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Unique remodeling processes after vascular injury in intracranial arteries: analysis using a novel mouse model
Munehisa Shimamura1, Hironori Nakagami, Masataka Sata
1Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University Office for University-Industry Collaboration, Osaka, Japan.
Insights
Intracranial arteries show unique vascular remodeling after injury, including delayed neointimal growth and smooth muscle cell loss. These differences in intracranial atherosclerotic disease pathophysiology may explain poor outcomes from angioplasty and stenting.
Area of Science:
- Vascular Biology
- Translational Medicine
- Medical Device Research
Background:
- Intracranial atherosclerotic diseases pose challenges for angioplasty and stenting due to high restenosis and hemorrhage rates.
- The underlying pathophysiological mechanisms driving these adverse outcomes remain poorly understood.
Purpose of the Study:
- To investigate and compare the vascular remodeling processes in mouse models of intracranial internal carotid arteries (IICAs) and femoral arteries (FAs) following injury.
- To elucidate the unique pathophysiological characteristics of IICAs that may contribute to treatment complications.
Main Methods:
- Establishment of a novel vascular injury model in mouse IICAs.
- Comparative analysis of arterial remodeling, including neointimal hyperplasia, smooth muscle cell (SMC) behavior, re-endothelialization, and macrophage accumulation, between IICAs and FAs over 56 days.
Main Results:
- IICAs exhibited delayed neointimal hyperplasia (day 14-56) and continuous SMC loss in the media, leading to media extinction.
- Macrophage accumulation occurred in the adventitia of IICAs until day 56 and in the media by day 14.
- Re-endothelialization in IICAs was completed by day 28.
- Unique IICA findings include delayed neointima formation, media SMC loss, and adventitial growth compared to FAs.
Conclusions:
- Intracranial arteries demonstrate distinct pathophysiological remodeling patterns compared to peripheral arteries after injury.
- These unique features, such as SMC loss and delayed neointimal growth, may underlie the unfavorable outcomes observed with angioplasty and stenting in intracranial atherosclerotic diseases.
Abstract:
The effectiveness of angioplasty and stenting in intracranial atherosclerotic diseases is controversial due to high rates of delayed restenosis and hemorrhage compared with extracranial arteries. However, the mechanisms underlying these differences are still unclear, because their pathophysiology is yet to be examined. To address this issue, we established a novel vascular injury model in the intracranial internal carotid arteries (IICAs) in mice, and analyzed the remodeling process in comparison to that of the femoral arteries (FAs). In IICAs, neointimal hyperplasia was observed from day 14 and grew until day 56. Although smooth muscle cells (SMCs) emerged in the neointima from day 28, SMCs in the injured media were continuously lost with eventual extinction of the media. Re-endothelialization was started from day 7 and completed on day 28. Accumulation of macrophages was continued in the adventitia until day 56. Compared with FAs, the following points are unique in IICAs: (1) delayed continuous formation of neointima; (2) accumulation of macrophages in the media on day 14; (3) continuous loss of SMCs in the media followed by extinction of the media itself; and (4) continuously growing adventitia. These pathophysiologic differences might be associated with unfavorable outcomes in percutaneous transluminal angioplasty and stenting in intracranial arteries.
