Research Paper Volume 13, Issue 9 pp 12800—12816
Internal modulation of proteolysis in vascular extracellular matrix remodeling: role of ADAM metallopeptidase with thrombospondin type 1 motif 5 in the development of intracranial aneurysm rupture
- 1 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- 2 Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin, China
- 3 Department of Neuro-Oncology and Neurosurgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
Received: November 11, 2019 Accepted: February 16, 2021 Published: May 2, 2021https://doi.org/10.18632/aging.202948
How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Intracranial aneurysms (IAs) are common cerebrovascular diseases that carry a high mortality rate, and the mechanisms that contribute to IA formation and rupture have not been elucidated. ADAMTS-5 (ADAM Metallopeptidase with Thrombospondin Type 1 Motif 5) is a secreted proteinase involved in matrix degradation and ECM (extracellular matrix) remodeling processes, and we hypothesized that the dysregulation of ADAMTS-5 could play a role in the pathophysiology of IA. Immunofluorescence revealed that the ADAMTS-5 levels were decreased in human and murine IA samples. The administration of recombinant protein ADAMTS-5 significantly reduced the incidence of aneurysm rupture in the experimental model of IA. IA artery tissue was collected and utilized for histology, immunostaining, and specific gene expression analysis. Additionally, the IA arteries in ADAMTS-5-administered mice showed reduced elastic fiber destruction, proteoglycan accumulation, macrophage infiltration, inflammatory response, and apoptosis. To further verify the role of ADAMTS-5 in cerebral vessels, a specific ADAMTS-5 inhibitor was used on another model animal, zebrafish, and intracranial hemorrhage was observed in zebrafish embryos. In conclusion, our findings indicate that ADAMTS-5 is downregulated in human IA, and compensatory ADAMTS-5 administration inhibits IA development and rupture with potentially important implications for treating this cerebrovascular disease.