. Angustifolium) on the Antioxidant and Behavioral Aspects of Mice, 59th Annual Meeting of the Hellenic Society of Biochemistry and Molecular Biology, Athens, December 7-9, 2007.
- 6. D. Klimis-Zacas, Annual Editions: Nutrition 2005/2006, McGraw-Hill/Dushkin, 2005
- 7. D. klimis-Zacas, Annual Editions: Nutrition 2006/2007, McGraw-Hill/Dushkin, 2006 8. D. Klimis-Zacas 2007, Annual Editions: Nutrition 2007/2008, McGraw-Hill/Dushkin, 2007
- 9. D.Klimis-Zacas, Kalea, A.Z. and I. Wolinsky. Nutritional Issues of Cardiovascular Disease in Women. In Klimis-Zacas, D. and I. Wolinsky (eds) Nutritional Concerns for Women, 2nd edition, CRC Press Inc., Boca Raton, FL. 2003. Other publications
- 1. Klimis-Zacas, D., Chocolate the Divine, Healthy U, Wellness Newsletter, University of Maine, February 2005.
- 2. Klimis-Zacas, D., Dietary Fat: The Good, the Bad and the Ugly, Healthy U, Wellness Newsletter, University of Maine, October 2005.
- *1. Kalea A.Z., Norton C., Harris P.D. & Klimis-Zacas, D. Manganese (Mn) enhances endothelial modulation of a1 adrenoreceptor (AR) mediated contraction of vascular smooth muscle (VSM) in rat aorta, FASEB J. 17(4), A335, 2003.
- 2. Kalea A.Z., Norton C., Harris P.D. & Klimis-Zacas D. Whole wild blueberries suppress a1 adrenergic agonist induced contraction in rat aorta, FASEB J. 17(4): A334, 2003.
- 3. Norton C., Kalea A.Z., Harris P.D. & Klimis-Zacas D. Whole wild blueberries affect the vascular contractile machinery in the Sprague-Dawley rat, FASEB J. 16(4): A334, 2003.
- *4. Kalea A.Z., Lamari F., Karamanos N.K. & Klimis-Zacas, D. Dietary Manganese affects heparan sulfate concentration and sulfation pattern in Sprague-Dawley rat aorta, Federation of the European Connective Tissue Societies (FECTs) XIX, PB(26): 79, 2004.
- 5. Kalea A.Z., Lamari F.N., Cordopatis P., Klimis-Zacas, D., & Karamanos N. K. The dietary effect of wild blueberries on the structure, and macromolecular composition of rat arteries, 5th Conference on Medicinal Foods: Drug Design and Development, pg.70, 2004.
- *6. Kalea A. Z, Lamari F. N., Karamanos N. K., & Klimis-Zacas, D.,, Dietary Manganese Affects Total Heparan Sulphate Glycosaminoglycan (HSGAG)Concentration and Sulfation Pattern in Sprague-Dawley Rat Aorta, Proccedings U.M.Graduate Student Research, pg.25, 2004.
- *7. Klimis-Zacas D., Kalea A.Z., Lamari F.N., Theocharis A. D., & Karamanos N. K. Rat arterial heparan sulfate, structure and concentration is influenced by dietary manganese consumption, 56th Conference of the Hellenic Society of Biochemistry and Molecular Biology, pg.57, 2004.
- 8. Kalea A.Z., Lamari F., Theocharis A.D., Karamanos N.K., Klimis-Zacas, D. Dietary blueberries affect the composition and structure of rat aortic extracellular matrix, FASEB J. 19(4): A451, 2005.
- *9. Klimis-Zacas, D., Kalea A.Z., Lamari F. N., Theocharis A.D., & Karamanos N.K. The effect of dietary consumption of blueberries and different dietary levels of manganese on concentration,composition and structure of glycosaminoglycans in rat aorta.. 7th Annual Meeting of the Hellenic Research Society for Connective Tissue and Matrix Biology, p.40, 2005. *10. Kalea A.Z., Schuschke D, Harris P.D. & Klimis-Zacas, D. Cyclo-oxygenase inhibition restores endothelium-dependent vasodilation in manganese deficiency FASEB J. 20(4): A465.10, 2006.
- Meeting proceedings Papandreou M.A., Efthimiopulos S., Cordopatis P., Klimis-Zacas D., Margariti M. & Lamari F.N. Inhibitory activity on amyloid-beta protein aggregation and antioxidant properties of blueberry extracts, Hellenic Society of Pharmacology Proceedings, March, 2006.
