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Subcutaneous Angiotensin II Infusion using Osmotic Pumps Induces Aortic Aneurysms in Mice
Published on: September 28, 2015
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Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm
Munish Kumar1, Krishna Patel2, Shobia Chinnapparaj1
1Division of Neuro-anesthesia, Department of Anesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Translational Stroke Research
|August 29, 2023
Summary
Researchers identified key molecules and pathways involved in intracranial aneurysm (IA) formation and rupture. Understanding these molecular changes, like SPARC, OSM, and CTSL, could lead to better diagnostic strategies for IA.
Area of Science:
- Molecular biology
- Genomics
- Pathology
Background:
- Intracranial aneurysms (IA) pose a rupture risk, necessitating improved diagnostic and screening methods.
- Current understanding of IA molecular pathology is insufficient for effective risk stratification.
- Identifying molecular drivers is crucial for developing novel diagnostic strategies.
Purpose of the Study:
- To identify dysregulated genes (DGs) in intracranial aneurysms (IA) using transcriptomics.
- To elucidate the molecular basis of IA formation and rupture.
- To validate candidate genes and signaling pathways involved in IA pathogenesis.
Main Methods:
- RNA-sequencing (RNA-Seq) on tissue samples from controls, unruptured IA, and ruptured IA.
- Identification and functional analysis of dysregulated genes (DGs).
- Validation of candidate genes at transcript and protein levels.
Main Results:
- 314 DGs identified in unruptured IA vs. controls; SPARC and OSM validated as key molecules.
- PI3K-AKT signaling pathway implicated in IA formation.
- 301 DGs identified in ruptured IA vs. unruptured IA; CTSL validated as a key molecule.
- Hippo signaling pathway and YAP1 gene regulation linked to IA rupture.
Conclusions:
- Activation of PI3K-AKT signaling by OSM and SPARC upregulation contribute to IA formation.
- PI3K-AKT signaling regulates the Hippo pathway, downregulating YAP1.
- CTSL upregulation, coupled with YAP1 downregulation, weakens the aneurysm wall, promoting rupture.
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