Evidence of deregulated cholesterol efflux in abdominal aortic aneurysm

Mourmoura, Evanthia; Vasilaki, Anna; Giannoukas, Athanasios D.; Michalodimitrakis, Emmanouel; Pavlidis, Pavlos; Tsezou, Aspasia

doi:10.1016/j.acthis.2015.11.012

Cited by 13 publications

(6 citation statements)

References 39 publications

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“…We observed similarities in lipid deposition characteristics between PPE-induced AAA lesions and human lesions with both extracellularlylocated lipid and what seemed to be intracellularly-located lipid. This is consistent with a prior report showing extensive lipid accumulation in human AAA [49].…”

Section: Discussionsupporting

confidence: 94%

Hyperlipidemia does not affect development of elastase-induced abdominal aortic aneurysm in mice

et al. 2020

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Background and aims: Hyperlipidemia is a suggested risk factor for abdominal aortic aneurysm (AAA). However, whether hyperlipidemia is causally involved in AAA progression remains elusive. Here, we tested the hypothesis that hyperlipidemia aggravates AAA formation in the widely used porcine pancreatic elastase (PPE) model of AAA in mice with varying levels of plasma lipids. Methods: Prior to PPE-surgery, 8-week-old male C57BL/6J mice (n = 32) received 1⋅10 11 viral genomes of rAAV8-D377Y-mPcsk9 or control rAAV8 via the tail vein. Mice were fed either western type diet or regular chow. At baseline and during the 28 days following PPE-surgery, mice underwent weekly ultrasonic assessment of AAA progression. Experiments were repeated using Apolipoprotein E knockout (ApoE − /− ) mice (n = 7) and wildtype C57BL/6J mice (n = 5). Results: At sacrifice, maximal intergroup plasma cholesterol and non-HDL/HDL ratio differences were >5-fold and >20-fold, respectively. AAA diameters expanded to 150% of baseline, but no intergroup differences were detected. This was verified in an independent experiment comparing 8-week-old male ApoE − /− mice with wildtype mice. Histological evaluation of experimental AAA lesions revealed accumulated lipid in neointimal and medial layers, and analysis of human AAA lesions (n = 5) obtained from open repair showed medial lipid deposition. Conclusions: In summary, we find that lipid deposition in the aortic wall is a feature of PPE-induced AAA in mice as well as human AAA lesions. Despite, our data do not support the hypothesis that hyperlipidemia contributes to AAA progression.

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Section: Discussionsupporting

confidence: 94%

Hyperlipidemia does not affect development of elastase-induced abdominal aortic aneurysm in mice

et al. 2020

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“…ABCA1 mutation carriers are characterized by increased intima-media thickness [38,39], while ABCA1dependent cholesterol efflux is inversely correlated with pulse wave velocity in healthy subjects [40]. In addition, ABCA1 expression plays a critical regulatory role in VSMC differentiation and switch of VSMCs phenotype from contractile to synthetic form [12,41]. Recent studies also revealed that ABCA1 can function as an antiinflammatory receptor to suppress the expression of inflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

Elastic aortic wrap reduced aortic stiffness by partially alleviating the impairment of cholesterol efflux capacity in pigs

Liao

Zhou

Zhang

2018

J Diabetes Metab Disord

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Purpose Metabolic syndrome patients exhibit impaired cholesterol efflux capacity. Previous studies have shown a positive association between aortic stiffness and metabolic syndrome. However, it is unknown whether cholesterol efflux capacity participates in the process of aortic stiffness. This study sought to determine the effect of metabolic syndrome on aortic stiffening, and to investigate the effectiveness of aortic wraps on aortic compliance and the underlying mechanisms. Methods In a swine model of metabolic syndrome, we compared the cholesterol efflux capacity and aortic compliance responding to diet modifications and aortic wrap applications. Results Metabolic syndrome induced by high cholesterol diet significantly decreased cholesterol efflux capacity and aortic compliance. Elastic aortic wrap application increased aortic compliance and partially restored cholesterol efflux capacity via ATP binding cassette transporter A1 (ABCA1) pathway. Conclusions Cholesterol efflux plays a role in aortic stiffening. Elastic aortic wrap application could be a potential treatment for aortic stiffness related to metabolic syndrome.

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“…The importance of regulatory pathways in ABCA1 expression is critical in the regulation of VSMC differentiation, that is, a switch from a VSMC phenotype to a contractile synthetic form [ 77 , 78 ]. Apo A1 functions as the primary protein component of HDL and regulates the levels of ABCA1 by reducing the rate of ABCA1 protein degradation [ 79 ].…”

Section: The Role Of Abca1 In Influencing Cellular Phenotypesmentioning

confidence: 99%

Cholesterol Efflux: Does It Contribute to Aortic Stiffening?

Liao

McLachlan

2018

JCDD

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Aortic stiffness during cardiac contraction is defined by the rigidity of the aorta and the elastic resistance to deformation. Recent studies suggest that aortic stiffness may be associated with changes in cholesterol efflux in endothelial cells. This alteration in cholesterol efflux may directly affect endothelial function, extracellular matrix composition, and vascular smooth muscle cell function and behavior. These pathological changes favor an aortic stiffness phenotype. Among all of the proteins participating in the cholesterol efflux process, ATP binding cassette transporter A1 (ABCA1) appears to be the main contributor to arterial stiffness changes in terms of structural and cellular function. ABCA1 is also associated with vascular inflammation mediators implicated in aortic stiffness. The goal of this mini review is to provide a conceptual hypothesis of the recent advancements in the understanding of ABCA1 in cholesterol efflux and its role and association in the development of aortic stiffness, with a particular emphasis on the potential mechanisms and pathways involved.

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Evidence of deregulated cholesterol efflux in abdominal aortic aneurysm

Cited by 13 publications

References 39 publications

Hyperlipidemia does not affect development of elastase-induced abdominal aortic aneurysm in mice

Hyperlipidemia does not affect development of elastase-induced abdominal aortic aneurysm in mice

Elastic aortic wrap reduced aortic stiffness by partially alleviating the impairment of cholesterol efflux capacity in pigs

Cholesterol Efflux: Does It Contribute to Aortic Stiffening?

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