Arthritis Care & Research Vol. 69, No. 6, June 2017, pp 892–902 DOI 10.1002/acr.23011 V C 2016, American College of Rheumatology ORIGINAL ARTICLE Exercise in Takayasu Arteritis: Effects on Inflammatory and Angiogenic Factors and Disease-Related Symptoms DIEGO S. OLIVEIRA, SAMUEL K. SHINJO, MARILDA G. SILVA, ANA L. DE S  A-PINTO, FERNANDA R. LIMA, HAMILTON ROSCHEL, SUZANA B. V. MELLO, VAL  ERIA COSTA-HONG, MARIA C. C. IRIGOYEN, ROSA M. PEREIRA, AND BRUNO GUALANO Objective. To investigate the effects of acute and chronic exercise in female patients with remissive Takayasu arteritis (TAK). Methods. This was a 2-part prospective study. In study 1, cytokines and soluble tumor necrosis factor (TNF) receptors were assessed at rest and every 60 minutes during a 3-hour recovery period following an acute exercise session in TAK (n 5 11) and heathy control (n 5 10) groups. In study 2, a subsample from the TAK group (n 5 6) underwent a 12-week exercise training program. Before and after training, the acute session of aerobic exercise was performed and cytokines and soluble TNF recep- tors were assessed at the same time points described above. Muscle function, strength, aerobic capacity, endothelial function, quality of life, and walking impairment scores were evaluated. Results. In study 1, the acute session of aerobic exercise led to overall similar responses on cytokine kinetics in the TAK and heathy control groups. In study 2, the exercise training program did not exacerbate inflammatory cytokines in TAK patients, while the proinflammatory cytokine TNF was diminished both at rest and following the acute session of aerobic exercise. In addition, the exercise training program increased the pro-angiogenic factors vascular endothelial growth factor (at rest) and platelet-derived growth factor AA (at rest and in response to the acute session of aerobic exercise). The exercise training pro- gram improved muscle strength and function, whereas aerobic capacity, quality of life, and endothelial function parameters remained unchanged. Conclusion. Exercise could be a well-tolerated, safe, and effective intervention able to induce immunomodulatory and pro- angiogenic effects and to increase strength and function in patients with TAK. INTRODUCTION Takayasu arteritis (TAK) is a rare primary systemic vasculitis that affects primarily large caliber vessels such as the aorta and its main branches (1,2). This disease predominantly affects young female individuals (1). TAK is characterized by an inflammatory and infiltrative process in media and the adven- titia layer of blood vessels, which progresses to the intima layer. This process can lead to stenosis, occlusions, ectasia, and/or aneurysm of vessels (1–3). Consequently, TAK patients may experience a pulse reduction in 1 or more arteries, a blood pressure difference between arms, bruits of subclavian arteries and/or aorta, a vascular claudication in extremities and/or abdominal viscera, and a peripheral ischemia (1,2). TAK patients often show a cluster of cardiovascular and metabolic abnormalities, including increased cholesterol and triglycerides levels, and decreased high-density lipoprotein cholesterol levels (4,5), a higher incidence of hypertension, an impaired insulin sensitivity and endothelial function, and an exacerbated inflammation. Furthermore, patients with periph- eral arterial disease, a condition that shares some similar vas- cular symptoms with TAK (e.g., claudication, peripheral ischemia), may experience decreased aerobic capacity, mus- cular strength, and muscular function (6,7). Altogether, these symptoms may confer an increased risk for cardiovascular events (5,8,9) and a poor quality of life with TAK (10–12). In this scenario, exercise emerges as a promising therapeutic tool to partially offset these adverse outcomes, similar to many other rheumatic diseases (13–16). However, there is a concern Clinicaltrials.gov identifier: NCT01501019. Supported by the Fundac ¸~ ao de Amparo  a Pesquisa do Estado de S~ ao Paulo, the Conselho Nacional de Des- envolvimento Cient  ıfico e Tecnol ogico, and the Coordenac¸~ ao de Aperfeic¸oamento de Pessoal de N  ıvel Superior. Diego S. Oliveira, MSc, Samuel K. Shinjo, MD, PhD, Marilda G. Silva, MSc, Ana L. de S a-Pinto, MD, PhD, Fernanda R. Lima, MD, PhD, Hamilton Roschel, PhD, Suzana B. V. Mello, MD, PhD, Val eria Costa-Hong, PhD, Maria C. C. Irigoyen, PhD, Rosa M. Pereira, MD, PhD, Bruno Gualano, PhD: School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. Address correspondence to Bruno Gualano, PhD, Disciplina de Reumatologia, Faculdade de Medicina da Universidade de S~ ao Paulo, S~ ao Paulo, Avenida Dr. Arnaldo, 455 3rd floor, Room 3190, S~ ao Paulo/SP, Brazil 01246-903. E-mail: gualano@ usp.br. Submitted for publication May 9, 2016; accepted in revised form August 9, 2016. 892