G&amp;ouml;ttingen Miniature Swine as a Model for Diet-induced Atherosclerosis

Tanigawa, Manabu; Akaike, Isamu; Adachi, Jiro; Shinkai, Hiroshi; Tokoi, Kazuo; Uchiyama, Tomoharu; IBARAKI, Teisuke; Mochizuki, Kiyofumi

doi:10.1538/expanim1978.35.1_47

Cited by 7 publications

(6 citation statements)

References 7 publications

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“…In all animals, increased levels of lipid parameters such as T-Cho, HDL and LDL, and lipid deposition in organs and tissues as demonstrated by areas of yellow-white discoloration and raised plaques on the inner surface of many arteries, whitish-yellow livers, pale red spleens, fatty change of hepatocytes, aggregations of foamy Kupffer cells in liver sinusoid, and aggregations of foamy cells in red pulps were observed. These changes are considered a consequence of feeding a high-cholesterol diet for a given period of time [22] and ensured that all animals had features sufficient to be a model for atherosclerosis. In addition, increased levels of GGT were found in all animals, which were deemed secondary effects due to lipid deposition in organs or progression of atherosclerotic lesions [22].…”

Section: Discussionmentioning

confidence: 99%

“…There should be a variety of risk factors which have to be validated before safe and universal application of G-CSF to patients with cardiovascular system disorders. The present study was carried out to evaluate the effects of G-CSF on atherosclerotic lesions, using a miniature swine atherosclerosis model which has been reported to exhibit similarities to human in the distributions and properties of atherosclerotic lesions [22]. In addition, the general toxicological effects of G-CSF on this model were also evaluated.…”

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confidence: 99%

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Granulocyte Colony-Stimulating Factor Has No Adverse Effects on Atherosclerotic Lesions in High Cholesterol-Fed Miniature Swine

Takai

Miyoshi

Yamazaki

et al. 2008

The Journal of Veterinary Medical Science

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Granulocyte colony-stimulating factor (G-CSF) is widely used to mobilize peripheral blood stem cells, and expected to restore cardiac function for patients with coronary artery diseases as a consequence of progression of atherosclerosis. Safety issues related to the administration of G-CSF to these patients, however, are still under study. The animal model for atherosclerosis was produced by feeding miniature swine a high-cholesterol diet for 3 months. G-CSF (5 or 10 microg/kg/day) was given to the animal model by daily subcutaneous injections for 10 days and 20 main arteries were evaluated pathologically. In addition, the general toxicological effects were studied on clinical signs, body weight, hematology, blood chemistry and pathology. In the G-CSF-treated groups, a variety of changes related to the major pharmacological activity of G-CSF including an increase in white blood cell (WBC) counts were observed. In many arteries, atherosclerotic lesions similar to Type I-V of the proposed classification by the American Heart Association were observed. No effects of the G-CSF treatment were seen on the histopathological findings, incidence, severity or distribution of atherosclerotic lesions. In addition, no infiltration of neutrophils to the lesions was observed. These findings suggest that the administration of G-CSF causes neither exacerbation or modification of atherosclerotic lesions nor adverse changes despite that a sufficient increase in WBC counts could be achieved in the peripheral blood.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Granulocyte Colony-Stimulating Factor Has No Adverse Effects on Atherosclerotic Lesions in High Cholesterol-Fed Miniature Swine

Takai

Miyoshi

Yamazaki

et al. 2008

The Journal of Veterinary Medical Science

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“…However, our results of differential monocytic cell adhesion in both the canine and porcine aortas do reflect the distribution of atherosclerosis seen in both spe cies. While the development of atherosclerotic lesions is exceedingly rare in normal dogs, dogs treated with thiouracil and fed high cholesterol diets develop arterial lesions with similar morphology to humans and in similar anatomic location, predominantly the distal aorta, and the iliac, femoral, and coronary arteries [41], Pigs fed only a moderately high fat, high cholesterol diet also develop atherosclerotic lesions similar in location and morphology to humans, consisting of fatty streaks in the thoracic aorta and fibrous plaques in the distal aorta [42], The regional specificity of monocytic cell adhesion and its correlation to the location of atherosclerotic lesions suggests a possi ble causal relationship.…”

