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Updated: May 1, 2026
Induction and Micro-CT Imaging of Cerebral Cavernous Malformations in Mouse Model
Published on: September 4, 2017
Systems biology and proteomic analysis of cerebral cavernous malformation
Alexander R Edelmann1, Sarah Schwartz-Baxter, Christopher F Dibble
1Department of Prosthodontics and the Dental Research Center, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599, USA.
Unlabelled:
Cerebral cavernous malformations (CCM) are vascular anomalies caused by mutations in genes encoding KRIT1, OSM and PDCD10 proteins causing hemorrhagic stroke. We examine proteomic change of loss of CCM gene expression. Using human umbilical vein endothelial cells, label-free differential protein expression analysis with multidimensional liquid chromatography/tandem mass spectrometry was applied to three CCM protein knockdown cell lines and two control cell lines: ProteomeXchange identifier PXD000362. Principle component and cluster analyses were used to examine the differentially expressed proteins associated with CCM. The results from the five cell lines revealed 290 and 192 differentially expressed proteins (p < 0.005 and p < 0.001, respectively). Most commonly affected proteins were cytoskeleton-associated proteins, in particular myosin-9. Canonical genetic pathway analysis suggests that CCM may be a result of defective cell-cell interaction through dysregulation of cytoskeletal associated proteins.
Conclusion:
The work explores signaling pathways that may elucidate early detection and novel therapy for CCM.
Insights
Cerebral cavernous malformations (CCM) involve gene mutations leading to hemorrhagic stroke. Loss of CCM gene expression alters proteins, particularly cytoskeleton-associated ones like myosin-9, impacting cell interactions.
Area of Science:
- Biochemistry
- Molecular Biology
- Vascular Biology
Background:
- Cerebral cavernous malformations (CCM) are vascular anomalies linked to mutations in KRIT1, OSM, and PDCD10.
- These mutations can lead to debilitating hemorrhagic strokes.
Purpose of the Study:
- To investigate proteomic changes resulting from the loss of CCM gene expression.
- To identify key proteins and pathways affected in CCM.
Main Methods:
- Utilized human umbilical vein endothelial cells with knockdown of CCM genes.
- Performed label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (ProteomeXchange ID: PXD000362).
- Applied principle component and cluster analyses to identify differentially expressed proteins.
Main Results:
- Identified 290 and 192 differentially expressed proteins (p < 0.005 and p < 0.001, respectively).
- Found that cytoskeleton-associated proteins, notably myosin-9, were most commonly affected.
- Pathway analysis indicated dysregulation of cytoskeletal proteins may cause defective cell-cell interactions in CCM.
Conclusions:
- CCM pathogenesis may involve impaired cell-cell interactions due to altered cytoskeletal protein regulation.
- This research provides insights into signaling pathways relevant for early CCM detection and novel therapeutic strategies.
