Copyright
©The Author(s) 2023.
World J Diabetes. Aug 15, 2023; 14(8): 1146-1162
Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1146
Published online Aug 15, 2023. doi: 10.4239/wjd.v14.i8.1146
Figure 2 Advanced glycation end product-mediated diabetic cardiovascular complications.
AGEs mediate their pathological effects at the cellular and extracellular level by multiple pathways. At the cellular level, they activate signaling cascades via RAGE and initiate a complex series of intracellular signaling leading to reactive oxygen species generation, oxidative stress development, inflammation, adhesion molecule expression, endothelin-1, plasmin activator inhibitor 1, tumor necrosis factor alpha, chemoattraction of inflammatory cells, smooth muscle and fibroblast proliferation, autophagy, and apoptosis. AGE–RAGE interaction modulate the cellular properties through stimulation of signaling molecules such as ERK 1/2, p21RAS, MAPK, NF-B, cdc42/rac, and Janus kinase/STAT and adversely affects the cardiovascular health in diabetes. AGEs also causes covalent modifications and crosslinking of serum and ECM proteins, altering their structure, stability, and functions. Modification of ECM proteins and cross-linking interferes with cell–matrix and matrix–matrix interactions, affecting the matrix–cell signaling and leading to profibrotic action, decreased elasticity, increased stiffness, narrowing of vessels, and other hallmarks of atherosclerosis. VCAM1: Vascular cell adhesion molecules; JAK: Janus kinase; RAGE: Receptor for advanced glycation end products; NADPH: Nicotinamide adenine dinucleotide phosphate oxidase; NF-κB: Nuclear factor-B; AGEs: Advanced glycation end products; MAPK: Mitogen-activated protein kinase; ROS: Reactive oxygen species; TNF-α: Tumor necrosis factor ; ERK: Extracellular signal-regulated kinase; LDL: Low-density lipoprotein; ECM: Extracellular matrix.
- Citation: Bansal S, Burman A, Tripathi AK. Advanced glycation end products: Key mediator and therapeutic target of cardiovascular complications in diabetes. World J Diabetes 2023; 14(8): 1146-1162
- URL: https://www.wjgnet.com/1948-9358/full/v14/i8/1146.htm
- DOI: https://dx.doi.org/10.4239/wjd.v14.i8.1146