A severe atherosclerosis mouse model on the resistant NOD background

Wang, Xugang; Huang, Rong; Zhang, Lichen; Li, Saichao; Luo, Jing; Gu, Yanrong; Chen, Zhijun; Qin, Zheng; Chao, Tianzhu; Zheng, Wenping; Qi, Xinhui; Wang, Li; Wen, Yinhang; Liang, Yinming; Lu, Liaoxun

doi:10.1242/dmm.033852

Cited by 21 publications

(23 citation statements)

References 41 publications

(50 reference statements)

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“…Already now most studies are using tissue-specific overexpression or knockout mouse models, but also starting to address the function of specific mutations and not yet well-described posttranslational protein modifications, such as SUMOylation, in atherogenesis and cardiovascular diseases (66–70). Moreover, the incredibly fast development of the Crispr/Cas9 system led to the development of new mouse and also larger animal models to study atherogenesis and will continue to accelerate basic and translational cardiovascular research (71–76).…”

Section: Perspectivementioning

confidence: 99%

Mouse Models for Atherosclerosis Research—Which Is My Line?

Oppi

Lüscher

Stein

2019

Front. Cardiovasc. Med.

132

125

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Atherosclerosis is one of the primary causes of cardiovascular disease and mortality. This chronic immunometabolic disease evolves during decades in humans and encompasses different organs and immune cell types, as well as local and systemic processes that promote the progression of the disease. The most frequently used animal model to study these atherogenic processes and inter-organ crosstalk in a short time frame are genetically modified mouse models. Some models have been used throughout the last decades, and some others been developed recently. These models have important differences in cholesterol and lipoprotein metabolism, reverse cholesterol transport pathway, obesity and diabetes as well as inflammatory processes. Therefore, the disease develops and progresses differently in the various mouse models. Since atherosclerosis is a multifaceted disease and many processes contribute to its progression, the choice of the right mouse model is important to study specific aspects of the disease. We will describe the different mouse models and provide a roadmap to facilitate current and future atherosclerosis researchers to choose the right model depending on their scientific question.

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Section: Perspectivementioning

confidence: 99%

Mouse Models for Atherosclerosis Research—Which Is My Line?

Oppi

Lüscher

Stein

2019

Front. Cardiovasc. Med.

132

125

View full text Add to dashboard Cite

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“…Oxidative stress markers are a series of biochemical substances that reflect oxidative stress levels in vivo (17). There are various types of oxidative stress markers.…”

Section: Discussionmentioning

confidence: 99%

“…There are various types of oxidative stress markers. Of them, ROS, reactive nitrogen species and lipid peroxide are commonly used in diabetes detection (17). Determination of oxidative stress markers serves an important role in revealing correlations of diabetes genesis and development with oxidative stress (17).…”

Section: Discussionmentioning

confidence: 99%

“…Of them, ROS, reactive nitrogen species and lipid peroxide are commonly used in diabetes detection (17). Determination of oxidative stress markers serves an important role in revealing correlations of diabetes genesis and development with oxidative stress (17). In the present study, it was observed that miR-214 overexpression decreased oxidative stress in the in vitro DN model.…”

Section: Discussionmentioning

confidence: 99%

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miRNA‑214 suppresses oxidative stress in diabetic nephropathy via the ROS/Akt/mTOR signaling pathway and uncoupling protein 2

Yang

Fei

et al. 2019

Exp Ther Med

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In the present study, the function of microRNA (miR)-214 on diabetic nephropathy (DN) and diabetes of proximal tubular cells was investigated. Reverse transcription-quantitative polymerase chain reaction was used measure the expression of miR-214 in rats with DN and ELISA was performed to measure oxidative stress and ROS levels. Results indicated that miR-214 expression in the peripheral blood was significantly decreased in rats with DN. The in vitro model of DN indicated that miR-214 upregulation significantly decreased oxidative stress and reactive oxygen species (ROS) levels, but significantly increased uncoupling protein 2 (UCP2), phosphorylated (p)-Akt and p-mammalian target of rapamycin (mTOR) protein expression levels. The administration of genipin, a UCP2 inhibitor, significantly attenuated the effects of miR-214 upregulation on oxidative stress in the in vitro DN model by regulating ROS, Akt and mTOR protein expression levels. Notably, Akt inhibitor suppressed p-Akt protein expression and attenuated the effects of miR-214 upregulation on oxidative stress in the in vitro DN model. Collectively, these data suggest that miR-214 regulates diabetes through a ROS/Akt/mTOR signaling pathway by UCP2 in proximal tubular cells.

