Molecular and metabolic analysis of Atorvastatin in the muscle tissues of patients with Systemic Autoimmune Myopathies

• Grant number: 19/11367-9
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2019
• Effective date (End): September 30, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Samuel Katsuyuki Shinjo
• Grantee: Isabela Bruna Pires Borges
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The present study is a complement to the Master's project, whose objective was to evaluate the safety of atorvastatin in patients with Systemic Autoimmune Myopathies (SAM). In a randomized, double-blind, placebo-controlled clinical trial, 14 patients with SAM received atorvastatin calcium (20 mg/day) and 6 patients with SAM received one tablet - placebo/day for a period of 12 weeks. The medication promoted a significant reduction of the serum LDL-cholesterol level in the atorvastatin group. Furthermore, it was safe, without adverse events and without promoting disease relapses. Despite these promising results at clinical level, we do not know the safety of the use of statins also at molecular and metabolic point of view in muscle tissues. Studies in individuals without SAM have shown that statins may eventually promote some muscle damage caused primarily by dysfunction of mitochondrial activity, increase the fibrogenic process and, at the metabolic level, increase insulin resistance in muscle tissues and lead to an increased risk of developing Diabetes Mellitus. Of note, all of our patients had undergone two tests, but they were not evaluated in the Master's project: Oral Glucose Tolerance Test (OGTT) and muscle biopsy - at baseline and after 12 weeks of follow-up. Thus, in the present study, we initially aim the analysis of muscular biopsies at molecular (genetic and protein) and metabolic (glycemic, lipid, oxidative and fibrogenesis) levels. Secondarily, the goal is to perform a histological and immune-histochemical analysis of the muscle tissues of patients with SAM who underwent atorvastatin or placebo. In addition, a profile analysis of cytokines related to inflammatory and lipidic processes will be performed, as well as an analysis of insulin resistance through the OGTT curve of patients submitted to atorvastatin or placebo. Elucidating this information will be important in clinical practice, allowing better therapeutic management of dyslipidemia found in patients with SAM. (AU)

Scientific publications

(5)

(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)

DOS SANTOS, ALEXANDRE MOURA; MISSE, RAFAEL GIOVANI; PIRES BORGES, ISABELA BRUNA; BUORO PERANDINI, LUIZ AUGUSTO; SHINJO, SAMUEL KATSUYUKI. Physical exercise for the management of systemic autoimmune myopathies: recent findings, and future perspectives. CURRENT OPINION IN RHEUMATOLOGY, v. 33, n. 6, p. 563-569, NOV 2021. Web of Science Citations: 0.

MISSE, RAFAEL GIOVANI; BORGES, ISABELA BRUNA PIRES; DOS DANTOS, ALEXANDRE MOURA; GUPTA, LATIKA; SHINJO, SAMUEL KATSUYUKI. Effect of exercise training on fatigue and pain in patients with systemic autoimmune myopathies: A systematic review. AUTOIMMUNITY REVIEWS, v. 20, n. 10 OCT 2021. Web of Science Citations: 1.

PIRES BORGES, ISABELA BRUNA; DE OLIVEIRA, DIEGO SALES; NAGAHASHI MARIE, SUELY KAZUE; LENARIO, ANTONIO MARCONDES; OBA-SHINJO, SUELI MIEKO; SHINJO, SAMUEL KATSUYUKI. Exercise Training Attenuates Ubiquitin-Proteasome Pathway and Increases the Genes Related to Autophagy on the Skeletal Muscle of Patients With Inflammatory Myopathies. JCR-JOURNAL OF CLINICAL RHEUMATOLOGY, v. 27, n. 6, p. S224-S231, SEP 2021. Web of Science Citations: 0.

DOS SANTOS, ALEXANDRE MOURA; MISSE, RAFAEL GIOVANI; BORGES, ISABELA BRUNA PIRES; GUALANO, BRUNO; DE SOUZA, ALEXANDRE WAGNER SILVA; TAKAYAMA, LILIAM; PEREIRA, ROSA MARIA R.; SHINJO, SAMUEL KATSUYUKI. Increased modifiable cardiovascular risk factors in patients with Takayasu arteritis: a multicenter cross-sectional study. ADVANCES IN RHEUMATOLOGY, v. 61, n. 1 JAN 8 2021. Web of Science Citations: 0.

ALEXANDRE MOURA DOS SANTOS; RAFAEL GIOVANI MISSE; ISABELA BRUNA PIRES BORGES; BRUNO GUALANO; ALEXANDRE WAGNER SILVA DE SOUZA; LILIAM TAKAYAMA; ROSA MARIA R. PEREIRA; SAMUEL KATSUYUKI SHINJO. Increased modifiable cardiovascular risk factors in patients with Takayasu arteritis: a multicenter cross-sectional study. ADVANCES IN RHEUMATOLOGY, v. 61, p. -, 2021.