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

• Grant number: 19/11367-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2019
• End date: October 12, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Samuel Katsuyuki Shinjo
• Grantee: Isabela Bruna Pires Borges
• Host 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

(9)

(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. (18/08735-3, 19/12155-5, 19/11367-9, 19/11776-6)

OLIVO PALLO, PABLO ARTURO; HOFF, LEONARDO SANTOS; PIRES BORGES, ISABELA BRUNA; TORRES-RUIZ, JIRAM; CASSIANO-QUEZADA, FABIOLA; GRANEL, AMELIA; GOMEZ, GRACIELA; PISONI, CECILIA; GOMEZ, RAMIRO; SHINJO, SAMUEL KATSUYUKI. Characterization of Patients With Dermatomyositis According to Anti-Melanoma Differentiation-Associated Gene-5 Autoantibodies in Centers from 3 Latin American Countries A Cohort Study. JCR-JOURNAL OF CLINICAL RHEUMATOLOGY, v. 28, n. 2, p. 5-pg., 2022-03-01. (19/11776-6, 19/11367-9)

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. (19/11367-9, 18/08735-3, 19/12155-5, 19/11776-6)

CARBONI TRUZZI, NATASSIA CRISTINA; HOFF, LEONARDO SANTOS; PIRES BORGES, ISABELA BRUNA; CARLOS DE SOUZA, FERNANDO HENRIQUE; SHINJO, SAMUEL KATSUYUKI. Clinical manifestations, outcomes, and antibody profile of Brazilian adult patients with dermatomyositis: a single-center longitudinal study. ADVANCES IN RHEUMATOLOGY, v. 62, n. 1, p. 9-pg., 2022-11-12. (21/04892-0, 19/11776-6, 19/11367-9)

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. (16/19771-5, 19/11367-9, 17/13109-1)

DOS SANTOS, ALEXANDRE MOURA; MISSE, RAFAEL GIOVANI; PIRES BORGES, ISABELA BRUNA; GOMES DA SILVA, SARAH LUIZA; KIM, ANA WOO SOOK; PEREIRA, ROSA MARIA R.; SHINJO, SAMUEL KATSUYUKI. High prevalence of fatigue in patients with Takayasu arteritis: a case-control study in a Brazilian centre. RHEUMATOLOGY ADVANCES IN PRACTICE, v. 6, n. 2, p. 9-pg., 2022-05-06. (19/12155-5, 20/10691-4, 19/11776-6, 19/11367-9)

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. (18/08735-3, 19/11367-9, 19/12155-5)

CAETANO, ALINE MARQUES; BORGES, ISABELA BRUNA PIRES; DA SILVA, LILA MORENA BUENO; SHINJO, SAMUEL KATSUYUKI. High prevalence of necrotizing myofibers in adult dermatomyositis muscle biopsies. CLINICAL RHEUMATOLOGY, v. 41, n. 11, p. 7-pg., 2022-07-11. (19/11776-6, 19/11367-9)

DE OLIVEIRA, DIEGO SALES; BORGES, ISABELA BRUNA PIRES; MARIE, SUELY KAZUE NAGAHASHI; LERARIO, ANTONIO MARCONDES; OBA-SHINJO, SUELI MIEKO; SHINJO, SAMUEL KATSUYUKI. Exercise training attenuates skeletal muscle fat infiltration and improves insulin pathway of patients with immune-mediated necrotizing myopathies and dermatomyositis. ARCHIVES OF RHEUMATOLOGY, v. 38, n. 2, p. 11-pg., 2023-06-01. (19/11367-9, 16/19771-5, 17/13109-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BORGES, Isabela Bruna Pires. Impact of atorvastatin in muscle tissues of patients with dermatomyositis and antisynthetase syndrome. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.