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“…By contrast, C57BL/6 mice with the ApoE deficiency developed the disease when fed with a high-fat diet. Moreover, simultaneous knockdown of both ldlr and apoE resulted in a severe atherosclerosis [14].…”

Section: Introductionmentioning

confidence: 99%

In Search for Genes Related to Atherosclerosis and Dyslipidemia Using Animal Models

Poznyak

Grechko

Wetzker

et al. 2020

IJMS

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Atherosclerosis is a multifactorial chronic disease that affects large arteries and may lead to fatal consequences. According to current understanding, inflammation and lipid accumulation are the two key mechanisms of atherosclerosis development. Animal models based on genetically modified mice have been developed to investigate these aspects. One such model is low-density lipoprotein (LDL) receptor knockout (KO) mice (ldlr −/− ), which are characterized by a moderate increase of plasma LDL cholesterol levels. Another widely used genetically modified mouse strain is apolipoprotein-E KO mice (apoE −/− ) that lacks the primary lipoprotein required for the uptake of lipoproteins through the hepatic receptors, leading to even greater plasma cholesterol increase than in ldlr −/− mice. These and other animal models allowed for conducting genetic studies, such as genome-wide association studies, microarrays, and genotyping methods, which helped identifying more than 100 mutations that contribute to atherosclerosis development. However, translation of the results obtained in animal models for human situations was slow and challenging. At the same time, genetic studies conducted in humans were limited by low sample sizes and high heterogeneity in predictive subclinical phenotypes. In this review, we summarize the current knowledge on the use of KO mice for identification of genes implicated in atherosclerosis and provide a list of genes involved in atherosclerosis-associated inflammatory pathways and their brief characteristics. Moreover, we discuss the approaches for candidate gene search in animals and humans and discuss the progress made in the field of epigenetic studies that appear to be promising for identification of novel biomarkers and therapeutic targets.challenge is the lack of effective treatment approaches, which is the consequence of our incomplete understanding of the processes that underlie the pathogenesis. Genetic base is one of the most important features that are involved in the disease development.Currently, the most widely used anti-atherosclerosis drugs are statins [3]. The aim of statin therapy is reducing the blood level of low-density lipoprotein (LDL) cholesterol, which is a well-known pro-atherogenic agent. It was demonstrated that statin therapy reduces the risk of cardiovascular events by approximately one third [4]. However, statin therapy alone cannot be regarded as effective treatment of atherosclerosis. Increasing the plasma levels of high-density lipoprotein (HDL), which has anti-atherogenic properties, is another promising approach. Accumulating evidence shows that high levels of HDL cholesterol can inhibit atherosclerosis progression. To date, several therapeutic agents that increase HDL levels are known, including niacin, fibrates, and statins. Among the recently developed medications are apoA-I-phospholipid complexes, human apoA-I and apoA-I-mimetic peptides, and inhibitors of cholesterol ester transfer protein, which have reached the level of clinical trials. However, the inhibitor ...

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A severe atherosclerosis mouse model on the resistant NOD background

Cited by 21 publications

References 41 publications

Mouse Models for Atherosclerosis Research—Which Is My Line?

Mouse Models for Atherosclerosis Research—Which Is My Line?

miRNA‑214 suppresses oxidative stress in diabetic nephropathy via the ROS/Akt/mTOR signaling pathway and uncoupling protein 2

In Search for Genes Related to Atherosclerosis and Dyslipidemia Using Animal Models

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