Receptor for Advanced Glycation End Products (RAGE) and Mechanisms and Therapeutic Opportunities in Diabetes and Cardiovascular Disease: Insights From Human Subjects and Animal Models

Egaña-Gorroño, Lander; López‐Díez, Raquel; Yepuri, Gautham; Ramirez, Lisa; Reverdatto, Sergey; Gugger, Paul F.; Shekhtman, Alexander; Ramasamy, Ravichandran; Schmidt, Ann Marie

doi:10.3389/fcvm.2020.00037

Cited by 143 publications

(131 citation statements)

References 134 publications

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“…Receptor for advanced glycation end products (receptor for AGE, RAGE) and its soluble form, sRAGE, are involved in diabetes mellitus (DM)-related diseases [ 1 , 2 ]. RAGE is a membrane-bound receptor expressed at low levels in most human tissues, but with the lungs being the richest ones [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…sRAGE is composed of the endogenously secretory form (esRAGE) and the membrane-cleaved form (cRAGE). The first is considered the real decoy receptor, the second a surrogate marker of inflammation [ 1 , 2 ], but both can block ligand from binding to membrane RAGE. Engagement of RAGE increases its expression, activates inflammation, downregulates esRAGE, and promotes RAGE cleavage into cRAGE.…”

Section: Introductionmentioning

confidence: 99%

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Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers

Dozio

Sitzia

Pistelli

et al. 2020

JCM

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The receptor for advanced glycation end products (RAGE), a well-known player of diabetes mellitus (DM)-related morbidities, was supposed to be involved in coronavirus disease-19 (COVID-19), but no data exist about COVID-19, DM, and the soluble RAGE (sRAGE) forms. We quantified total sRAGE and its forms, the endogenously secretory esRAGE and the membrane-cleaved cRAGE, in COVID-19 patients with and without DM and in healthy individuals to explore how COVID-19 may affect these molecules and their potential role as biomarkers. Circulating sRAGE and esRAGE were quantified by enzyme-linked-immunosorbent assays. cRAGE was obtained by subtracting esRAGE from total sRAGE. sRAGE, esRAGE, cRAGE, and the cRAGE/esRAGE ratio did not differ between DM and non-DM patients and had the same trend when compared to healthy individuals. Levels of total sRAGE, cRAGE, and cRAGE/esRAGE ratio were upregulated, while esRAGE was downregulated. The lack of difference between DM and non-DM COVID-19 patients in the levels of sRAGE and its forms supports the hypothesis that in COVID-19 the RAGE system is modulated regardless of glycemic control. Identifying how sRAGE and its forms associate to COVID-19 prognosis and the potential of RAGE as a therapeutic target to control inflammatory burden seem of relevance to help treatment of COVID-19.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers

Dozio

Sitzia

Pistelli

et al. 2020

JCM

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show abstract

“…Previous studies have shown that RAGE is expressed in both nondiabetic and diabetic atherosclerotic lesions in human subjects, levels of sRAGE have been extensively studied in humans subject to test associations of RAGE pathway to diabetes, CVD and thrombotic disorders [4]. We have demonstrated that sRAGE levels were markedly associated in diabetes with and without microvascular complications and in inflammatory diseases [5][6][7].…”

mentioning

confidence: 77%

RAGE receptor: May be a potential inflammatory mediator for SARS-COV-2 infection?

Kerkeni

Gharbi

2020

Medical Hypotheses

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Knowledge of the pathophysiology of SARS-COV-2 has provided a strong stimulus to further our understanding of the viral infection and its associated diseases. No data is available regarding RAGE receptor, and its relationships with SARS-COV-2 infection. Receptor for advanced glycation end products (RAGE), a 35 KDa protein from immunoglobulin superfamily, is a pro-inflammatory pattern recognition receptor (PRRs) that has been related to many in

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“…It has been reported that sRAGE has a negative cross-sectional correlation with cardiovascular complications in diabetic, prediabetes, and non-diabetic individuals [4,6,18]. Patients with a lower number of sRAGE have a higher cardiovascular mortality rate [19]. The higher rate of sRAGE is associated with less incidence of arterial fibrillation after catheter ablation of diabetic patients.…”

Section: Possible Molecular Mechanismsmentioning

confidence: 99%

The cardiovascular complications of diabetes: a striking link through protein glycation

Ahmad

Farah

Al-Qirim

2020

Romanian Journal of Internal Medicine

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Diabetes mellitus is a predominant cause of mortality and morbidity worldwide. One of its serious health problems is cardiovascular complications. Advanced glycation end products (AGEs) are a group of heterogeneous toxic oxidant compounds that are formed after a nonenzymatic reaction between monosaccharides and free amino groups of proteins, compound lipids, and nucleic acids. AGE interacts with various types of cells through a receptor for AGE (RAGE). The interaction between AGE and RAGE is responsible for a cascade of inflammation, oxidative stress, and disruption of calcium homeostasis in cardiac cells of diabetic patients. There is striking evidence that the AGE/RAGE axis with its consequences on inflammation and oxidative stress plays a major role in the development of cardiovascular complications. Therefore, considering AGE as a therapeutic target with foreseeable results would be a wise direction for future research. Interestingly, several studies on nutraceutical, pharmaceutical, and natural products have begun to reveal promising therapeutic results, and this could lead to better health outcomes for many diabetic patients worldwide. This article discusses the current literature addressing the connection between protein glycation and diabetes cardiovascular complications and suggests future avenues of research.

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Receptor for Advanced Glycation End Products (RAGE) and Mechanisms and Therapeutic Opportunities in Diabetes and Cardiovascular Disease: Insights From Human Subjects and Animal Models

Cited by 143 publications

References 134 publications

Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers

Soluble Receptor for Advanced Glycation End Products and Its Forms in COVID-19 Patients with and without Diabetes Mellitus: A Pilot Study on Their Role as Disease Biomarkers

RAGE receptor: May be a potential inflammatory mediator for SARS-COV-2 infection?

The cardiovascular complications of diabetes: a striking link through protein glycation

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