- A.Z. Kalea, Lamari F., Theocharis A.D., Cordopatis P., Schuschke D. A., Karamanos N.K., Klimis-Zacas D. Wild blueberry (Vaccinium angustifolium) consumption affects the composition and structure of glycosaminoglycans in Sprague-Dawley rat aorta, Journal of Nutritional Biochemistry 17(2):109-116, 2006.
- Kalea A.Z., Lamari F.N., Theocharis A.D., Schuschke D.A., Karamanos N.K., Klimis-Zacas D.J. Heparan Sulfate Glycosaminoglycan Composition and Structure is affected by Dietary Manganese (Mn) in the Sprague-Dawley Rat Aorta, Biometals, 19(5):535-46, 2006.
- Kalea A.Z., Schuschke D, Harris P.D. & Klimis-Zacas, D. Cyclo-oxygenase inhibition restores the attenuated vasodilation in manganese deficiency, Journal of Nutrition, 136(9):2302-7, 2006.
- Papandreou, M.A., Efthimiopoulos, S., Cordopatis, P., Klimis-Zacas, D., Margariti, M., & Lamari, F.N. Inhibitory activity on amyloid-beta-protein aggregation and antioxidant properties of blueberry extract, Review of International Pharmacology and Pharmacokinetics, 20(2):105-107, 2006.
- Klimis-Zacas D.J., Kalea A.Z., Yannakoulia M, Matalas A-L, Vassilakou T, Papoutsakis-Tsarouha C, Yiannakouris N, Polychronopoulos E & Passos M. Dietary Intakes of Greek Urban Adolescents do not meet the Recommendations, Nutrition Research, 27:18-26, 2007.
- 1. D. Klimis-Zacas and I. Wolinsky. Nutritional Concerns of Women, 2nd edition CRC Press Inc., Boca Raton, Fl., 2003
- 2. D. Klimis-Zacas, Annual Editions: Nutrition 2001/2002, McGraw-Hill/Dushkin, 2001
- 3. D. Klimis-Zacas, Annual Editions: Nutrition 2002/2003, McGraw-Hill/Dushkin, 2002
- 4. D. Klimis-Zacas, Annual Editions: Nutrition 2003/2004, McGraw-Hill/Dushkin, 2003
- 5. D. Klimis-Zacas, Annual Editions: Nutrition 2004/2005, McGraw-Hill/Dushkin, 2004
- M.Yiannakoulia, N. Yiannakouris, S. Bluher, A-L Matalas, D.Klimis-Zacas and C.S. Mantzoros. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentration in healthy humans, Journal of Clinical Endocrinology and Metabolism, 88:1730-6, 2003.
- M. Yiannakoulia, A. Matalas, N. Yiannakouris, C. Papoutsakis, M. Passos and D. Klimis-Zacas. Disordered Eating Attitudes: An Emerging Health Problem Among Mediterranean Adolescents, Journal of Eating Disorders 9(2) 126-133, 2004.
- C. Norton, A. Z. Kalea, P. D. Harris and D. Klimis-Zacas. Wild blueberry rich diets affect the contractile machinery of the vascular smooth muscle in the Sprague-Dawley rat, Journal of Medicinal Food 8:8-13, 2005.
- A.Z. Kalea, Harris P.D.and D. Klimis-Zacas. Dietary manganese suppresses α-1 adrenergic receptor-mediated vascular contraction, Journal of Nutritional Biochemistry 16:44-49, 2005.
|
Progress 10/01/05 to 09/30/06
Outputs
We examined the effect of dietary manganese (Mn) on the vasodilation pathways of rat aorta. Weanling male Sprague-Dawley rats were fed either a Mn Deficient (MnD) or Mn Adequate/Control diet (MnA)(<1 and 12ppm Mn respectively) for 14wks. Aortas were excised and 3mm rings were prepared. After equilibration and preconditioning we investigated endothelium-dependent (ED) vasodilation induced by Acetylcholine (Ach, 10-8 to 3x10-6mol/L) in aortic rings precontracted with L-Phenylephrine (L-Phe, 10-6mol/L). Seven concentrations of Ach were used in the presence or absence of inhibitors of nitric oxide (NO) synthase (L-NMMA) and cyclo-oxygenase (COX) (MFA). L-Arginine (L-Arg, substrate for NO) was added to detect increases in vasodilation. After precontraction, eight doses of sodium nitroprusside (SNP, 10-8 to 10-5mol/L) were added to assess endothelium-independent vasodilation. The percent of relaxation to the initial contraction was used to determine vessel sensitivity (pD2)
to agonists. A two-way ANOVA test revealed a decreased Ach-induced and SNP-induced vasodilation in MnD aortas when compared to MnA (p≤0.05). Vessel sensitivity of MnD and MnA aortas to Ach was similar. Addition of L-Arg had no effect on NO-mediated vasodilation in the diet groups. NOS-inhibition blunted ED-vasodilation to the same degree for both diet groups. COX-inhibition enhanced both Ach-induced and SNP-induced vasodilation of MnD rings when compared to MnA (p≤0.05). Thus, Mn inhibits the synthesis or activity of a prostanoid-derived vasoconstrictor, which seems to be present at basal and at stimulated levels. This effect is independent of membrane-related events. Our results provide further information on the critical role of Mn on vasomotor tone.
