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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of fish oil on accelerated graft coronary arteriosclerosis was assessed in Lewis to Brown-Norway rat heterotopic cardiac allografts. Twelve Brown-Norway rats were supplemented with 2 ml/kg/day of fish oil (68.3 mg eicosopentaenoic acid and 47.5 mg decosahexaenoic acid per milliliter). Eleven additional animals, receiving an isocaloric amount of safflower oil, served as control. All diets began 1 week before operation. Immunosuppression was obtained with low-dose cyclosporine (2 mg/kg/d). When killed (100 days), there were no significant differences in percentage weight gain, graft function, or histologic rejection score. Although lipid profiles were comparable, total cholesterol:high-density lipoprotein ratio was marginally higher in animals treated with fish oil (p = 0.069). Mean percentage luminal occlusion (before and after correcting for differences in size between coronary vessels analyzed) and average intimal thickness were similar between animals treated with fish oil and safflower oil as assessed by computer-assisted digitized, morphometric planimetry. In all allografts, donor interstitial dendritic cells were repopulated with recipient dendritic cells. The major histocompatibility complex class II cell density in the fish oil group did not differ significantly from rats supplemented with safflower oil (1.48 +/- 0.68 vs 1.48 +/- 0.65 cells per mm2, p = 0.995). In conclusion, fish oil did not exert any beneficial effect over safflower oil in terms of graft coronary arteriosclerosis, histologic rejection, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of fish oil on graft arteriosclerosis and MHC class II antigen expression in rat heterotopic cardiac allografts. 175 47

Rupture of the internal elastic lamina may occur spontaneously with age in certain arteries of the rat and to various extents in different strains. This phenomenon may have some bearing on certain aspects of arterial pathology. For this study, we investigated biochemically the mechanisms of formation of interruptions in the internal elastic lamina (IIEL) by comparing aortas of Brown Norway (BN) rats, which develop numerous IIEL in the abdominal aorta, with those of Long-Evans (LE) rats, which develop none. We isolated aortic elastin from BN and LE rats and determined its amino acid composition and its susceptibility to different elastases. No differences were found between the two strains, but the quantity of elastin isolated per aorta was lower in the BN than in the LE rats. Elastase-like activity (ELA) of whole aortic extracts, measured with Suc(Ala)3NA as a substrate, was greater in the BN rats than in the LE rats of both sexes. The assay of ELA in endothelium, media, and adventitia extracted separately showed very low levels in the media compared to the endothelium and adventitia. The endothelium accounts for about one-half of the total aortic ELA, but a difference between the two strains was detected only in the adventitia. With 3H-insoluble elastins prepared from BN and LE aortas as substrates, elastinolytic activity (EA) was detected only in extracts of endothelium after prior exposure to trypsin. Extracts from BN endothelium on BN elastin were more active than were those from LE endothelium on LE elastin. The assay of lysyl oxidase activity in aortic extracts from the two strains with 3H-collagen from chick embryo calvaria as the substrate showed a lower activity in the BN than in the LE rats. Taken together, these results suggest that increased elastase activity and decreased lysyl oxidase activity may be involved in the formation of IIEL.
Arteriosclerosis
PMID:Role of elastase and lysyl oxidase activity in spontaneous rupture of internal elastic lamina in rats. 197 75

