Transcriptomic profiling of temporal muscle tissues revealed that a collagen-rich extracellular matrix signature and the balance between collagen deposition and remodelling may modulate surgical efficacy in moyamoya disease indirect revascularization.
Key Findings
Results
Pathways related to the extracellular matrix and collagen family were significantly enriched in patients with good postoperative collateralization compared to those with poor collateralization.
Patients were categorized into Good (Matsushima Grade A, n=13) and Poor (Matsushima Grade C, n=12) collateralization groups based on postoperative angiography.
Comprehensive transcriptome-wide RNA sequencing was performed on temporal muscle tissues harvested during surgery.
ECM and collagen family pathways were identified as significantly enriched in the Good group through differentially expressed gene (DEG) analysis.
Results suggest 'a pivotal role for collagens in promoting postoperative angiogenesis.'
Results
COL1A1, a core ECM component, was upregulated in the Good collateralization group as validated by quantitative real-time PCR.
qPCR validation was used to confirm transcriptomic findings.
COL1A1 upregulation in the Good group suggests active collagen deposition within the temporal muscle.
The finding indicates active ECM remodelling is associated with better postoperative angiogenesis outcomes.
Total study cohort consisted of 25 patients enrolled from a single centre using a prospective sampling, retrospective cohort design.
Results
MMP3, a matrix-degrading enzyme, was downregulated in the Good collateralization group as validated by quantitative real-time PCR.
MMP3 downregulation in the Good group was confirmed via qPCR.
Lower MMP3 expression alongside higher COL1A1 expression suggests a shift toward collagen deposition over degradation in better surgical outcomes.
The balance between COL1A1 (deposition) and MMP3 (degradation) is proposed to modulate surgical efficacy in MMD.
These findings indicate 'active ECM remodelling within the temporal muscle' is associated with good collateral formation.
Results
Paediatric patients exhibited a distinct transcriptional profile characterized by high collagen expression alongside altered expression of genes related to mitochondrial electron transport.
Subgroup analysis revealed distinct transcriptional profiles between paediatric and other patient subgroups.
Paediatric patients showed a cluster with both high collagen expression and altered mitochondrial electron transport gene expression.
This subgroup finding suggests age-related differences in the molecular mechanisms underlying postoperative angiogenesis in MMD.
The specific number of paediatric patients in this subgroup was not specified in the abstract.
Methods
The study employed a single-centre, prospective sampling, retrospective cohort design with temporal muscle tissue RNA sequencing to investigate angiogenesis mechanisms after indirect revascularization for moyamoya disease.
A total of 25 patients were enrolled (Good group n=13, Poor group n=12).
Temporal muscle tissues were harvested during surgery for comprehensive transcriptome-wide RNA sequencing.
Patient grouping was based on Matsushima grading from postoperative angiography (Grade A = Good, Grade C = Poor).
Key transcriptomic findings were validated via quantitative real-time PCR (qPCR).
What This Means
Moyamoya disease is a condition where the major arteries supplying blood to the brain become narrowed, requiring surgery to help grow new blood vessels. One common surgical approach involves placing the temporal muscle (a muscle near the temple) against the brain's surface so that new blood vessels can grow from the muscle into the brain. However, not all patients benefit equally from this surgery, and this study investigated why by analyzing the gene activity in temporal muscle tissue taken from patients during surgery. Researchers compared gene expression between patients who developed good new blood vessel networks after surgery versus those who did not.
This research suggests that patients who developed better new blood vessel networks after surgery had higher activity of genes related to collagen — the main structural protein that forms a scaffold in tissues — and the broader extracellular matrix (the molecular framework surrounding cells). Specifically, a gene called COL1A1, which helps build collagen, was more active in the good outcome group, while a gene called MMP3, which breaks down collagen, was less active. This combination points to an environment in the temporal muscle that favors building and maintaining a collagen-rich scaffold, which may support the growth of new blood vessels into the brain. In children specifically, this collagen activity pattern was also accompanied by changes in genes related to how cells generate energy.
These findings matter because they identify potential biological markers in the temporal muscle that may predict or influence surgical success in moyamoya disease. If a collagen-rich tissue environment is indeed important for blood vessel growth after this type of surgery, future research could explore whether interventions to support collagen production or reduce collagen breakdown might improve outcomes — particularly in patients who currently respond poorly to surgery. The study was relatively small (25 patients total), so larger studies are needed to confirm these findings.
Chen J, Xu S, Wang Z, Jin W, Liang R, Tu X. (2026). Transcriptomic Profiling Associates Collagen-Rich Extracellular Matrix With Postoperative Angiogenesis in Moyamoya Disease.. Journal of cellular and molecular medicine. https://doi.org/10.1111/jcmm.71267