TY - JOUR
T1 - Case Report
T2 - Exercise-associated changes of leukocyte gene expression in statin-associated myopathy
AU - Bondar, Galyna
AU - Mahapatra, Abhinandan Das
AU - Silacheva, Irina
AU - Bao, Tra Mi
AU - Vu, Thomas
AU - Su, Stephanie
AU - Hairapetian, Adrian
AU - Katappagari, Ananya
AU - Galan, Liana
AU - Chandran, Joshua
AU - Adamov, Ruben
AU - Yang, Alan
AU - Bukkapatnam, Ananya
AU - Mansouri, Pejman
AU - Mirchandani, Mahi
AU - Dang, Nathan
AU - Mancusi, Lorenzo
AU - Lai, Isabel
AU - Rahman, Anca
AU - Grogan, Tristan
AU - Hsu, Jeffrey
AU - Cappelletti, Monica
AU - Ping, Pei Pei
AU - Elashoff, David
AU - Reed, Elaine F.
AU - Deng, Mario C.
N1 - Publisher Copyright:
Copyright © 2025 Bondar, Mahapatra, Silacheva, Bao, Vu, Su, Hairapetian, Katappagari, Galan, Chandran, Adamov, Yang, Bukkapatnam, Mansouri, Mirchandani, Dang, Mancusi, Lai, Rahman, Grogan, Hsu, Cappelletti, Ping, Elashoff, Reed and Deng.
PY - 2025
Y1 - 2025
N2 - Background: Statin-associated muscle symptoms (SAMS) are a significant clinical issue, and their exact cause is not well understood. Immunological mechanisms have been suggested but have not been confirmed. This study is a rare, longitudinal case-based analysis that uses transcriptomics to explore immune-related gene expression changes in peripheral blood mononuclear cells (PBMCs) in response to exercise before, during, and after the onset and resolution of SAMS. Methods: A healthy volunteer (HV1) enrolled in an exercise immuno-fitness study underwent cardiopulmonary exercise testing (CPX) with blood collected at three timepoints: pre-exercise (TP1), peak exercise (TP2), and 1 hour post-exercise (TP3). After baseline testing (Visit 1), the participant began statin therapy on their own, developed SAMS, and had repeat CPX testing during the symptomatic phase (Visit 2) and partial recovery phase (Visit 3). RNA was extracted from PBMCs and analyzed using next-generation RNA sequencing. The data were evaluated using differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Pathway and gene ontology enrichment were used to identify immunologic signatures associated with SAMS. Results: The PBMC gene expression profiles showed distinct changes during SAMS compared to the baseline and recovery phases. WGCNA identified 39 co-expression modules. Several modules had high expression at peak exercise in the healthy state (V1), which was attenuated in SAMS (V2) and partially restored in recovery (V3). Gene ontology and Reactome analyses of key modules identified 16 genes that were differentially expressed at peak exercise and may be involved in specific immune pathways in SAMS pathogenesis. Conclusion: This case study suggests that profiling the exercise-induced immune transcriptome can reveal dynamic immunological changes related to statin-induced myopathy. These findings support the hypothesis of an immune-mediated component in SAMS and provide a basis for future studies to validate transcriptomic biomarkers for the early detection and management of SAMS.
AB - Background: Statin-associated muscle symptoms (SAMS) are a significant clinical issue, and their exact cause is not well understood. Immunological mechanisms have been suggested but have not been confirmed. This study is a rare, longitudinal case-based analysis that uses transcriptomics to explore immune-related gene expression changes in peripheral blood mononuclear cells (PBMCs) in response to exercise before, during, and after the onset and resolution of SAMS. Methods: A healthy volunteer (HV1) enrolled in an exercise immuno-fitness study underwent cardiopulmonary exercise testing (CPX) with blood collected at three timepoints: pre-exercise (TP1), peak exercise (TP2), and 1 hour post-exercise (TP3). After baseline testing (Visit 1), the participant began statin therapy on their own, developed SAMS, and had repeat CPX testing during the symptomatic phase (Visit 2) and partial recovery phase (Visit 3). RNA was extracted from PBMCs and analyzed using next-generation RNA sequencing. The data were evaluated using differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Pathway and gene ontology enrichment were used to identify immunologic signatures associated with SAMS. Results: The PBMC gene expression profiles showed distinct changes during SAMS compared to the baseline and recovery phases. WGCNA identified 39 co-expression modules. Several modules had high expression at peak exercise in the healthy state (V1), which was attenuated in SAMS (V2) and partially restored in recovery (V3). Gene ontology and Reactome analyses of key modules identified 16 genes that were differentially expressed at peak exercise and may be involved in specific immune pathways in SAMS pathogenesis. Conclusion: This case study suggests that profiling the exercise-induced immune transcriptome can reveal dynamic immunological changes related to statin-induced myopathy. These findings support the hypothesis of an immune-mediated component in SAMS and provide a basis for future studies to validate transcriptomic biomarkers for the early detection and management of SAMS.
KW - exercise-associated changes
KW - immunological fitness
KW - peripheral blood mononuclear cell transcriptome profiling
KW - statin-associated adverse effects
KW - statin-associated myopathy
KW - statin-myopathy
UR - https://www.scopus.com/pages/publications/105025523550
UR - https://www.scopus.com/pages/publications/105025523550#tab=citedBy
U2 - 10.3389/fphar.2025.1695543
DO - 10.3389/fphar.2025.1695543
M3 - Article
AN - SCOPUS:105025523550
SN - 1663-9812
VL - 16
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 1695543
ER -