Accelerated coronary arteriosclerosis remains the most important factor limiting long-term survival of heart transplant recipients, and dietary fish oil supplementation with omega-3 polyunsaturated fatty acids has been suggested to have a protective effect against coronary disease in epidemiologic studies and to inhibit arteriosclerosis in animal experiments. Therefore we tested the hypothesis that fish oil administration inhibits the development of allograft coronary arteriosclerosis by using a heterotopic heart transplant model. Three groups of Lewis rats (n = 10 each) received heterotopic heart transplants from Brown-Norway donors and were treated with cyclosporine intraperitoneally on a tapering schedule. Group 1 received fish oil daily by gavage (2 ml/kg/day; Emulsified Super MaxEpa, Twin Labs, Ronkonkona, N.Y.). Group 2 received an equal amount of safflower oil, as well as aspirin (1 mg/kg/day) and dipyridamole (3 mg/kg/day). Group 3 received safflower oil only. All rats were put to death 110 days later, at which time there was no statistically significant difference in graft function as assessed by palpation (scale 0 to 4, mean = 3.7 +/- 0.5 [+/- standard deviation]; analysis of variance: p = 0.72) or in microscopic grade of rejection (scale, 0 = none to 3 = severe, mean 2.1 +/- 0.6; analysis of variance: p = 0.68) between any of the groups. The coronary arteries were histologically scored for the degree of arteriosclerosis (scale, 0 = normal to 3 = occluded), and a mean grade of coronary disease was calculated for each heart. The fish oil-treated group had significantly less severe allograft coronary arteriosclerosis (analysis of variance: p = 0.005) than did groups 2 and 3 (mean grade 0.23 +/- 0.22 versus 1.04 +/- 0.75 and 0.96 +/- 0.55 (p less than 0.05, Scheffe F test), whereas groups 2 and 3 had similar degrees of coronary disease (p = no significant difference). These data demonstrate that fish oil supplementation inhibited accelerated coronary arteriosclerosis in this cyclosporine-treated heart allograft rat model, whereas antiplatelet agents in these doses were ineffective. Although the mechanism of this protective effect remains incompletely understood, it does not appear to involve enhanced immunosuppression. Fish oil and specific omega-3 polyunsaturated fatty acids should be further investigated as potentially useful agents to ameliorate accelerated allograft coronary arteriosclerosis in other animal species and perhaps eventually in man.
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PMID:Inhibition of accelerated cardiac allograft arteriosclerosis by fish oil. 265 23

We demonstrate here, for the first time, the mitogenic effect of insulin-like growth factor-I (IGF-I) on the development of transplant arteriosclerosis in a rat orthotopic aorta allotransplantation model (Brown Norway to Lewis). 125I-IGF-I uptake by the abdominal aorta of male Brown Norway rats occurred within 30 min. Consequently, we exposed the donor abdominal aorta to 0, 200, or 500 ng/ml IGF-I at 37 degrees C for 30 min ex vivo (n=7 per group), before transplantation. Fourteen days after transplantation, intimal thickening of the allografts in each of the three groups was 0.18+/-0.02 (IGF-I at 0 ng/ml), 0.23+/-0.03 (IGF-I at 200 ng/ml), and 0.30+/-0.03 (IGF-I at 500 ng/ml), respectively (mean+/-SEM, P<0.005 for 500 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation (cpm/microg protein) in the transplanted grafts at 7 days after transplantation (n=4 per group) was 40.6+/-7.6, 78.5+/-12.3, and 66.9+/-10.1, respectively (P<0.01 for 200 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation in the native thoracic aorta of the recipient was 23.4+/-4.4. We conclude that acceleration of allograft myointimal proliferation and intimal thickening was induced directly by IGF-I.
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PMID:Acceleration of arteriosclerosis of the rat aorta allograft by insulin growth factor-I. 911 42

In this study, phenotypic expression of spontaneous elastic laminae defects within the rat abdominal aorta was examined. Lesions in Brown Norway (BN) rats were compared with those of New Zealand genetically hypertensive (GH) rats. BN and GH rats were cross-bred to determine the phenotypic expression of these lesions in successive F(1) and F(2) generations. Lesions were assessed by distribution, number and a semiquantitative index of severity. All BN aortae contained numerous elastic tissue defects. In comparison, GH aortae contained only occasional elastic tissue lesions. F(1) aortae contained lesions in numbers similar to those of the parental BN strain; however, F(1) lesions were of significantly greater severity. Within the F(2) generation, a wide range in both lesion numbers and severity indices was observed, with approximately a quarter of animals having lesion numbers analogous to the GH parental strain. In conclusion, this study indicates that the spontaneous elastic tissue lesions observed within BN rats are consistent with an autosomal dominant, possibly single gene, effect. Moreover, epistatic effects, derived from the GH strain, may influence the severity of these lesions. The gene(s) responsible may be important in the development of conditions such as arteriosclerosis and aneurysms in humans.
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PMID:Spontaneous elastic tissue lesions in the rat abdominal aorta, a genetically determined phenotype. 1075 92

