Role of AGE-RAGE Pathway in the Pathogenesis of Cardiovascular Disease as a Complication of Diabetes Mellitus

Bekheit, Sarah Ouda; El-Awady, El-Sayed E.; Kolieb, Eman; Khodeer, Dina M.

doi:10.21608/rpbs.2024.322374.1326

Role of AGE-RAGE Pathway in the Pathogenesis of Cardiovascular Disease as a Complication of Diabetes Mellitus

Document Type : Mini-reviews

Authors

¹ El-Sheikh Zuweid Health Administration, Health Affairs Directorate, North Sinai 45613, Egypt

² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt

³ Department of Medical Physiology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt

10.21608/rpbs.2024.322374.1326

Abstract

Diabetes mellitus (DM) is marked by hyperglycemia. An association has been discovered between extended durations of elevated blood glucose levels and a higher occurrence of both micro-and macrovascular diseases in individuals with diabetes. This correlation is present even after achieving glycemic control, indicating an inherent process known as "metabolic memory." Advanced glycation end products (AGEs) are proteins that have undergone glycation and are believed to have a role in metabolic memory. They are produced more in the presence of excessive blood glucose levels and have a sluggish turnover rate. Increased levels of AGEs may cause aberrant cross-linking of proteins in both the extracellular and intracellular spaces, resulting in disruptions in their typical arrangement and function. In addition, the activation of AGE receptor may initiate intricate signalling pathways that result in heightened oxidative stress, inflammation, elevated calcium deposition, and enhanced vascular smooth muscle cell death. All of these variables together lead to the advancement of atherosclerosis. AGEs are likely to substantially impact the increasing prevalence of cardiovascular disease (CVD). Furthermore, it is crucial to explore novel treatment strategies that specifically target AGEs and associated pathways in order to mitigate and treat CVD in individuals with diabetes metabolic disorders, with the goal of improving clinical results.

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