Impacts
Cardiovascular Disease (CVD) still remains the leading cause of death in the adult US population. One of the trace elements implicated in the development of CVD is manganese. Our results demonstrate for the first time that dietary manganese affects the biomechanical properties of blood vessels and helps regulate vascular tone with implications to blood pressure regulation. After studying the effect of manganese on the vasodilation pathways of rat aorta, we concluded that the presence of manganese in the diet helps vessels relax by inhibiting the synthesis or activity of a vasoconstrictor. This may have implications on high blood pressure and Cardiovascular Disease.
Publications
- Kalea A.Z., Schuschke D, Harris P.D. & Klimis-Zacas, D. Cyclo-oxygenase inhibition restores the attenuated vasodilation in manganese deficiency. Journal of Nutrition, 136(9):2302-7, 2006
- Dorothy Klimis-Zacas, Annual Editions in Nutrition 06/07, The McGraw-Hill Companies, 2006 Kalea A.Z., Lamari F.N., Theocharis A.D., Cordopatis P., Schuschke D.A., Karamanos N.K., Klimis-Zacas D.J. Wild blueberry (Vaccinium angustifolium) consumption affects the composition and structure of glycosaminoglycans in Sprague-Dawley rat aorta. Journal of Nutritional Biochemistry. 17(2): 109-116, 2006
- Kalea A.Z., Lamari F.N., Theocharis A.D., Schuschke D.A., Karamanos N.K., Klimis-Zacas D.J. Heparan sulfate Glycosaminoglycan Composition and structure is affected by Dietary Manganese (Mn) in the Sprague-Dawley Rat Aorta Biometals, 19(5):535-46, 2006
- Klimis-Zacas D.J., Kalea A.Z., Yannakoulia M, Matalas A-L, Vassilakou T, Papoutsakis-Tsarouha C, Yiannakouris N, Polychronopoulos E & Passos M. Dietary Intake and Nutritional Status of Greek adolescents. Nutrition Research, 2007 (accepted for publication)
- Kalea A.Z., Lamari F., Theocharis A.D., Karamanos N.K., Klimis-Zacas, D. Dietary blueberries affect the composition and structure of rat aortic extracellular matrix, FASEB J. 19(4): A451, 2005
- Kalea A.Z., Schuschke D, Harris P.D. & Klimis-Zacas, D. Cyclooxygenase inhibition restores endothelium-dependent vasodilation in manganese deficiency FASEB J. 20(4):A465.10, 2006
- Clark K., Kalea A.Z., Schuschke D, Harris P.D. & Klimis-Zacas, D. Effect of dietary blueberries on endothelium-dependent vasodilation in spontaneously hypertensive rats , Late breaking abstracts, FASEB J., 2006 Papandreou M.A., Efthimiopulos S., Cordopatis P., Klimis-Zacas D., Margariti M. & Lamari F.N. Inhibitory activity on amyloid-beta protein aggregation and antioxidant properties of blueberry extracts, Hellenic Society of Pharmacology Proceedings, March 2006
- Wild blueberries affect the composition of the extracellular matrix in rat aorta, Federation of American Societies for Experimental Biology, San Diego, CA, April 2005
- Cyclooxygenase inhibition restores endothelium-dependent vasodilation in manganese deficiency, Federation of American Societies for Experimental Biology, San Francisco, California, April 2006
- Effect of dietary blueberries on endothelium-dependent vasodilation in spontaneously hypertensive rats, Federation of American Societies for Experimental Biology, San Francisco, California, April 2006
|