We examined the effect of allogeneic and xenogeneic immune responses on the histopathological changes in aortic valve grafts and the influence of preservation techniques on these changes. Brown Norway rats and Syrian hamsters were used as allogeneic and concordant xenogeneic donors of aortic valve grafts, respectively. The allografts and xenografts were implanted heterotopically in the abdominal aorta of Lewis rat recipients immediately after harvest (homovital), after cryopreservation, or after preservation with antibiotics at 4 degrees C (fresh preservation). Allografts and xenografts were explanted at days 7, 28 or 56 and at days 3, 7 or 14, respectively, for the histopathological examination. The allografts underwent histological changes characteristic of graft arteriosclerosis. No significant effect of cryopreservation on these changes was observed. The fresh-preserved graft was, however, predisposed to focal destruction of the elastic fibers and to early disappearance of the leaflet. The lesions in xenografts were characterized by severe destruction of the elastic fibers. Compared to homovital xenografts, both cryopreserved and fresh-preserved xenografts showed more prominent disruption of the elastic fibers, well-developed valvular and vascular thrombi and earlier disappearance of the leaflet. In conclusion, it could be assumed that failure in retention of cellular and extracellular components during fresh preservation accelerates structural deterioration of allografts. As for xenografts, even the extracellular matrix may have potential xenogeneic immunogenicity. There is a possibility of these preservation techniques reducing xenogeneic immunogenicity of the endothelial cells, probably because of loss of these cells. However, it appears that, even in this setting, other cellular and extracellular components could trigger immune responses causing structural deterioration of xenografts.
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PMID:The effect of allogeneic or xenogeneic immune responses and preservation techniques on transplanted aortic valve grafts. 1081 85

Allograft arteriosclerosis is an important characteristic of chronic graft rejection. In allograft arteriosclerosis there is a striking loss of medial smooth muscle cells (SMCs) before the development of a concentric intimal proliferative response. In this study we evaluated the role of CD8+ T lymphocytes in this medial SMC loss. Brown Norway aortic segments were transplanted into Lewis animals for 60 days (long allo-exposure) or 20 days (short allo-exposure). After 20 days allogeneic exposure aortic segments were transplanted back into syngeneic (Brown Norway) animals for 40 days. Experimental animals were treated with mAb to CD8. Apoptosis was measured by terminal dUTP nick-end labeling at 20 days and morphometry analyzed at 60 days to evaluate medial and intimal changes. Anti-CD8 treatment significantly lowered CD8+ T cell counts in peripheral blood, reduced medial SMC apoptosis at 20 days, and increased medial SMC counts at 60 days. Both short- and long-allogeneic exposure groups confirmed these findings and demonstrated that medial SMC loss is proportional to the length of allogeneic exposure. Antibody depletion of CD8+ T cells results in reduced medial SMC apoptosis and better medial SMC preservation. This supports the hypothesis that medial SMC loss occurs by apoptotic death and is driven by CD8+ T lymphocytes.
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PMID:CD8+ T lymphocytes mediate destruction of the vascular media in a model of chronic rejection. 1098 Jan 25

