Ocular Phenotype of Mice with Impaired Fibrillin-1 Function on Hypercholesterolemic Apolipoprotein E-Deficient Background

Aim: Transgenic mice with an elastic fiber mutation (C1039G+/-) in the fibrillin-1 gene and apolipoprotein E deficiency express vulnerable atherosclerotic plaque formation in the aorta and coronary and carotid arteries. The fibrillin-1 gene mutation alone leads to impaired fibrillin-1 function common to Marfan syndrome. The aim was to study for the first time the potential effects of atherosclerosis and vulnerable plaques in mouse eye and spontaneous retinal vessel occlusions in these mice.Methods: Apolipoprotein E-deficient and fibrillin-1 mutated mice (ApoE-/-/Fbn1C1039G+/-) were used for the study. ApoE-/- littermates served as controls. Optical coherence tomography and fluorescein angiography were used to study the retina and retinal vessels before and after the 12-week high-fat diet. Series of staining were performed to study morphology, apoptosis, glial fibrillary acidic protein activation, collagen formation, inflammatory cell infiltration and drusen formation.Results: No pathological changes were found in hypercholesterolemic ApoE-/-/Fbn1C1039G+/- mice in imaging studies nor in the histological stainings. There was neither abnormality in the retinal morphology nor any detectable biomarkers.Conclusion: ApoE-/-/Fbn1C1039G+/- mice did not present the ocular signs of Marfan syndrome.12-week high-fat diet is not sufficient to induce retinal vessel occlusion on 20 to 23 weeks old mice. This indicates that the mechanistic background of retinal vessel occlusion is more complex.

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Effects of atorvastatin and/or probucol on recovery of atherosclerosis in high-fat-diet-fed apolipoprotein E–deficient mice

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.10.184 ◽

2019 ◽

Vol 109 ◽

pp. 1445-1453 ◽

Cited By ~ 4

Author(s):

Xiaokun Guo ◽

Lin Wang ◽

Xiaoshuang Xia ◽

Peilu Wang ◽

Xin Li

Keyword(s):

Apolipoprotein E ◽

High Fat Diet ◽

High Fat ◽

Deficient Mice

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Androgen Receptor-Dependent and Independent Atheroprotection by Testosterone in Male Mice

Endocrinology ◽

10.1210/en.2010-0663 ◽

2010 ◽

Vol 151 (11) ◽

pp. 5428-5437 ◽

Cited By ~ 58

Author(s):

Johan Bourghardt ◽

Anna S. K. Wilhelmson ◽

Camilla Alexanderson ◽

Karel De Gendt ◽

Guido Verhoeven ◽

...

Keyword(s):

Androgen Receptor ◽

Apolipoprotein E ◽

High Fat Diet ◽

Atherosclerotic Lesion ◽

Male Mice ◽

Wild Type ◽

High Fat ◽

Lesion Area ◽

Major Pathway

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.

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