Reduced M2 macrophages and adventitia collagen dampen the structural integrity of blood blister–like aneurysms and induce preoperative rerupture

Abstract

Objective Blood blister–like aneurysms (BBAs) are extremely rare aneurysms. They are predisposed to preoperative rerupture with a high case‐fatality rate. Here, we attempt to interrogate the distinct clinicopathology and the histological basis underlying its clinical rerupture. Methods Three middle meningeal arteries, 11 BBA (5 reruptured, 6 non‐rerupture) and 19 saccular aneurysm samples were obtained for histopathological investigation. Three reruptured BBAs, 3 non‐reruptured BBAs and 6 saccular (3 ruptured, 3 unruptured) aneurysms were obtained for quantitative flow cytometry analysis. Results Compared with true saccular aneurysms, the BBA aneurysm wall lacks arterial stroma cells including CD31+ endothelial cells and α‐SMA + smooth muscle cells. Only fibroblasts and adventitial collagen were observed in the BBA aneurysm wall. Meanwhile, BBAs were enriched with infiltrated inflammatory cells, especially polarized macrophages. Based on the rerupture status, those reruptured BBAs showed drastically reduced fibroblasts and adventitia collagen. Moreover, M2‐polarized macrophages were observed dominant in BBAs and exhibit repairing cellular functions based on their interplays with arterial fibroblasts. Reduced M2 macrophages and arterial tissue repairing modulation may be responsible for the decreasing collagen synthesis and fibrosis repairment, which potentially dampens the aneurysm integrity and induces BBA aneurysm reruputre. Conclusions BBAs poses histopathological features of occult pseudoaneurysms or dissecting aneurysms. Reduced M2 macrophages and adventitia collagen may dampen the structural integrity of BBAs and induce preoperative rerupture.

Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms

“…The loss of VSMC contractile properties but gaining of fibroblast features enables them to repair vascular injuries, so they are a reckoned hallmark of aneurysmal and atherosclerotic lesions in the central and peripheral arterial systems (43)(44)(45). This supports the view by some investigators that the arterial wall is fragile and thin and that only a single layer of fibrous connective tissue plaque is present before the rupture of the aneurysm because the VSMCs have become necrotic or mineralized during the long-term atherosclerotic process, and the residual mural cell component is already very scarce (16,20,34,46). Another important finding is the prominent role of secreted phosphoprotein 1 (SPP1) (also known as osteopontin, OPN) and SPP1-associated molecular pathways.…”

“…We previously provided flow cytometry evidence to show the chronic arterial inflammation process in BBAs. We described an elevated percentage of M2 macrophages in previous flow cytometry studies (20). Nonetheless, the oversimplified classification of M1 and M2 already failed to serve the multifaced research purpose.…”

“…According to the description by McLaughlin, the imaging presentation can vary into four subtypes in clinical situations, but a common feature they all share is the aberrant occurrence on the non-bifurcated part of the ICA (18,19). Our previous studies have explored the immune-histological features of BBAs and demonstrated that BBA is not simply a thrombotic dissecting aneurysm but also with large numbers of infiltrated macrophages (16,20). However, much of the BBA research, including ours, have been descriptive in nature; the etiology of BBA is still an unresolved cerebrovascular enigma (10,21).…”

The Effect of N6-Methyladenosine Regulators and m6A Reader YTHDC1-Mediated N6-Methyladenosine Modification Is Involved in Oxidative Stress in Human Aortic Dissection

“…Thrombospondin 1, which can be induced by angiotensin II, is markedly elevated in AD patients and may be involved in AD by promoting M1 macrophage planning and vascular smooth muscle apoptosis [61,62]. M2 macrophages act as a protective factor with phenotype repair cell function in the study of blood blister-like aneurysms [63]. Macrophages may not only participate in the onset of AD but also in the repair of AD.…”

Peripheral macrophages in the development and progression of structural cerebrovascular pathologies

“…This concept is supported by the observation that reduced M2 macrophage levels correlate with impaired IA structural integrity. 145 An anabolic/ catabolic-like inflammatory balance in quiescent IAs could prevent enlargement and progression towards rupture, and disturbances of this balance may lead to wall weakening and hemorrhage. Ultimately, the M1/M2 classification system represents an oversimplification in IAs as it does in other conditions.…”