Vascular endothelial growth factor is highly expressed in muscle tissue of patients with polymyositis and patients with dermatomyositis

Abstract

Objective. To investigate the expression of vascular endothelial growth factor (VEGF) in muscle biopsy specimens and serum from patients with polymyositis and patients with dermatomyositis compared with that in healthy control subjects.Methods. Muscle biopsy specimens from 33 patients with polymyositis or dermatomyositis and 15 healthy control subjects and serum samples from 56 patients and 56 healthy control subjects were analyzed. Patients were categorized into 3 groups, depending on disease duration and the presence or absence of inflammatory infiltrates. The expression of VEGF and the vessel marker CD31 in muscle was analyzed by immunohistochemistry, the expression of VEGF messenger RNA (mRNA) was analyzed by in situ hybridization, and serum levels of VEGF were determined by enzymelinked immunosorbent assay.Results. Patients with polymyositis or dermatomyositis in the early or chronic phase without inflammatory infiltrates had a decreased total number of capillaries compared with healthy individuals. In patients with early disease without inflammatory infil-

Dysfunction of endothelial progenitor cells is associated with the type I IFN pathway in patients with polymyositis and dermatomyositis

“…Some of the organ manifestations, such as skin rash and low muscle endurance, could possibly be explained by a loss of microvessels. A low number of capillaries in muscle biopsies is a hallmark of DM, and was reported as an early finding also in PM [2]. Thus loss of microvessels may contribute to the pathogenesis of PM/DM and promote organ ischaemia and myofibre atrophy.…”

Perfil de citocinas angiogênicas séricas em pacientes com dermatomiosite

“…Atua na fisiopatogênese de doenças reumatológicas, como lúpus eritematoso sistêmico, artrite reumatoide, osteoartrite e osteoporose (Kikuchi et al, 1998;Yuan et al, 2014) e níveis aumentados já foram encontrados na esclerose sistêmica, DM e polimiosite (PM) (Grundtman et al, 2008;Kikuchi et al, 1998;Volpi et al, 2013).…”

“…Por ser importante citocina relacionada à angiogênese e inflamação, níveis séricos aumentados de VEGF vêm sendo documentados em várias doenças autoimunes, como esclerose sistêmica, lúpus eritematoso sistêmico, artrite reumatoide, artrite psoriásica, doença de Behçet, DM e polimiosite (Grundtman et al, 2008;Kikuchi et al, 1998;Yuan et al, 2014;Wei et al, 2015).…”

“…A fibra muscular é uma potencial fonte de VEGF como observado pela detecção de mRNA e expressão proteica tanto em pacientes saudáveis (Brutsaert et al, 2002;Gustafsson et al, 2002) quanto com DM (Grundtman et al, 2008;Volpi et al, 2013).…”

“…Já foi verificado que em fases inicias ou tardias crônicas e tratadas da DM pode-se encontrar uma redução do número de capilares no tecido muscular. Em pacientes com diagnóstico precoce e sem infiltrado inflamatório celular abundante em biópsias, foram encontradas muitas fibras musculares expressando VEGF comparadas com indivíduos saudáveis (Grundtman et al, 2008). Acredita-se, portanto, que os níveis elevados de VEGF no músculo nesses casos estejam relacionados com a hipóxia do tecido muscular ocasionada pela diminuição da eficiência capilar e modificações fenotípicas das células endoteliais, ocasionando mudanças metabólicas que contribuiriam para a fadiga muscular nesses pacientes (Grundtman et al, 2008;Olsen e Park, 1995, 1997.…”