Considering the morphological findings in egyptian mummies at the beginning of the 20th century, atherosclerotic lesions were also apparent in pharaoh mummies more than 3500 years ago. Hippokrates (469-377 b.c.) described the sudden (cardiac) death, whereas Erasistratos had documented the typical claudication intermittens symptoms of peripheral arterial disease approximately 300 b.c. Later on in 1575, Fallopius observed severe pathological findings in arteries which he has characterized as a 'degeneration to bones', suggesting the presence of calcified atherosclerotic lesions. The relation between coronary lesions and the symptoms of angina pectoris was postulated in 1799 by Parry, however, only more than 80 years later angina pectoris was interpreted as a result of myocardial ischemia by Potain. During that time, the term 'arteriosclerosis' was firstly created by Lobstein in his 'Lehrbuch der pathologischen Anatomie', published in 1835. With the beginning of the last century, the pathophysiological aspects of plaque development were investigated in more detail by a number of researchers. In this context, people such as Saltykow, Chalatow and Anitschkow are important to notice. In 1914, Anitschkow firstly described the role of cholesterol accumulation in the vessel wall for the development of atherosclerosis. He used a cholesterol-fed rabbit model, which is the most important model of experimental atherosclerosis up to now. He also firstly described the 'Cholesterinesterphagozyten', which today commonly are known as foam cells, derived from macrophages. Using the cholesterol-fed rabbit model as well, already in 1942, Ludden et al. could demonstrate the atheroprotective effect of estrogen experimentally, a finding, which got later confirmed in the primate model and epidemiological studies. In the last three decades our knowledge has expanded by a large number of findings, based on morphological, immunohistological and molecular methods. In this context, one major contribution was the discovery of the LDL-receptor and its importance for the development of atherosclerosis by Brown and Goldstein, and the setting up of the 'response to injury hypothesis' by Ross and Glomset. At the present, we understand atherosclerosis as a complex (and at least in part as a physiological) phenomenon, beginning in the early childhood. The pathological aspect, making it to a disease, is depending on individual growth dynamics and plaque localization. The following key processes during the development of atherosclerosis are identified: 1) Endothelial injury, 2) intimal cholesterol accumulation and monocyte invasion with subsequent foam cell formation, 3) migration and proliferation of smooth muscle cells with expression of extracellular matrix 4) local thrombus formation with secondary organization 5) calcification and/or plaque rupture 6) final occlusion due to plaque rupture/thrombus formation. The classical concept of cardiovascular risk factors does only partially explain the origin of atherosclerosis. For the future, further mechanism(s) need to be identified and studied (genomic pathways, hormonal aspects, infective components, etc.) probably opening an effective therapeutical strategy to prevent and treat atherosclerotic diseases.
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PMID:The discovery of the pathophysiological aspects of atherosclerosis--a review. 1168 58

Chronic rejection is the leading cause of late graft loss following solid organ transplantation and is characterized by a vasculopathy referred to as allograft arteriosclerosis. While the etiology of allograft arteriosclerosis remains unknown, it has been hypothesized that migration of donor medial smooth muscle cells into the intimal compartment is responsible for the formation of the occlusive lesion (neointima). In this study we have used aortic interposition grafts between fully histoincompatible rat strains (Brown Norway and Lewis) to investigate the origin of the neointimal cells. Three transplant paradigms were used: BN to Lew, Lew to BN and BN to Lew with immunosuppression. Neointimal cells were isolated from aortic transplant tissue through an EDTA wash/mechanical stripping technique. We have developed polymerase chain reaction primers to the MHC1 allele that are specific to each rat strains' DNA. Polymerase chain reaction analysis, using the strain-specific primers and purified neointimal cell DNA from transplanted aortic tissue from all three experimental groups, demonstrated that the neointimal cells are of recipient, and not donor origin.
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PMID:Recipient cells form the intimal proliferative lesion in the rat aortic model of allograft arteriosclerosis. 1209 80

The inhibitory effect of astilbin on transplant arteriosclerosis in murine model of thoracic aorta transplantation was examined. Model of rat thoracic aorta transplantation was established. Ninety rats were divided into three groups. In isograft group, the thoracic aorta of Brown Norway (BN) rat was anastomosed with the abdominal aorta of another BN rat. In allograft group, the thoracic aorta of BN rat was anastomosed with the abdominal aorta of Lewis rat. In astilbin group, the rats receiving allo-transplantation were given astilbin 5 mg/kg per day for a time of 28 days. The donor thoracic aorta and the recipient abdominal aorta were anastomosed by means of a polyethylene cannula (inner diameter: 1.5 mm, length: 3 mm length). The grafts were histologically examined for structural changes. The areas of arterial lumen and endatrium were calculated. Our results showed that, in the allograft group, 28 days after allografting, conspicuous proliferation of smooth muscles and infiltration with a great number of inflammatory cells were found in the tunica intima and tunica media. Astilbin significantly inhibited the proliferation of smooth muscles and ameliorated the infiltration of inflammatory cells thereby prevent against the development of transplant arteriosclerosis. It is concluded that asltilbin can effectively prevent the development of arteriosclerosis in allotransplant by inhibiting the proliferation of smooth muscles and inhibit the proliferation of smooth muscles in tunica of intima and media and reducing infiltration of the inflammatory cells.
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PMID:The inhibitory effect of astilbin on the arteriosclerosis of murine thoracic aorta transplant. 1939 7


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