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| Author(s): |
Isabela Bruna Pires Borges
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2023-11-06 |
| Examining board members: |
Samuel Katsuyuki Shinjo;
Maria Elizabeth Rossi da Silva;
Fernando Henrique Carlos de Souza
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| Advisor: | Samuel Katsuyuki Shinjo |
| Abstract | |
Introduction: Recent studies have shown that statins are safe from clinical and laboratory points of view in patients with dyslipidemia and systemic autoimmune myopathies (e.g., such as dermatomyositis - DM, and antisynthetase syndrome - ASS). However, we do not know the possible impact of statins on the muscle tissues of these patients, and the gene expression of mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways in these muscle tissues, which motivated us to conduct the present study. Methods: This is the complement of a prospective, randomized, double-blind, placebo-controlled study, in which muscle tissue samples from patients with dyslipidemia and patients with DM or ASS were analyzed: six patients with DM and five with ASS received atorvastatin (20 mg/day) and two patients with DM and three with ASS received placebo (control group) for a period of 12 weeks. Transcriptome analysis (RNA-seq) was performed on vastus lateralis muscle samples obtained at baseline and after 12 weeks of drug intervention in all patients. The results were analyzed considering an expression change (over- or under-expressed) after treatment (atorvastatin or placebo) compared with pre-intervention control between 0.4 and -0.4 (on the log2 scale) and with a P value < 0.05. In the histological and histochemical analyses, cross-sections of frozen muscle tissues were performed, and specific stains were used to evaluate the morphological and functional characteristics of muscle fibers, presence of inflammatory infiltrates, interstitial fibrosis, and lipid content. The major histocompatibility complex (MHC) I analysis was performed using immunohistochemistry. Results: The mean age of the patients was 46.1 and 47.5 years, respectively, with the majority being female. All patients were stable according to International Myositis Assessment and Clinical Studies Group (IMACS) scores. In both groups (atorvastatin and placebo), there were no significant changes in genes related to the mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways. From a histological point of view, there was a slight variability in the fiber size that was preserved after the intervention. In addition, the mosaic of muscle fibers of types I and II was preserved in the internal architecture of the fibers and endomysial, perimysial, and perivascular regions. No fiber necrosis or atrophy, focal failures, subsarcolemmal accumulation, lipids, areas of fibrosis, or alterations in mitochondrial activity were observed. All muscle fibers were labeled for MHC I. Conclusions: Atorvastatin did not promote changes in the expression of genes related to mitochondrial, oxidative, insulin, lipid, and fibrogenesis pathways in muscle tissues of patients with DM and ASS. In addition, atorvastatin did not promote histological and histochemical changes in muscle tissues (AU) | |
| FAPESP's process: | 19/11367-9 - Molecular and metabolic analysis of Atorvastatin in the muscle tissues of patients with Systemic Autoimmune Myopathies |
| Grantee: | Isabela Bruna Pires Borges |
| Support Opportunities: | Scholarships in Brazil - Doctorate |