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confidence: 99%

Differential Monocytic Cell Adherence to Specific Anatomic Regions of the Canine Aorta

Margolin

Madura²,

Motte³

et al. 1995

J Vasc Res

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Circulating monocytes and vascular endothelial cells (EC) interact in a complex and dynamic manner that varies between vascular beds. The objective of this study was twofold: to ascertain if monocytic cell adhesion to vascular endothelium differed between specific anatomic regions of the canine aorta, and to investigate the effect of known EC stimulators on monocytic cell adhesion to cells from these regions. Initial in vitro studies measuring adherence of U937 cells, a human monocytic cell line, to canine jugular vein and aortic EC monolayers revealed a dose-dependent increase in adhesion to EC stimulated with interleukin-1 (IL-1), lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), or thrombin. While there was no regional difference in monocytic cell adherence to unstimulated EC in tissue culture, studies demonstrated greater monocytic cell adhesion to stimulated EC cultured from the distal versus proximal aorta. In organ culture, unstimulated adhesion of U937 cells or autologous monocytes was significantly greater to the distal aorta than the proximal aorta. Although monocytic cell adhesion to both the proximal and distal aorta increased with stimulation, the percentage increase in the proximal aorta, 1,086% with IL-1, 237% with PMA, 209% with LPS, and 174% with thrombin, was greater than in the distal aorta, demonstrating a significant functional difference in the endothelium from separate anatomic regions of a single vessel. This may have a direct relevance to the regional specificity of vascular disease.

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“…Though the hemodynamics of the pig have been shown to be similar in cardiac function to humans, variations among breeds and age of the animal need to be taken into consideration 9 . Experimental atherosclerosis has been induced by feeding minipigs an atherosclerotic diet and the induced lesions appeared to be similar to those observed in humans 10,11 . The skin of the pig is relatively hairless and tightly attached to the subcutaneous tissues like that of humans.…”

Section: General Considerationsmentioning

confidence: 66%

Use of Miniature Pig for Biomedical Research, with Reference to Toxicologic Studies

et al. 2007

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Abstract:The pigs have been a well-recognized experimental animal in biomedical research for many years. Minipigs particularly have gained in massive importance in biomedical research over the last few years. Pigs are increasingly being used as an alternative non-rodent animal species to the dog or monkey in toxicology because of the morphological and physiological similarities between porcine and human organs, especially the skin, cardiovascular system, gastrointestinal tract, and the urinary system. Accumulating data indicate that the minipig can be used for all routes of administration and is preferable to the dog or monkey in many cases. The advantages of the minipig compared to the domestic pig are its smaller size, even at full maturity, slower growth during studies, ease of handling, and controlled genotype as well as microbiologically obvious characteristics. Minipigs also have an advantage over traditional nonrodent animals because of increasing ethical concerns about the use of them in experiments. Reservoir of information from studies using minipigs is the keystone for the future diffusion of them as a good alternative to the non-rodent animals traditionally used in toxicology. (J Toxicol Pathol 2007; 20: 125-132)

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Göttingen Miniature Swine as a Model for Diet-induced Atherosclerosis

Cited by 7 publications

References 7 publications

Granulocyte Colony-Stimulating Factor Has No Adverse Effects on Atherosclerotic Lesions in High Cholesterol-Fed Miniature Swine

Granulocyte Colony-Stimulating Factor Has No Adverse Effects on Atherosclerotic Lesions in High Cholesterol-Fed Miniature Swine

Differential Monocytic Cell Adherence to Specific Anatomic Regions of the Canine Aorta

Use of Miniature Pig for Biomedical Research, with Reference to Toxicologic Studies

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