Association between Advanced Glycation End Products, Soluble RAGE Receptor, and Endothelium Dysfunction, Evaluated by Circulating Endothelial Cells and Endothelial Progenitor Cells in Patients with Mild and Resistant Hypertension.

Bogna Gryszczyńska,Magdalena Budzyń,Mariusz Kaczmarek,Beata Begier-Krasińska,Alicja Bukowska,Maciej Boruczkowski,Maria Iskra,Magdalena Paulina Kasprzak,Angelika Osińska

doi:10.3390/ijms20163942

Abstract

The aim of the present study was to evaluate advanced glycation end products (AGEs) and soluble form of receptor RAGE (sRAGE) concentrations as well as the AGEs/sRAGE ratio in mild (MH) and resistant (RH) hypertensive patients in comparison with normotensive individuals. We also evaluated the association between AGEs, sRAGE as well as AGEs/sRAGE ratio and circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs). The MH group consisted of 30 patients, whereas 30 patients were classified for the RH group. The control group (C) included 25 normotensive volunteers. AGEs and sRAGE were measured using enzyme-linked-immunosorbent assay (ELISA). The multicolor flow cytometry was used for analysis of CECs and CEPCs. Significantly higher levels of AGEs in RH cohort were observed as compared to C cohort. Furthermore, significantly lower sRAGE levels as well as a higher AGEs/sRAGE ratio were observed between MH and RH cohorts. Significant correlations were found in the MH cohort for sRAGE and CECs, and CEPCs. The elevation of AGEs levels suggests that oxidative modification of proteins occurs in hypertension pathogenesis. The decrease in sRAGE levels and elevation of the AGEs/sRAGE ratio in MH and RH groups may suggest that hypertensive patients are less protected against the side effects of AGEs as a consequence of an insufficient competitive role of sRAGE against the AGEs-RAGE axis. Finally, it may be concluded that the level of AGEs may be an independent predictor of the condition and function of the endothelium. Furthermore, sRAGE may be classified as a potential biomarker of inflammation and endothelium dysfunction.

Highlights

Hypertension is one of the most complex and chronic diseases in the world
We demonstrated that the advanced glycation end products (AGEs)/soluble form of receptor RAGE (sRAGE) ratio is negatively correlated with the number of circulating endothelial progenitor cells (CEPCs) in the Mild hypertension (MH) group
The analysis of various parameters/factors confirmed that increased oxidative stress and inflammation are involved in vascular damage in pathogenesis of hypertension

Summary

Introduction

Hypertension is one of the most complex and chronic diseases in the world. Patients with hypertension have a significant risk of developing cardiovascular and renal diseases [1,2]. Stages of hypertension have been identified and are applied in clinical diagnosis [3,4,5]. Mild hypertension (MH), known as grade 1 hypertension, is defined as systolic blood pressure between 140–159 mmHg and diastolic blood pressure between 90–99 mmHg [6]. Resistant hypertension (RH) is defined as blood pressure measurements that remain above 140/90 mmHg despite use of varying classes of antihypertensive medications, including a diuretic. Resistant hypertensive patients have a higher risk of end-organ consequences, including heart failure, stroke, ischemic heart disease, and renal failure [3,4,6]

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