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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were carried out to compare the catabolism of intestinal lipoproteins between genetically hypercholesterolemic (RICO) and normocholesterolemic (SW) rats. Kinetics of plasma cholesteryl ester were studied after injection of cholesterol-labeled chylomicrons or VLDL. The chylomicron clearance is reduced in the RICO rat (rate constant, K = 7.2 +/- 0.1 h-1 vs. 10.7 +/- 0.1 h-1 in SW rat), while a much more minor alteration was observed in the catabolism of lymph VLDL (K = 4.3 +/- 0.6 h-1 in the RICO rat vs. 5.1 +/- 0.4 h-1). The injection of chylomicrons from SW rats to RICO rats and from RICO rats to SW rats showed that the fall in the rate of catabolism of chylomicrons in RICO rats was not secondary to an increase in the production rate, but was related to the lipoprotein particle itself without any alteration of the catabolic system. The reduction in the rate of catabolism of chylomicrons in the RICO rat could be related to a change in their apolipoprotein composition (increase in the proportion of apolipoprotein E = 12 +/- 2% vs. 3 +/- 1% in the SW rat).
Atherosclerosis 1992 Apr
PMID:Metabolism of intestinal triglyceride-rich lipoproteins in the genetically hypercholesterolemic rat (RICO) 159 Aug 25

As the intrinsic susceptibility to atherosclerosis differs among several taxonomic groups, the present studies were conducted to compare the angiotoxic responses of atherosclerosis-susceptible (quail) and -resistant (rat) animals to allylamine, a selective cardiovascular toxin. Japanese quail (125-150 g) and Sprague-Dawley rats (175-200 g) were gavaged daily for 1, 7, or 20 d with allylamine HCl (0.7, 7, and 70 mg/kg) or tap water. At the ultrastructural level, subchronic exposure of quail and rats to allylamine was associated with dose- and time-dependent disruption of the structural integrity of aortas. These alterations correlated with fluctuations in the nonprotein thiol content of avian and rodent vessels. Angiotoxicity was not associated with alterations in serum cholesterol content. At all times and doses tested, quail were more susceptible than rats to the angiotoxic effects of allylamine. Although the avian sensitivity to toxic insult was greater than that of rodents, quail aortic homogenates bioactivated allylamine to a lesser extent than rat homogenates. Collectively, these results suggest that the aortic sensitivity to toxic insult in avian and rodent species correlates with their intrinsic susceptibility to vascular injury.
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PMID:Comparative angiotoxic responses of avian and rodent species in vivo: implications in atherogenesis. 232 52

The effect of CS-514 (pravastatin; Sankyo Co., Tokyo), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, on triglyceride turnover, was studied in male Wistar rats. CS-514 (15 +/- 1 mg/day per rat) was administered as a 0.04% solution in drinking water for 14 days. Triglyceride and cholesterol in very low density lipoprotein (VLDL) and plasma triglyceride were reduced by treatment with CS-514. Plasma cholesterol level was not suppressed by CS-514. The CS-514 treated rats had a significantly suppressed triglyceride secretion rate (TgSR) during the fed state compared to control rats (0.85 +/- 0.1 vs. 1.07 +/- 0.3 mg/min, P less than 0.05). By contrast, CS-514 treatment did not suppress TgSR after an overnight fast. These data demonstrate that CS-514, an inhibitor of cholesterol biosynthesis can suppress VLDL-triglyceride secretion in rats and that this effect can be modified by dietary manipulation.
Atherosclerosis 1988 Oct
PMID:Effect of CS-514 (pravastatin) on VLDL-triglyceride kinetics in rats. 314 92

Smooth muscle cell (SMC) growth may play an important role in the pathogenesis of vascular diseases such as atherosclerosis and hypertension. Recent studies have demonstrated that, under different growth stimuli in vivo, SMC may respond by proliferation of diploid cells, polyploidization to the tetraploid (or even octaploid) state, or both. In this study, we used flow cytometry to evaluate the intrinsic tendencies of aortic SMC and nonarterial cells from rats of different strains, ages, and blood pressures to polyploidize in response to in vitro growth stimulation. Significant strain-related differences in polyploidization of aortic SMC were found (P less than 0.001): highest in WKY (normotensive inbred rat related to SHR), intermediate in SHR (genetically hypertensive rat), and lowest in Sprague-Dawley and Fischer (normotensive outbred and inbred rats). Animal age had less or no effect on the degree of polyploidization. Nonarterial cells (venous SMC and lung cells) from WKY and SHR remained essentially diploid, suggesting tissue specificity of in vitro polyploidization. Studies of the growth kinetics of uncloned and clonal populations of aortic SMC revealed decreased proliferation as the ploidy increased in WKY, SHR, and Sprague-Dawley. These findings suggest that genetic strain factors as well as cell type/site of origin significantly influence in vitro polyploidization, whereas animal age and blood pressure do not. The findings also emphasize the need to consider ploidy changes when evaluating in vitro SMC growth kinetics. Further studies will improve understanding of SMC growth regulation and the functional significance of vascular polyploidy.
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PMID:Strain and site dependence of polyploidization of cultured rat smooth muscle. 373 93

