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. 2016 Jul 19;11(7):e0159175.
doi: 10.1371/journal.pone.0159175. eCollection 2016.

The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients

Ma Etzabel Villegas-Rodríguez  1 , Jaime Uribarri  2 , Sergio E Solorio-Meza  3 , Martha E Fajardo-Araujo  1 , Weijing Cai  2 , Sofía Torres-Graciano  1 , Rubén Rangel-Salazar  1 , Kazimierz Wrobel  4 , Ma Eugenia Garay-Sevilla  1
Affiliations

The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients

Ma Etzabel Villegas-Rodríguez et al. PLoS One. .

Abstract

Aim: The purpose of the study was the simultaneous measurement of all the different components of the AGE-RAGE axis as well as several non-invasive markers of cardiovascular disease (CVD) in a cohort of newly diagnosed diabetic patients.

Materials and methods: In 80 newly diagnosed diabetic patients we measured serum carboxymethyllysine (CML), soluble RAGE (sRAGE) and peripheral mononuclear (PMNC) RAGE and AGER1 mRNA together with ICAM-1, VCAM-1, and malondialdehyde (MDA). We also assessed cardiovascular function by measurement of flow-mediated vasodilation (FMD), intima-media thickness (IMT) and arterial stiffness. Univariant correlation analysis was used to determine correlation between the variables in the study and multiple regression analysis was used to examine the association between the AGE-RAGE axis components and FMD, IMT and arterial stiffness.

Results: Serum CML correlated positively with sRAGE, PMNC RAGE, HOMA-IR, ICAM-1, VCAM-1 and MDA, but inversely with PMNC AGER1. sRAGE and RAGE was positively correlated with AGER; IMT was positively correlated with HOMA-IR, ICAM-1, VCAM-1, MDA, and sRAGE and arterial stiffness had correlation with HOMA-IR, ICAM-1, VCAM-1, MDA, CML, sRAGE, AGER1 and RAGE. In multivariate analysis we found a significant relationship between CML with PMNC RAGE, HOMA-IR; sRAGE with VCAM-1 and MDA; PMNC RAGE with PMNC AGER1and CML; PMNC AGER1 with PMNC RAGE; FMD with sRAGE, CML and HbA1c; IMT with sRAGE, and arterial stiffness with sRAGE, sCML and AGER1.

Conclusions: We found significant and strong associations between the different components of the AGE-RAGE axis and also found significant association between AGE-RAGE axis markers, especially sRAGE with several noninvasive markers of cardiovascular disease risk. sRAGE, an easily measured parameter in blood, may potentially be used as a surrogate marker of AGEs-RAGE in patients with diabetes.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
(A) Show the correlation between sRAGE with CML. (B) Expression of RAGE with CML. (C) Expression of AGER1 with CML and (D) Expression of RAGE with sRAGE
Fig 2
Fig 2
(A) Show the correlation between flow-mediated vasodilation with expression of AGER1. (B) Intima-media thickness with sRAGE and (C) Arterial Stiffness with Expression of RAGE.
See this image and copyright information in PMC

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