Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture

Ollikainen, Eliisa; Tulamo, Riikka; Lehti, Satu; Lee-Rueckert, Miriam; Hernesniemi, Juha; Niemelä, Mika; Ylä‐Herttuala, Seppo; Kovanen, Petri T.; Frösén, Juhana

doi:10.1093/jnen/nlw041

Cited by 66 publications

(53 citation statements)

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“…Oxidized lipids can induce chronic inflammation in atherosclerotic lesion, which is characterized by infiltration of macrophages as in ruptured aneurysm wall. Recent research has also implicated lipid accumulation as a key factor in promoting degeneration of the aneurysm wall via formation of foam cells and subsequent loss of mural cells (10,11). In our study, higher LDL infiltration rate was observed in the ruptured aneurysm wall, implicating lipid accumulation in ruptured aneurysms, which is consistent with the above researches.…”

Section: Discussionsupporting

confidence: 92%

“…For example, patients having a high lipid level or high blood pressure does not necessarily indicate a high lipid accumulation in the aneurysm wall and vice versa. LDL, though widely recognized as risk factors for cardiovascular and cerebrovascular disease, was not found to be associated with cerebral aneurysm rupture in a recent clinical study (12), which seems to conflict with findings from a histopathology study (9,10). However, it is important to note that despite LDL not recognized as a risk factor, the use of a lipidlowering agent was found to be able to reduce the risk of rupture (12).…”

Section: Discussionmentioning

confidence: 90%

“…Morphological and hemodynamic parameters have been shown to be associated with aneurysm rupture (2-7), yet there is still debate on the role of wall shear stress in aneurysm rupture (8). It has also been shown that aneurysm wall degradation is associated with lipid accumulation (9)(10)(11) and the use of a lipid-lowering agent can reduce the risk of rupture (12). As aneurysm wall degradation is closely related to lipid accumulation, evaluating lipid accumulation in aneurysmal wall might provide extra information for rupture prediction.…”

Section: Introductionmentioning

confidence: 99%

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Elevated Lipid Infiltration Is Associated With Cerebral Aneurysm Rupture

Qian

Zhang

et al. 2020

Front. Neurol.

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Background: Intracranial aneurysm wall degradation can be associated with lipid infiltration. However, the relationship between lipid infiltration and aneurysm rupture has not been explored quantitatively. To investigate the correlation between lipid infiltration and aneurysm rupture, we utilized patient-specific simulation of low-density lipoprotein (LDL) transport to analyze lipid infiltration in the cerebral aneurysm wall. Methods: Sixty-two aneurysms were analyzed. Patient blood pressure, plasma LDL concentration, and three-dimensional angiographic images were obtained to simulate LDL transport in aneurysms. Morphological, hemodynamic, and lipid accumulation parameters were compared between ruptures and unruptured groups. Multivariate logistic regression was also performed to determine parameters that are independently associated with rupture. Results: Size ratio, wall shear stress, low shear area, relative residence time, area-averaged LDL infiltration rate, and maximum LDL infiltration rate were significant parameters in univariate analysis (P < 0.05). Multivariate analysis revealed that only average LDL infiltration remained as a significant variable (P < 0.05). The prediction model derived showed good performance for rupture prediction (AUC, 0.885; 95% CI, 0.794-0.976). Conclusions: Ruptured aneurysms showed significantly higher LDL infiltration compared to unruptured ones. Our results suggested that lipid infiltration may promote aneurysm rupture. Lipid infiltration characteristics should be considered when assessing aneurysm rupture risk.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Elevated Lipid Infiltration Is Associated With Cerebral Aneurysm Rupture

Qian

Zhang

et al. 2020

Front. Neurol.

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“…52 Clinically, one of the most pertinent questions regarding the biology of aneurysm formation is how to stabilize small inceptions of aneurysms or small aneurysms and prevent them from growing to a size in which rupture becomes increasingly likely. 22,31,72 The presence of MCP1 expression and macrophages 9,27,34,55 in human IA walls implies that the same molecular mechanisms as in IA initiation might be involved in IA progression, at least in the formation of daughter aneurysms or so-called "secondary pouches" that tend to form in the IA sacs at regions with high WSS. 15 In addition to high-WSS areas, MCP1 can be also induced in IA regions with low WSS.…”

