Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normolipidemic humans.

Grass, David; Saini, Urmil; Felkner, Roland H.; Wallace, Racheal; Lago, William J. P.; Young, Stephen G.; Swanson, Mark E.

doi:10.1016/s0022-2275(20)39866-7

Cited by 56 publications

(14 citation statements)

References 30 publications

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“…Compound 26 also dose-dependently elevated HDL-cholesterol up to +37% and reduced LDL-cholesterol down to −60% in hCETP/hApoB-100 transgenic mice at doses of 10 mg/kg (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives

Trieselmann¹,

Wagner²,

Fuchs³

et al. 2014

J. Med. Chem.

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A series of 1,1'-spiro-substituted hexahydrofuroquinoline derivatives exhibiting potent cholesteryl ester transfer protein (CETP) inhibition at reduced lipophilicity was identified. A focused structure-activity relationship (SAR) exploration led to the potent and comparatively polar CETP inhibitor 26 showing robust high density lipoprotein-cholesterol (HDL-C) elevation and low density lipoprotein-cholesterol (LDL-C) reduction in transgenic hCETP/hApoB-100 mice. Compound 26 was also shown to positively differentiate from highly lipophilic CETP inhibitors in its complete elimination from fat tissue in hCETP transgenic mice as evident within 21 days after cessation of treatment. In addition, compound 26 showed no significant effects on aldosterone secretion from H295R cells, as well as no significant effects on blood pressure and electrocardiogram parameters in telemetrized cynomolgus monkeys.

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“…Compound 26 also dose-dependently elevated HDL-cholesterol up to +37% and reduced LDL-cholesterol down to −60% in hCETP/hApoB-100 transgenic mice at doses of 10 mg/kg (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives

Trieselmann¹,

Wagner²,

Fuchs³

et al. 2014

J. Med. Chem.

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“…114 Co-expressing human APOB with CETP as transgenes in mice results in a human-like lipoprotein profile. 49 These results support the notion that CETP could be a therapeutic target, but the specific CETP-inhibitors that were developed did not show sufficient benefit in large-scale clinical trials to justify clinical use. 115 This has somewhat reduced the interest in using human CETP -transgenics as experimental atherosclerosis models; however, CETP transgenic mice have been crossed with both APOB transgenics and APOE3-Leiden mice.…”

Section: Humanized Models Of Atherosclerosis Lipoprotein Metabolism A...mentioning

confidence: 59%

Animal Models of Atherosclerosis–Supportive Notes and Tricks of the Trade

Gisterå

Ketelhuth

Malin

et al. 2022

Circulation Research

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Atherosclerotic cardiovascular disease is a major cause of death among humans. Animal models have shown that cholesterol and inflammation are causatively involved in the disease process. Apolipoprotein B-containing lipoproteins elicit immune reactions and instigate inflammation in the vessel wall. Still, a treatment that is specific to vascular inflammation is lacking, which motivates continued in vivo investigations of the immune-vascular interactions that drive the disease. In this review, we distill old notions with emerging concepts into a contemporary understanding of vascular disease models. Pros and cons of different models are listed and the complex integrative interplay between cholesterol homeostasis, immune activation, and adaptations of the vascular system is discussed. Key limitations with atherosclerosis models are highlighted, and we suggest improvements that could accelerate progress in the field. However, excessively rigid experimental guidelines or limiting usage to certain animal models can be counterproductive. Continued work in improved models, as well as the development of new models, should be of great value in research and could aid the development of cardiovascular disease diagnostics and therapeutics of the future.

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“…To test whether the lack of HDL decrease with LPL deficiency was due to the absence of CETP in mice, HuB were bred with human CETP transgenic mice (21). Although CETP reduced HDL and increased IDL/LDL in HuB mice (26), the lipoprotein profile created was still dissimi-lar to that found in humans and especially humans with combined hyperlipidemia. To create a partial defect in VLDL catabolism along with the CETP-mediated changes in HDL, HuB/CETP mice were crossed with LPL1 mice.…”

Section: Lipoproteins In Hub/lpl1/cetp Micementioning

confidence: 99%

Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice

Kako

Massé

Huang

et al. 2002

Journal of Lipid Research

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Both hyperglycemia and hyperlipidemia have been postulated to increase atherosclerosis in patients with diabetes mellitus. To study the effects of diabetes on lipoprotein profiles and atherosclerosis in a rodent model, we crossed mice that express human apolipoprotein B (HuB), mice that have a heterozygous deletion of lipoprotein lipase (LPL1), and transgenic mice expressing human cholesteryl ester transfer protein (CETP). Lipoprotein profiles due to each genetic modification were assessed while mice were consuming a Western type diet. Fast-protein liquid chromatography analysis of plasma samples showed that HuB/ LPL1 mice had increased VLDL triglyceride, and HuB/ LPL1/CETP mice had decreased HDL and increased VLDL and IDL/LDL. All strains of mice were made diabetic using streptozotocin (STZ); diabetes did not alter lipid profiles or atherosclerosis in HuB or HuB/LPL1/CETP mice.In contrast, STZ-treated HuB/LPL1 mice were more diabetic, severely hyperlipidemic due to increased cholesterol and triglyceride in VLDL and IDL/LDL, and had more atherosclerosis. -

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Transgenic mice expressing both human apolipoprotein B and human CETP have a lipoprotein cholesterol distribution similar to that of normolipidemic humans.

Cited by 56 publications

References 30 publications

Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives

Potent Cholesteryl Ester Transfer Protein Inhibitors of Reduced Lipophilicity: 1,1′-Spiro-Substituted Hexahydrofuroquinoline Derivatives

Animal Models of Atherosclerosis–Supportive Notes and Tricks of the Trade

Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice

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