The Onset of Systemic Oxidative Stress Associated with the Accumulation of Lipid Peroxidation Product Acrolein in the Skin of Patients with Small-Vessel Vasculitis.

Vesna Sredoja Tisma,Jadranka Morovic-Vergles,Josko Mitrovic,Kresimir Galesic,Morana Jaganjac,Koji Uchida,Neven Zarkovic,Stela Bulimbasic,Danica Galesic Ljubanovic,Franz Tatzber

doi:10.3390/molecules26082344

Abstract

Small-vessel vasculitis (SVV) is the inflammation of the vessel wall that can result in hemorrhage and/or ischemia. Among the histological findings in SVV are increased infiltrating neutrophils, which, due to their oxidative burst and myeloperoxidase activity, release excessive reactive oxygen species, triggering a chain reaction of lipid peroxidation and yielding reactive aldehydes such as acrolein. The implication of oxidative stress in the pathogenesis of SVV was studied, focusing on acrolein immunohistochemistry in the affected skin vessels and systemic stress response. Samples from SVV patients and healthy subjects were collected and analyzed for total serum peroxides, total antioxidant capacity, inflammatory and immunological parameters, as well as for the presence of acrolein–protein adducts in the skin tissue specimens. The obtained data showed that systemic redox homeostasis and iron metabolism are altered in SVV patients. Possible biomarkers in the evaluation of oxidative status, disease activity and prevalence were indicated. Furthermore, a strong correlation between the accumulation of acrolein–protein adducts in the skin and the progression of the disease was revealed. Thus, the results of this study demonstrate that SVV is not only associated with systemic oxidative stress but also with tissue-specific oxidative stress that promotes acrolein formation and protein modification correlating with the severity of cutaneous vasculitis.

Highlights

Vasculitis is the inflammation of blood vessels that can cause damage to vessel walls, leading to hemorrhage and/or ischemia [1,2]
We investigated the association of inflammation, inflammatory parameters, iron metabolism and systemic redox homeostasis with the pathology of Small-vessel vasculitis (SVV) and, for the first time, the involvement of acrolein in the pathology of SVV disease
It should be mentioned that aging of the skin itself, especially in the case of photoaging, is associated with chronic inflammatory processes, oxidative stress and lipid peroxidation

Summary

Introduction

Vasculitis is the inflammation of blood vessels that can cause damage to vessel walls, leading to hemorrhage and/or ischemia [1,2]. Small-vessel vasculitis (SVV) is a vasculitis that affects small intraparenchymal arteries, arterioles, capillaries, venules and veins [2]. According to the 2012 Revisited International Chapel Hill Consensus Conference Nomenclature of Vasculitides, cutaneous vasculitis is included in both SVV and single-organ vasculitis groups of nomenclature [2]. The skin, as the largest human organ with a large vascular bed, is often involved in many vasculitis syndromes [3]. Cutaneous vasculitis can be either a primary (idiopathic) disorder or a secondary disorder resulting from drug administration such as beta-lactam antibiotics, thiazide diuretics or nonsteroidal anti-inflammatory drugs. Food or food additives, infection or diseases such as connective tissue disease, inflammatory bowel disease, paraproteinemia and malignancies may trigger the development of cutaneous vasculitis [3,4]

Methods

Results

Conclusion