Section: Flow-triggered Inflammation-mediated Remodeling In Aneurysm mentioning

confidence: 99%

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms

Frösén

Cebral

Robertson

et al. 2019

Neurosurgical Focus

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215

162

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OBJECTIVEUnruptured intracranial aneurysms (UIAs) are relatively common lesions that may cause devastating intracranial hemorrhage, thus producing considerable suffering and anxiety in those affected by the disease or an increased likelihood of developing it. Advances in the knowledge of the pathobiology behind intracranial aneurysm (IA) formation, progression, and rupture have led to preclinical testing of drug therapies that would prevent IA formation or progression. In parallel, novel biologically based diagnostic tools to estimate rupture risk are approaching clinical use. Arterial wall remodeling, triggered by flow and intramural stresses and mediated by inflammation, is relevant to both.METHODSThis review discusses the basis of flow-driven vessel remodeling and translates that knowledge to the observations made on the mechanisms of IA initiation and progression on studies using animal models of induced IA formation, study of human IA tissue samples, and study of patient-derived computational fluid dynamics models.RESULTSBlood flow conditions leading to high wall shear stress (WSS) activate proinflammatory signaling in endothelial cells that recruits macrophages to the site exposed to high WSS, especially through macrophage chemoattractant protein 1 (MCP1). This macrophage infiltration leads to protease expression, which disrupts the internal elastic lamina and collagen matrix, leading to focal outward bulging of the wall and IA initiation. For the IA to grow, collagen remodeling and smooth muscle cell (SMC) proliferation are essential, because the fact that collagen does not distend much prevents the passive dilation of a focal weakness to a sizable IA. Chronic macrophage infiltration of the IA wall promotes this SMC-mediated growth and is a potential target for drug therapy. Once the IA wall grows, it is subjected to changes in wall tension and flow conditions as a result of the change in geometry and has to remodel accordingly to avoid rupture. Flow affects this remodeling process.CONCLUSIONSFlow triggers an inflammatory reaction that predisposes the arterial wall to IA initiation and growth and affects the associated remodeling of the UIA wall. This chronic inflammation is a putative target for drug therapy that would stabilize UIAs or prevent UIA formation. Moreover, once this coupling between IA wall remodeling and flow is understood, data from patient-specific flow models can be gathered as part of the diagnostic workup and utilized to improve risk assessment for UIA initiation, progression, and eventual rupture.

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“…It is a major health care concern since the rupture of an aneurysm can lead to subarachnoid hemorrhage, placing the patient in great danger [2,3]. It has been suggested that the occurrence, development, and even rupture of aneurysms are mainly caused by hemodynamic factors [4].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Placing Flow-Diverting Stents in Intracranial Collateral Arteries of Miniature Pig

Wang

Ding

Wang³

et al. 2017

Med Sci Monit

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BackgroundFlow-diverting stent (FDS) has been suggested as an effective intracranial aneurysm treatment. However, the effects of FDS on collateral branches of an aneurysm parent artery still remain unknown. Thus, the present study aimed to comprehensively evaluate the effects of placing a FDS in the intracranial collateral artery, using a miniature pig animal model.Material/MethodsTen healthy miniature pigs were included in the study: one pig was reserved as a control and the remaining nine pigs were placed in three experimental groups: FDS (i.e., Pipeline), LVIS, and Solitaier-AB stent groups. Pigs in the experimental groups were examined by cerebral angiography immediately after stent placement, followed by hemodynamic analyses. In addition, magnetic resonance imaging (MRI) of the brain of pigs in the experimental groups was performed to inspect the brain for obstruction and blood flow. Stents were examined for the growth of neointimas.ResultsThe results showed that neointimas, consisting of smooth muscle cells, collagenous fibers, and macrophages, were 0.67 mm thick on average and partially covered the stent wires. The thickness of neointimas in the FDS group was significantly higher than in the two conventional intracranial stent groups. There was no obvious obstruction identified in collateral arteries where the FDS was placed.ConclusionsThese results indicated that neointimas in collateral arteries of a miniature pig would be slightly thickened after one month of FDS placement; and FDS was shown to be safe for collateral arteries.

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Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture

Cited by 66 publications

References 50 publications

Elevated Lipid Infiltration Is Associated With Cerebral Aneurysm Rupture

Elevated Lipid Infiltration Is Associated With Cerebral Aneurysm Rupture

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms

The Effect of Placing Flow-Diverting Stents in Intracranial Collateral Arteries of Miniature Pig

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