Hyperlipidemia models

The role of RANTES has been further elucidated through the use of mouse models via three approaches (i) induction of hyperlipidemia with a high-fat... 

CASE EXAMPLE TRANSGENIC HUMANIZED MOUSE MODELS FOR HYPERLIPIDEMIA... 

Cardiovascular disease models demonstrate aspects/features of humanized disease models. For hyperlipidemia-based atherosclerosis, there is a lack of a spontaneous in vivo mouse model because mice are resistant to (diet-induced) hyperlipidemia. Therefore a number of transgenic mice have been developed to better understand the pathogenesis in humans and obtain mouse models predictive of the human disease. Overexpression of ApoB, ApoE-variants, and knockout of ApoE, the LDL receptor or LPL (lipopro-... 

Huang Y. Transgenic and gene-targeted mice in the study of hyperlipidemia. In Xu Q, ed. A Handbook of Mouse Models of Cardiovascular Disease. New York Wiley, 2006 33-41. 

Jurgonski, A., Juskiewicz, J. Zdunczyk, Z. 2008. Ingestion of black chokeberry fruit extract leads to intestinal and systemic changes in a rat model of prediabetes and hyperlipidemia. Plant Foods Hum. Nutr. 63 176-182. 

Kasiske BL, O Donnell MP, Keane WE. The Zucker rat model of obesity, insulin resistance, hyperlipidemia, and renal injury. Hypertension 1992 19(1 suppl) 1110-5. 

Exchangeable apolipoproteins are a class of functionally important proteins which play a key role in plasma lipoprotein metabolism. In this capacity they have been associated with several human disorders, including hyperlipidemia and cardiovascular disease (1,2). Apolipophorin-III (apoLp-III) is a model exchangeable apolipoprotein derived from the insect Manr/Mca sexta (166 residues, Mr 18,380). ApoLp-III is a major hemolymph protein in the adult life stage and... 

Hyperlipidemia and the recruitment of inflammatory cells into the atherosclerotic arterial wall are suggested to cause excessive production of oxygen flee radicals [19]. Ohara et al. found that aortas from rabbits that had been fed a high cholesterol diet for several weeks produced several fold more oxygen free radicals than did control aortas [19,24]. Furthermore, removal of the endothelium resulted in reduction of free radical production, suggesting that the endothelium is a major source of the reactive oxygen species in this model. It was hypothesized that the abnormal redox state in the arterial wall may be a fundamental metabolic feature of atherosclerosis [19]. 

Pharmacogenomic studies have been performed on a range of different cultured cells that participate in the formation of atherosclerotic lesion including ECs, SMCs, monocytes, and macrophages [144], as well as animal models [145], atherosclerotic lesion samples and blood-derived cells from patients with hyperlipidemia or coronary artery disease [144], Representative examples of such studies and their contribution towards improving atheroprotective treatments are presented in the following sections. 

Accumulating evidence for important functions of enzymes involved in lipid synthesis and its control has been obtained through targeted disruption in rodent models of the corresponding genes (Fig. 11.2). However, direct links between abnormal expression or genetic variants and human disorders, such as obesity, hyperlipidemia, insulin resistance, and NIDDM await further clarification. Glycerol-... 

Although the data are not conclusive, hyperlipidemia has been associated as a susceptibility factor for CKD in both animal and human studies. The use of lipid-lowering agents in some animal models has been found to decrease the extent of glomerular injury when both underlying renal disease and hyperlipidemia are present. Therefore the correction of lipid abnormalities in patients with CKD was proposed to have a beneficial effect on the rate of progression of the disease. CKD with or without nephrotic syndrome is frequently accompanied by abnormalities in fipoprotem metabolism. The prevalence of hyperlipidemia appears to increase as kidney function declines and with the presence of the nephrotic syndrome. ... 

However, it must be said that most of the literature considered in this chapter refers to experimental work performed with cell lines or in vivo by means of rodent models. Both PPARot and SREBP-lc are very attractive drug targets. Therefore, it would be of crucial interest to document their respective gender and species-specificity. PPARot activators such as fibrates are currently widely prescribed drugs for human hyperlipidemia. To our knowledge, there is no current use of drugs targeting SREBPlc. 

Escola-Gil, J. C., O. Jorba, J. Julve-Gil, F. Gonzalez-Sastre, J. Ordonez-Llanos, and F. Blanco-Vaca. 1999. Pitfalls of direct HDL-cholesterol measurements in mouse models of hyperlipidemia and atherosclerosis. Clinical Chemistry 45 1567-1569. 

During recent years, great efforts have been made to control experimentally induced hyperlipidemia and atheromatosis in animals. Although much energy has been spent on these studies, they have limited application to man and are best regarded as model systems for pharmacological, nutritional and other investigations. 

Animal model studies suggest that a high fructose diet, mainly as part of sucrose or high-fructose com s)Tup (a key additive in processed foods, soft drinks and other beverages), has been associated with insulin resistance, impaired glucose tolerance, hyperlipidemia and hypertension, as reviewed by Elliott et al. in 2002. However,... 

Increased level of reactive oxygen speeies (ROS) has been found to induce various physiologieal disorders. Among these health problems, cardiovascular diseases are linked to exeessive generation of ROS that cause oxidative stress. Elevated levels of vascular superoxide anion production have been foimd in animal models of hyperlipidemia [90,91], h5 ertension [92,93], and diabetes [94,95]. Furthermore, clinical studies have established that h ercholesterolemia and diabetes in... 

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