Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis

Abstract

Atherosclerosis (AS) is a chronic inflammatory disease and leading cause of cardiovascular diseases. The progression of AS is a multi-step process leading to high morbidity and mortality. Hyperglycemia, dyslipidemia, advanced glycation end products (AGEs), inflammation and insulin resistance which strictly involved in diabetes are closely related to the pathogenesis of AS. A growing number of studies have linked AGEs to AS. As one of the risk factors of cardiac metabolic diseases, dysfunction of VSMCs plays an important role in AS pathogenesis. AGEs are increased in diabetes, participate in the occurrence and progression of AS through multiple molecular mechanisms of vascular cell injury. As the main functional cells of vascular, vascular smooth muscle cells (VSMCs) play different roles in each stage of atherosclerotic lesions. The interaction between AGEs and receptor for AGEs (RAGE) accelerates AS by affecting the proliferation and migration of VSMCs. In addition, increasing researches have reported that AGEs promote osteogenic transformation and macrophage-like transformation of VSMCs, and affect the progression of AS through other aspects such as autophagy and cell cycle. In this review, we summarize the effect of AGEs on VSMCs in atherosclerotic plaque development and progression. We also discuss the AGEs that link AS and diabetes mellitus, including oxidative stress, inflammation, RAGE ligands, small noncoding RNAs.

The possible role of nuclear factor erythroid‐2‐related factor 2 activators in the management of Covid‐19

“…[129][130][131][132][133] AGEs are typically produced during the aging process, though excessive production of AGEs is associated with vascular inflammation, atherosclerosis, OS, insulin resistance, and diabetes. [134] AGEs promote the release of pro-inflammatory cytokines in diabetes and other metabolic disorders. [134] AGEs induce the propagation of OS and inflammatory disorders in diabetes with subsequent activation of the Nrf2 pathway to reduce OS and/or inflammatory reactions.…”

“…[134] AGEs promote the release of pro-inflammatory cytokines in diabetes and other metabolic disorders. [134] AGEs induce the propagation of OS and inflammatory disorders in diabetes with subsequent activation of the Nrf2 pathway to reduce OS and/or inflammatory reactions. [135] Indeed, Nrf2/HO-1/NQO1 axis is highly activated in the endothelial cells subjected to AGEs activators to provide an adaptive response against OS and/or inflammatory reactions in diabetes.…”

“…[ 134 ] AGEs promote the release of pro‐inflammatory cytokines in diabetes and other metabolic disorders. [ 134 ] AGEs induce the propagation of OS and inflammatory disorders in diabetes with subsequent activation of the Nrf2 pathway to reduce OS and/or inflammatory reactions. [ 135 ]…”

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“…Given that AGEs are able to induce the proliferation of various types of cells [19,[25][26][27], we speculated that increased AGEs could contribute to the excessive proliferation of epidermal keratinocytes in psoriasis. To verify this, we first examined the growth of NHKs treated with BSA-AGEs via CCK8 assay and resazurin-reduction assay.…”

Insulin resistance in ischemic stroke: Mechanisms and therapeutic approaches

“…Hyperinsulinemia, which is caused by IR, is a potential growth factor that promotes its growth through the MAPK pathway, which catalyzes the phosphorylation of transcription factors that stimulate VSMCs growth, proliferation, and differentiation ( 52 ). It has been demonstrated that IR-related inflammation can also promote the development of VSMCs ( 53 ). C-peptide, produced by the cleavage of proinsulin in the β-cell.…”