The essential part played by rheological factors in genesis of thrombosis and atherosclerosis has often been mentioned. Thus the authors have carried out a study of rheological and biochemical parameters on a genetic animal model with modifications in plasma lipids (homozygous obese "Fatty" rat) compared to the non obese heterozygous animal. The results obtained for the evolution of biochemical parameters (blood glucose, cholesterol, triglycerides) over a 16 months period confirm those published earlier. Further, a significant increase in fibrinogen level was observed in homozygous animals, and correlated with plasma viscosity. There results are also connected with changes in apparent blood viscosity which is considerably increased in homozygous rats, particularly at low shear rates (gamma less than 20 s-1). These results show the value of this animal model and the authors suggest the application of such a genetic animal model and of its heterozygous control population to both theoretical rheological and pharmacological studies on atherogenesis and hyperlipoproteinaemia.
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PMID:Hemorheological and biochemical parameters in the "fatty" rat. 709 62

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.
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PMID:Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players. 1084 50

We investigated whether endothelium-derived relaxing (EDRF) and hyperpolarizing factor (EDHF) is impaired in type 2 diabetic rats (Otsuka Long-Evans Tokushima Fatty (OLETF) rat) and whether the exercise training improves impaired EDRF and EDHF. Diabetic rats were divided into the sedentary and exercise-trained groups at the age of 16 weeks. Long-Evans Tokushima Otsuka (LETO) rats were used as age-matched non-diabetic controls. EDRF as well as EDHF induced by acetylcholine in the presence of indomethacine and L-nitro N-arginine was significantly attenuated in the diabetic rats, and was further impaired with age. Exercise training significantly improved it. Both insulin resistance and abdominal fat accumulation were significantly greater in the diabetic rats, compared with the non-diabetic rats, but were decreased in exercise-trained rats. Urinary NO(2) secretion was decrease in the diabetic rats at each age, and it was improved by exercise training. The results of the study indicated that exercise training prevented impairment of EDHF, as well as EDRF in type 2 diabetic rats, presumably due to improvement of hyperglycemia and insulin resistance and increase in the production of nitric oxide by exercise training.
Atherosclerosis 2002 May
PMID:Exercise training improves acetylcholine-induced endothelium-dependent hyperpolarization in type 2 diabetic rats, Otsuka Long-Evans Tokushima fatty rats. 1194 1

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether the lipoprotein lipase activator NO-1886 had an effect on the prevention of atherosclerosis in aged rats which undergo exercise. Exercise for 3 months did not affect plasma lipids but decreased the accumulation of visceral fat in 2-year-old rats (aged rat). Exercise also resulted in an elevation of plasma lipid peroxide (LPO) levels and impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in aged rats. On the other hand, NO-1886 decreased plasma triglycerides and increased HDL cholesterol and suppressed the elevation of plasma LPO levels caused by exercise. Furthermore, NO-1886 prevented impaired endothelium-dependent relaxation caused by exercise. In summary, the results of our study indicate that exercise may cause impaired endothelium-dependent relaxation by elevation of LPO in aged rats, and that NO-1886 prevents this impaired endothelium-dependent relaxation of aorta by reducing plasma triglycerides, elevating HDL cholesterol, and suppressing the elevation of plasma LPO caused by exercise.
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PMID:A lipoprotein lipase activator, NO-1886 prevents impaired endothelium-dependent relaxation of aorta caused by exercise in aged rats. 1208 97

Psammomys obesus (sand rat) is an appropriate model to highlight the development of hyperinsulinemia, insulin resistance, obesity, and diabetes. This animal species, with genetically predetermined diabetes, acquires non-insulin dependent diabetes mellitus when exposed to energy-rich diets. In the present study, we explored the possibility that glycation of LDL may occur in diabetes-prone P. obesus and affect platelet and macrophage functions. The glycation of LDL, isolated from diabetic animals, was significantly (P < 0.05) higher (40%) than that of control animals. The incubation of platelets with glycated LDL enhanced the reactivity of platelets by 32-44% depending on the aggregating agents (thrombin, collagen, ADP). Furthermore, LDL derived from diabetic rats were chemotactic for normal monocytes and stimulated the incorporation of [14C]oleate into cellular cholesteryl esters. The enhancement of platelet aggregation and cholesterol esterification in monocytes may contribute toward the accelerated development of atherosclerotic cardiovascular disease in diabetic P. obesus animals. This study also illustrates the relevance of studying atherosclerosis in the P. obesus animal model, as it shows an increased tendency to develop diet-induced diabetes, which is associated with cardiovascular disorders.
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PMID:Impact of in vivo glycation of LDL on platelet aggregation and monocyte chemotaxis in diabetic psammomys obesus. 1505 39

Despite the worldwide occurrence of coronary atherosclerotic heart disease (CAHD), the pathogenic mechanisms underlying this disease remain largely unknown. In this study, the experimental model of atherosclerosis in rat (CAHD rat) was established by the injection of vitamin D3 associated with high fat diet for 6 weeks. By using the proteomic approach, we comparatively analyzed the proteome of the control and CAHD rat left ventricular myocardial tissues. We reproducibly separated over 2500 polypeptides by using two-dimensional electrophoresis (2-DE) at pH range of 3-11. Among these proteins, 26 proteins with large amount were identified using micro high performance liquid chromatography mass spectrometer/mass spectrometer (micro-HPLC-MS/MS). Using PDQUEST software to process the 2-DE gel images, 38 protein spots that significantly altered in CAHD were detected. Of these, 12 proteins were identified with high confidence by using 2-DE and matrix-associated laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS). The identification of protein alterations specify to CAHD would clarify the pathogenetic mechanisms involved in the disease and might be of prognostic and therapeutic benefit.
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PMID:Comparative analysis of the proteome of left ventricular heart of arteriosclerosis in rat. 1548 91


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