Role of profilin-1 in vasculopathy induced by advanced glycation end products (AGEs) |
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| Affiliation: | 1. Department of Geriatric Cardiology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China;2. Department of Cardiology, The First Affiliated Hospital of Shangdong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Jinan, Shandong 250014, China;1. Department of Health Policy and Management, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America;2. Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, United States of America;3. Department of Medicine and Pharmacology, School of Medicine, Tulane University, New Orleans, LA, United States of America;4. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America;1. AdventHealth Translational Research Institute, Orlando, FL, United States of America;2. Tufts Medical Center, Boston, MA, United States of America;3. The University of Nebraska Medical Center and Omaha Veterans Affairs Medical Center, Omaha, NE, United States of America;4. University of Kansas Medical Center, Kansas City, KS, United States of America;5. Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, and Medical Research Center, University of Oulu and Oulu University Hospital, 90220 Oulu, Finland;6. Department of Pediatric Gastroenterology and Metabolic Diseases, Pediatric Institute, Poznan University of Medical Sciences, 60-572 Poznań, Poland;7. Weill Cornell Medicine, New York, NY, United States of America;8. Stanford University Medical Center, Stanford, CA, United States of America;9. The University of Colorado School of Medicine, Aurora, CO, United States of America;10. The Veterans Affairs Eastern Colorado Health Care System, Aurora, CO, United States of America;11. National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, United States of America;1. School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan;2. Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan;3. Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan;1. Department of Ophthalmology, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, China;2. Department of Key Laboratory, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, China;3. Department of Ophthalmology, Wuxi Clinical College, Nantong University, Wuxi, China;4. Department of Ophthalmology, Wuxi No. 2 People''s Hospital, Nanjing Medical University, Wuxi, China;1. Department of Health Policy and Management, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America;2. Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, United States of America;3. Department of Medicine and Pharmacology, School of Medicine, Tulane University, New Orleans, LA, United States of America;4. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America;1. Department of Endocrinology, Xijing Hospital, Air Force Medical University, Xi''an, Shaanxi, China;2. Nanchang University Queen Mary School, Nanchang, China |
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| Abstract: | AimsTo construct a simple and feasible rat model to mimic diabetic vasculopathy by chronic injection of advanced glycation end products (AGEs) and further determine the role of profilin-1 in vasculopathy in AGE-injection rats.MethodsSprague-Dawley rats were injected with AGEs-BSA (25 mg/kg/day) for 0, 20, 30, 40, and 60 days by caudal vein. Then, the morphological changes in the aorta, heart, and kidney and the expression of profilin-1 were assessed. In cultured endothelial cells, shRNA profilin-1 was used to clarify the role of profilin-1 in AGEs-induced vascular endothelial lesions and inflammatory reactions.ResultsThe aorta, heart, and kidney of the AGE-injection rats had obvious morphological changes. Also, the indicators of vascular remodeling in the aorta significantly increased, accompanied by the increased expression of profilin-1 in the aorta, heart, and kidney and polysaccharide content on the kidney basement membrane. In addition, the protein level of profilin-1 was markedly upregulated in the aorta of AGEs-injected rats and endothelial cells incubated with AGEs. shRNA profilin-1 markedly attenuated the upregulated expression of profilin-1, receptor for AGEs (RAGE), and NF-κB in endothelial cells incubated with AGEs, as well as reduced the high levels of ICAM-1, IL-8, TNF-α, ROS, and apoptosis induced by AGEs.ConclusionsExogenous AGEs can mimic diabetic vasculopathy in vivo to some extent and increase profilin-1 expression in the target organs of diabetic complications. Blockade of profilin-1 attenuates vascular lesions and inflammatory reactions, suggesting its critical role in the metabolic memory mediated by AGEs. |
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