Is Myeloperoxidase a Key Component in the ROS-Induced Vascular Damage Related to Nephropathy in Type 2 Diabetes?

Abstract

It is still unclear whether microvascular complications of type 2 diabetes correlate with leukocyte-endothelium interactions and/or myeloperoxidase (MPO) levels. In the present study, we found that serum levels of glucose, the rate of ROS and MPO concentration were higher in type 2 diabetic patients. Patients with nephropathy (39.6%) presented higher MPO levels that correlate positively with the albumin/creatinine ratio (r = 0.59, p < 0.05). In addition, nephropatic patients showed increased leukocyte-endothelium interactions due to an undermining of polymorphonuclear leukocytes (PMN) rolling velocity and increased rolling flux and adhesion, which was accompanied by a rise in levels of the proinflammatory cytokine tumour necrosis factor alpha (TNFa) and the adhesion molecule E-selectin. Furthermore, MPO levels were positively correlated with PMN rolling flux (r = 0.855, p < 0.01) and adhesion (r = 0.682, p < 0.05). Our results lead to the hypothesis that type 2 diabetes induces oxidative stress and an increase in MPO levels and leukocyte-endothelium interactions, and that these effects correlate with the development of nephropathy.

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

“…Oxidative stress has been related to the pathophysiology of a wide variety of diseases (275,276), including cardiometabolic diseases (hypertension, stroke, diabetes, metabolic syndrome), neurodegenerative disorders (Alzheimer's disease [AD], PD, and others), Duchenne muscular dystrophy, chronic obstructive pulmonary disease (COPD), and cancer.…”

Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients

“…The parallel plate flow chamber in-vitro model has been described in detail elsewhere [26,27]. A Luminex 200 flow analyzer system was used to evaluate ICAM-1, VCAM-1, E-selectin, IL-6 and TNF-alpha in serum from PCOS subjects (Millipore, Austin, TX, USA).…”

Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation

“…miR-31 also seems to be associated with inflammation and increased interaction between leukocytes and endothelial cells, both common pathological features of diabetic vascular complications [6,30]. Further research is needed to reveal the specific role of this miRNA in the context of T2D in general and specifically in DN, and to confirm its potential as a biological marker of DN.…”

“…Similarly, leukocytes migrate to the vascular walls in inflammatory situations, a multistep process regulated by cytokines released by leukocytes and adhesion molecules in endothelial cells [27]. We have previously demonstrated that the different steps involved in leukocyte recruitment -namely leukocyte rolling and adhesion -are enhanced in T2D patients and even more pronounced in patients with DN [6]. In the present study, we confirm these observations and also demonstrate a positive correlation between miR-31 and PMN rolling velocity as Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry well as a negative correlation between miR-31 and PMN adhesion, suggesting that the regulation of leukocyte-endothelial cell interactions is associated with the regulation of this miRNA.…”

“…Adhesion molecules including intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1) or E-selectin are also implicated in the physiopathology of DN, favouring immune cell infiltration in renal tissues [5]. In this sense, we have previously shown that T2D patients with DN are characterized by oxidative stress, increased inflammation and adhesion molecule levels, together with enhanced interactions between leukocytes and endothelial cells [6].…”