Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease
Obesity and non-alcoholic fatty liver disease (NAFLD) are on the rise world-wide; despite fervent advocacy for healthier diets and enhanced physical activity, these disorders persist unabated and, long-term, are major causes of morbidity and mortality. Numerous fundamental biochemical and molecular...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.937071/full |
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| author | Lakshmi Arivazhagan Raquel López-Díez Alexander Shekhtman Ravichandran Ramasamy Ann Marie Schmidt |
| author_facet | Lakshmi Arivazhagan Raquel López-Díez Alexander Shekhtman Ravichandran Ramasamy Ann Marie Schmidt |
| author_sort | Lakshmi Arivazhagan |
| collection | DOAJ |
| description | Obesity and non-alcoholic fatty liver disease (NAFLD) are on the rise world-wide; despite fervent advocacy for healthier diets and enhanced physical activity, these disorders persist unabated and, long-term, are major causes of morbidity and mortality. Numerous fundamental biochemical and molecular pathways participate in these events at incipient, mid- and advanced stages during atherogenesis and impaired regression of established atherosclerosis. It is proposed that upon the consumption of high fat/high sugar diets, the production of receptor for advanced glycation end products (RAGE) ligands, advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs), contribute to the development of foam cells, endothelial injury, vascular inflammation, and, ultimately, atherosclerosis and its consequences. RAGE/Diaphanous-1 (DIAPH1) increases macrophage foam cell formation; decreases cholesterol efflux and causes foam cells to produce and release damage associated molecular patterns (DAMPs) molecules, which are also ligands of RAGE. DAMPs stimulate upregulation of Interferon Regulatory Factor 7 (IRF7) in macrophages, which exacerbates vascular inflammation and further perturbs cholesterol metabolism. Obesity and NAFLD, characterized by the upregulation of AGEs, ALEs and DAMPs in the target tissues, contribute to insulin resistance, hyperglycemia and type two diabetes. Once in motion, a vicious cycle of RAGE ligand production and exacerbation of RAGE/DIAPH1 signaling ensues, which, if left unchecked, augments cardiometabolic disease and its consequences. This Review focuses on RAGE/DIAPH1 and its role in perturbation of metabolism and processes that converge to augur cardiovascular disease. |
| first_indexed | 2024-12-12T07:28:07Z |
| format | Article |
| id | doaj.art-6f532574044947eba9d0def032933819 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-12T07:28:07Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-6f532574044947eba9d0def0329338192022-12-22T00:33:06ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.937071937071Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic DiseaseLakshmi Arivazhagan0Raquel López-Díez1Alexander Shekhtman2Ravichandran Ramasamy3Ann Marie Schmidt4Diabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY, United StatesDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY, United StatesDepartment of Chemistry, The State University of New York at Albany, Albany, NY, United StatesDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY, United StatesDiabetes Research Program, Department of Medicine, New York University Grossman School of Medicine, New York, NY, United StatesObesity and non-alcoholic fatty liver disease (NAFLD) are on the rise world-wide; despite fervent advocacy for healthier diets and enhanced physical activity, these disorders persist unabated and, long-term, are major causes of morbidity and mortality. Numerous fundamental biochemical and molecular pathways participate in these events at incipient, mid- and advanced stages during atherogenesis and impaired regression of established atherosclerosis. It is proposed that upon the consumption of high fat/high sugar diets, the production of receptor for advanced glycation end products (RAGE) ligands, advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs), contribute to the development of foam cells, endothelial injury, vascular inflammation, and, ultimately, atherosclerosis and its consequences. RAGE/Diaphanous-1 (DIAPH1) increases macrophage foam cell formation; decreases cholesterol efflux and causes foam cells to produce and release damage associated molecular patterns (DAMPs) molecules, which are also ligands of RAGE. DAMPs stimulate upregulation of Interferon Regulatory Factor 7 (IRF7) in macrophages, which exacerbates vascular inflammation and further perturbs cholesterol metabolism. Obesity and NAFLD, characterized by the upregulation of AGEs, ALEs and DAMPs in the target tissues, contribute to insulin resistance, hyperglycemia and type two diabetes. Once in motion, a vicious cycle of RAGE ligand production and exacerbation of RAGE/DIAPH1 signaling ensues, which, if left unchecked, augments cardiometabolic disease and its consequences. This Review focuses on RAGE/DIAPH1 and its role in perturbation of metabolism and processes that converge to augur cardiovascular disease.https://www.frontiersin.org/articles/10.3389/fcvm.2022.937071/fullRAGE axisglycationlipoxidationcardiometabolic diseaseobesitynon-alcoholic fatty liver disease |
| spellingShingle | Lakshmi Arivazhagan Raquel López-Díez Alexander Shekhtman Ravichandran Ramasamy Ann Marie Schmidt Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease Frontiers in Cardiovascular Medicine RAGE axis glycation lipoxidation cardiometabolic disease obesity non-alcoholic fatty liver disease |
| title | Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease |
| title_full | Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease |
| title_fullStr | Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease |
| title_full_unstemmed | Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease |
| title_short | Glycation and a Spark of ALEs (Advanced Lipoxidation End Products) – Igniting RAGE/Diaphanous-1 and Cardiometabolic Disease |
| title_sort | glycation and a spark of ales advanced lipoxidation end products igniting rage diaphanous 1 and cardiometabolic disease |
| topic | RAGE axis glycation lipoxidation cardiometabolic disease obesity non-alcoholic fatty liver disease |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.937071/full |
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