Animal models in atherosclerosis research☆

The chapter summarizes the rationale for the selection of non-human primates (NHPs) as animal models in biomedical and toxicologic research. The chapter contains an introduction to the subject matter followed by overviews of the use of the NHPs in research and contributions of NHP animal models to the understanding of and treatments for infectious and noninfectious diseases. Additionally, the challenges involved with NHP animal models and the current trends in the usage of NHPs are discussed.

Dietary fibres have diverse mechanisms in reducing plasma cholesterol, which could be useful for treating high levels of low-density lipoprotein cholesterol (LDL-C). The objective of this review is to determine the state of the evidence for the cholesterol-lowering effects of three selected fibres and their mechanisms, using the most recent animal trials. Therefore, a systematic review was conducted for hydroxypropyl methylcellulose (HPMC), pectin and chitosan in Pubmed, Embase and the Cochrane Library. All fibres reviewed reduced total cholesterol, very low-density lipoprotein cholesterol (VLDL-C) and LDL-C. Pectin gave a small, and chitosan an impressive rise in high-density lipoprotein cholesterol (HDL-C). A limitation of this study is the variety of animal models, each with distinct cholesterol profiles. Possible publication bias was also detected. In conclusion, chitosan seems to be the most promising of the studied fibres. A dietary fibre could be designed that yields the best cholesterol-lowering effect, using experiences in tailoring physicochemical properties and primarily exploiting the biophysical mechanisms of action.

Transforming growth factor-β and related growth factors are essential regulators for the development of follicles. Bone morphogenic protein (BMP) and activin membrane-bound inhibitor (BAMBI) was reported as a key factor participating in the transforming growth factor-β signal pathway. To investigate the role of BAMBI in porcine granulosa cells, the full length of the BAMBI was cloned from porcine ovarian cDNA. The results of bioinformatics analyses showed that the signaling peptide was located in between positions 20 and 21. The results of online prediction on phosphorylation sites indicate that the sites of Ser, Thr, and Tyr are 9, 1, and 1, respectively. In addition, BAMBI was highly homologous in rodent and livestock. Real-time quantitative polymerase chain reaction (qPCR) indicated that BAMBI was widely expressed in porcine tissues. Immunofluorescence showed that BAMBI was located in both nucleus and cytoplasm. Stimulating the granulosa cells with FSH in vitro could alter BAMBI expression level in a time-dependent manner. Moreover, the expression level declined after treatment with FSH. These results indicated that BAMBI is an FSH-repressed gene in porcine luteinizing granulosa cells and it may be involved in the regulation of ovarian follicle development and oocyte maturation.

The establishment of food preferences and aversions determines the modulation of eating behaviour and the optimization of food intake. These phenomena rely on the learning and memory abilities of the organism and depend on different psychobiological mechanisms such as associative conditionings and sociocultural influences. After summarizing the various behavioural and environmental determinants of the establishment of food preferences and aversions, this paper describes several issues encountered in human nutrition when preferences and aversions become detrimental to health: development of eating disorders and obesity, aversions and anorexia in chemotherapy-treated or elderly patients and poor palatability of medical substances and drugs. Most of the relevant biomedical research has been performed in rodent models, although this approach has severe limitations, especially in the nutritional field. Consequently, the final aim of this paper is to discuss the use of the pig model to investigate the behavioural and neurophysiological mechanisms underlying the establishment of food preferences and aversions by reviewing the literature supporting analogies at multiple levels (general physiology and anatomy, sensory sensitivity, digestive function, cognitive abilities, brain features) between pigs and humans.

A suitable animal model is required to investigate plaque biology. Here, we examined 6 rabbit models of plaque generated by balloon injury and sequential combinations of normal and high-cholesterol diets.

Fifty-eight male Japanese White rabbits were used. Lipid-rich macrophages accumulated in the center of the intima, and smooth muscle cells were located on the luminal side of the intima (similar to stable plaques in human coronary arteries) of a model in which balloon injury was followed by a normal diet for 4 weeks and then by a high-cholesterol diet for 4 weeks. Extending the high-cholesterol diet for a further 4 weeks increased accumulation of lipid-rich macrophages, diminished the amounts of elastic fibers and smooth muscle cells in the intima and caused the expression of matrix metalloproteinase-9 and tissue factor. All of these features are characteristic of unstable plaques. Moreover, quantitative analysis revealed that matrix metalloproteinase-9 expression and elastic-fiber content inversely correlated with statistical significance (R² = 0.52, p = 0.0003).

A high-cholesterol diet for 0 to 8 weeks after a normal diet for the first 4 weeks following balloon injury induced various arterial lesions resembling the diffuse intimal thickening, as well as stable and unstable plaques that accumulate in human coronary arteries. The present models might be useful for plaque studies.