Mitochondrial Alterations and Enhanced Human Leukocyte/Endothelial Cell Interactions in Type 1 Diabetes

Francesca Iannantuoni,Zaida Abad-Jiménez,Pedro Díaz-Pozo,Sandra López-Domènech,Carlos Morillas,Milagros Rocha,Víctor M Víctor,Aranzazu M De Marañon,Francisco Canet

doi:10.3390/jcm9072155

Abstract

Type 1 diabetes has been associated with oxidative stress. This study evaluates the rates of oxidative stress, mitochondrial function, leukocyte–endothelium interactions and adhesion molecules in type 1 diabetic patients. The study population consisted of 52 diabetic patients and 46 body-composition and age-matched controls. We assessed anthropometric and metabolic parameters, oxidative stress and mitochondrial function by evaluating reactive oxygen species (ROS) production, mitochondrial ROS production, mitochondrial membrane potential and superoxide dismutase (SOD) and catalase (CAT) expression in polymorphonuclear leukocytes from type 1 diabetic patients. In addition, we evaluated interactions between leukocytes and human umbilical vein endothelial cells (HUVEC), and serum expression of adhesion molecules (P-selectin, VCAM-1 and ICAM-1), proinflammatory cytokines (IL-6 and TNFα) and myeloperoxidase (MPO). HbA1C and glucose levels were higher in diabetic patients than in control subjects, as expected. Mitochondrial function was altered and leukocyte–endothelium interactions were enhanced in diabetic patients, which was evident in the increase in total and mitochondrial ROS production, higher mitochondrial membrane potential, enhanced leukocyte rolling and adhesion, and decreased rolling velocity. Furthermore, we observed an increase in levels of adhesion molecules P-selectin, VCAM-1, and ICAM-1 in these subjects. In addition, type 1 diabetic patients exhibited an increase in proinflammatory mediators TNFα and MPO, and a decreased expression of SOD. The enhancement of leukocyte–endothelium interactions and proinflammatory markers correlated with glucose and HbA1Clevels. Mitochondrial alteration, oxidative stress, and enhanced leukocyte–endothelium interactions are features of type 1 diabetes and may be related to cardiovascular implications.

Highlights

Mitochondrial dysfunction and cardiovascular events have been previously related to metabolic diseases such as obesity and diabetes
Impaired mitochondrial energetics and oxidative damage have been implicated in cardiac dysfunction in obesity and diabetes [1,2,3], and a disruption of physiological reactive oxygen species (ROS) homeostasis may lead to the impairment of β-cell function [4]
The following comorbidities were reported among the type 1 diabetic group: 15 patients were affected by retinopathy, 3 by nephropathy and 3 by neuropathy

Summary

Introduction

Mitochondrial dysfunction and cardiovascular events have been previously related to metabolic diseases such as obesity and diabetes. Impaired mitochondrial energetics and oxidative damage have been implicated in cardiac dysfunction in obesity and diabetes [1,2,3], and a disruption of physiological reactive oxygen species (ROS) homeostasis may lead to the impairment of β-cell function [4]. It has been estimated that the relative risk of CVDs in these patients is 10 times higher than in non-diabetics [7]. In this sense, it is important to highlight that one of the key factors in the development of CVDs is atherosclerosis. The longer duration of type 1 diabetes can promote CVDs through different pathophysiological pathways [7,12,13]

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