Evaluation of the serum levels of microparticles and of the efficacy of acetylsalicylic acid on vascular dysfunction markers in patients with systemic sclerosis

• Grant number: 18/15216-2
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2019
• End date: June 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Cristiane Kayser
• Grantee: Cristiane Kayser
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Carolina Nunes França ; Maria Cristina de Oliveira Izar

Abstract

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease, characterized by vascular damage, immune dysregulation and tissue fibrosis, with high morbidity, important functional disability and loss of quality of life, and elevated mortality. Microvascular abnormalities are present in the earliest stages of the disease, expressed mainly by Raynaud's phenomenon, which may precede cutaneous and visceral involvement for years. Platelet activation and, more recently, the role of microparticles, which are small membrane-bound vesicles released from activated or dying cells, have been involved in the pathogenesis of SSc Although several classes of drugs are used in the treatment of the vasculopathy of SSc, there is no therapeutic option to date that reverses vascular injury. Acetylsalicylic acid (ASA) is a drug with anti-inflammatory and antiplatelet action that may have a beneficial effect on the vascular manifestations of SSc.Objectives: In this study we aim at evaluating the microparticles levels and the efficacy of ASA on serum markers of platelet activation and endothelial damage and on the microvascular blood flow by means of laser Doppler imaging (LDI) measurement in patients with SSc. Methods: This will be a randomized double-blind, placebo-controlled trial, with 70 patients with SSc, randomly assigned in two groups of 35 patients; one group will receive ASA 100 mg per day, and the other group will receive placebo once daily (identical tablets) for 04 weeks. Patients will be evaluated at baseline and 4 weeks after the treatment by measuring the levels of microparticles derived from platelets (CD42+/CD31+), endothelial cells (CD51+CD105+), and monocytes (CD14+) using flow cytometry, and of von Willebrand factor (VWF), and thromboxane B2 using ELISA. The microvascular blood flow will also be measured using laser Doppler imaging before and after cold stimulus at baseline and at 4 weeks. Clinical and capillaroscopy data will be collected from all patients at baseline. A control group with 35 healthy subjects will also be included for the comparison of the serum levels of microparticles between them and patients with SSc. Correlations between serum markers and clinical and capillaroscopic abnormalities will be performed. Expected results: We expect to find a reduction in serum levels of platelet activation and endothelial damage markers in SSc patients treated with ASA compared to the placebo group, thus showing a possible benefit of this antiplatelet agent on SSc vasculopathy. We also intend to find a significant difference in the serum levels of microparticles of SSc patients in relation to healthy controls. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANDRA MAXIMIANO DE OLIVEIRA; IGHOR LUIZ DE AZEVEDO TEIXEIRA; CAROLINA NUNES FRANÇA; MARIA CRISTINA DE OLIVEIRA IZAR; CRISTIANE KAYSER. Microparticles: potential new contributors to the pathogenesis of systemic sclerosis?. ADVANCES IN RHEUMATOLOGY, v. 63, 2023-09-01. (18/15216-2)

DE OLIVEIRA, S. MAXIMIANO; TEIXEIRA, I. L. DE AZEVEDO; FRANCA, C. NUNES; IZAR, M. C. DE OLIVEIRA; KAYSER, C.. PLATELET-DERIVED MICROPARTICLES IN SYSTEMIC SCLEROSIS: POTENTIAL NEW PROFIBROTIC BIOMARKER?. ANNALS OF THE RHEUMATIC DISEASES, v. 81, p. 2-pg., 2022-06-01. (18/15216-2)