N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function
العنوان: | N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function |
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المؤلفون: | Shane Duclos, Sugata Hazra, Andrew L. Sochacki, Svetlana N. Bozack, Kelly M. McSorley, Matthew S. Faber, Dennis L. Guberski, Todd A. Lydic, Sergio Li Calzi, Madalina Opreanu, Maria Tikhonenko, Maria B. Grant, Julia V. Busik, Gavin E. Reid |
المصدر: | PLoS ONE, Vol 8, Iss 1, p e55177 (2013) PLoS ONE |
بيانات النشر: | Public Library of Science (PLoS), 2013. |
سنة النشر: | 2013 |
مصطلحات موضوعية: | Interleukin-1beta, lcsh:Medicine, Cardiovascular, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Bone Marrow, lcsh:Science, 0303 health sciences, Multidisciplinary, Stem Cells, Diabetic retinopathy, Intercellular Adhesion Molecule-1, 3. Good health, medicine.anatomical_structure, Sphingomyelin Phosphodiesterase, Docosahexaenoic acid, cardiovascular system, Cytokines, Medicine, Retinal Disorders, medicine.symptom, Acid sphingomyelinase, medicine.drug, Research Article, medicine.medical_specialty, Docosahexaenoic Acids, Clinical Research Design, Blotting, Western, Immunology, 030209 endocrinology & metabolism, Inflammation, Biology, Endothelial progenitor cell, 03 medical and health sciences, Vascular Biology, Internal medicine, medicine, Animals, Animal Models of Disease, Progenitor cell, 030304 developmental biology, Diabetic Endocrinology, Retina, Diabetic Retinopathy, Interleukin-6, lcsh:R, Endothelial Cells, Retinal Vessels, Retinal, Diabetes Mellitus Type 2, medicine.disease, Rats, Ophthalmology, chemistry, Diabetes Mellitus, Type 2, Immune System, lcsh:Q |
الوصف: | Objective The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs). We propose that n-3 polyunsaturated fatty acid (PUFA) deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM) and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs. Research Design and Methods Type 2 diabetic rats on control or docosahexaenoic acid (DHA)-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL)-1β, IL-6, intracellular adhesion molecule (ICAM)-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined. Results DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation. Conclusions In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function. |
اللغة: | English |
تدمد: | 1932-6203 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6865999d81e046cef0da24017ba8c53e http://europepmc.org/articles/PMC3558503?pdf=render |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....6865999d81e046cef0da24017ba8c53e |
قاعدة البيانات: | OpenAIRE |
تدمد: | 19326203 |
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