Abstract
Objectives
Recent experimental studies have defined intracranial aneurysms as a macrophage-mediated
chronic inflammatory disease affecting intracranial arteries. Although there are various
subtypes in macrophages, what type of macrophages is present in lesions during the
disease development remains to be elucidated.
Methods
The previously-established aneurysm model of rats was used. Macrophages were labeled
with the fluorescent protein and isolated by a laser-microdissection method. The comprehensive
gene expression profile analyses and gene ontology analyses was then done to identify
a macrophage subtype present in lesions at the growth phase.
Results
The gene expression profile data of total 52 macrophages infiltrating into the lesions
was acquired. The principal component analysis revealed the monotonous macrophage
subtype. By comparing the profile identified with one from in vitro-differentiated
M0 or M1 macrophages, the macrophages in the lesions were belonged to the simple and
unique subtype. Because the perception of signaling from nervous system was highlighted
as up-represented terms through gene ontology analyses, the macrophage subtype in
lesions at the growth phase might be differentiated under the influence of nervous
system in the microenvironment. The histopathological examinations supported the above
notion by confirming the presence of nerves in the adventitia.
Conclusions
The findings from the present study have provided the useful insights about the macrophage
subtype in aneurysm lesions at the growth phase and also proposed its ability as a
therapeutic target.
Key Words
Abbreviations:
CCA (common carotid artery), GO (gene ontology), IA (intracranial aneurysm), SAH (subarachnoid hemorrhage)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Stroke and Cerebrovascular DiseasesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Subarachnoid Hemorrhage.N Engl J Med. 2017; 377: 257-266
- Aneurysmal Subarachnoid Hemorrhage: the Last Decade.Transl Stroke Res. 2021; 12: 428-446
- The natural course of unruptured cerebral aneurysms in a Japanese cohort.N Engl J Med. 2012; 366: 2474-2482
- Unruptured aneurysms.J Neurosurg. 2002; 96 (discussion 58-60): 50-51
- Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis.Stroke. 2007; 38: 1404-1410
- Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies, The Lancet.Neurology. 2014; 13: 59-66
- Prostaglandin E2-EP2-NF-kappaB signaling in macrophages as a potential therapeutic target for intracranial aneurysms.Sci Signal. 2017; 10: eaah6037
- Impact of monocyte chemoattractant protein-1 deficiency on cerebral aneurysm formation.Stroke. 2009; 40: 942-951
- Macrophage-derived matrix metalloproteinase-2 and -9 promote the progression of cerebral aneurysms in rats.Stroke. 2007; 38: 162-169
- NF-kappaB is a key mediator of cerebral aneurysm formation.Circulation. 2007; 116: 2830-2840
- PGE(2) -EP(2) signalling in endothelium is activated by haemodynamic stress and induces cerebral aneurysm through an amplifying loop via NF-kappaB.Br J Pharmacol. 2011; 163: 1237-1249
- Critical roles of macrophages in the formation of intracranial aneurysm.Stroke. 2011; 42: 173-178
- Two Diverse Hemodynamic Forces, a Mechanical Stretch and a High Wall Shear Stress, Determine Intracranial Aneurysm Formation.Transl Stroke Res. 2020; 11: 80-92
- Involvement of neutrophils in machineries underlying the rupture of intracranial aneurysms in rats.Sci Rep. 2020; 10: 20004
- Critical role of TNF-alpha in cerebral aneurysm formation and progression to rupture.J Neuroinflammation. 2014; 11: 77
- Intracranial Aneurysm as a Macrophage-mediated Inflammatory Disease.Neurol Med Chir (Tokyo). 2019; 59: 126-132
- Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms.Neurosurg Focus. 2019; 47: E21
- Inflammatory changes in the aneurysm wall: a review.J Neurointerv Surg. 2018; 10: i58-i67
- Vascular Macrophages as Therapeutic Targets to Treat Intracranial Aneurysms.Front Immunol. 2021; 12630381
- Pitavastatin suppresses formation and progression of cerebral aneurysms through inhibition of the nuclear factor kappaB pathway.Neurosurgery. 2009; 64 (discussion 365-366): 357-365
- Simvastatin suppresses the progression of experimentally induced cerebral aneurysms in rats.Stroke. 2008; 39: 1276-1285
- A sphingosine-1-phosphate receptor type 1 agonist, ASP4058, suppresses intracranial aneurysm through promoting endothelial integrity and blocking macrophage transmigration.Br J Pharmacol. 2017; 174: 2085-2101
- Macrophage subsets in atherosclerosis.Nat Rev Cardiol. 2015; 12: 10-17
- Diversity of macrophage phenotypes and responses in atherosclerosis.Cell Mol Life Sci. 2020; 77: 1919-1932
- Macrophage plasticity and polarization in tissue repair and remodelling.J Pathol. 2013; 229: 176-185
- Exploring the full spectrum of macrophage activation.Nat Rev Immunol. 2008; 8: 958-969
- Macrophage Polarization in Atherosclerosis. 2022; 13 (Genes (Basel))
- Implications of macrophage polarization in autoimmunity.Immunology. 2018; 154: 186-195
- Macrophages in wound healing: activation and plasticity.Immunol Cell Biol. 2019; 97: 258-267
- Macrophage plasticity, polarization, and function in health and disease.J Cell Physiol. 2018; 233: 6425-6440
- Diverse roles of macrophage polarization in aortic aneurysm: destruction and repair.J Transl Med. 2018; 16: 354
- Macrophage imbalance (M1 vs. M2) and upregulation of mast cells in wall of ruptured human cerebral aneurysms: preliminary results.J Neuroinflammation. 2012; 9: 222
- Hemodynamic Force as a Potential Regulator of Inflammation-Mediated Focal Growth of Saccular Aneurysms in a Rat Model.J Neuropathol Exp Neurol. 2021; 80: 79-88
- Induction of CCN1 in growing saccular aneurysms: a potential marker predicting unstable lesions.J Neuropathol Exp Neurol. 2021; 80: 695-704
- Macrophage-derived inflammation induces a transcriptome makeover in mesenchymal stromal cells enhancing their potential for tissue repair.Int J Mol Sci. 2021; 22
- Risk factors for fatal subarachnoid hemorrhage: the Japan Collaborative Cohort Study.Stroke. 2003; 34: 2781-2787
- Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease.Circulation. 2020; 142: 455-465
- Macrophage imaging of cerebral aneurysms with ferumoxytol: an exploratory study in an animal model and in patients.J Stroke Cerebrovasc Dis. 2016;
- Macrophage imaging within human cerebral aneurysms wall using ferumoxytol-enhanced MRI: a pilot study.Arterioscler Thromb Vasc Biol. 2012; 32: 1032-1038
- Macrophage Imaging of Intracranial Aneurysms.Neurol Med Chir (Tokyo). 2019; 59: 257-263
Article info
Publication history
Published online: October 29, 2022
Accepted:
October 18,
2022
Received in revised form:
October 5,
2022
Received:
August 17,
2022
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106848
Copyright
© 2022 Elsevier Inc. All rights reserved.