Lymphocytes influence intracranial aneurysm formation and rupture: role of extracellular matrix remodeling and phenotypic modulation of vascular smooth muscle cells. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Sawyer, David; Pace, Lauren; Pascale, Crissey; Kutchin, Alexander; O'Neill, Brannan; Starke, Robert; Dumont, Aaron
• Is Part Of: Journal of neuroinflammation. Volume 13:Issue 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-12
• Subjects: Leukocyte -- Interleukin-6 -- Inflammation -- Cerebral aneurysm -- Subarachnoid hemorrhage -- Matrix metalloproteinase 2 -- Matrix metalloproteinase 9 -- Myosin heavy chain -- Rag1 mice; Central nervous system -- Diseases -- Periodicals; Inflammation -- Periodicals; 616.8
• DOI: 10.1186/s12974-016-0654-z
• Languages: English
• ISSNs: 1742-2094

Abstract

Abstract Background Intracranial aneurysms (IA) are increasingly recognized as a disease driven by chronic inflammation. Recent research has identified key mediators and processes underlying IA pathogenesis, but mechanistic understanding remains incomplete. Lymphocytic infiltrates have been demonstrated in patient IA tissue specimens and have also been shown to play an important role in abdominal aortic aneurysms (AAA) and related diseases such as atherosclerosis. However, no study has systematically examined the contribution of lymphocytes in a model of IA. Methods Lymphocyte-deficient (Rag1) and wild-type (WT; C57BL/6 strain) mice were subjected to a robust IA induction protocol. Rates of IA formation and rupture were measured, and cerebral artery tissue was collected and utilized for histology and gene expression analysis. Results At 2 weeks, the Rag1 group had significantly fewer IA formations and ruptures than the WT group. Histological analysis of unruptured IA tissue showed robust B and T lymphocyte infiltration in the WT group, while there were no differences in macrophage infiltration, IA diameter, and wall thickness. Significant differences in interleukin-6 (IL-6), matrix metalloproteinases 2 (MMP2) and 9 (MMP9), and smooth muscle myosin heavy chain (MHC) were observed between the groups. Conclusions Lymphocytes are key contributors to IA pathogenesis and provide a novel target for the prevention of IA progression and rupture in patients.