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

Tissues were studied from four subjects with homozygous familial hypercholesterolemia (FH). The specimens consisted of tissues obtained from a 20-week-old fetus at autopsy, samples from a 9-year-old girl during open-heart surgery, and biopsies of cutaneous xanthomas from a 13-year-old girl and a 21-year-old man. The FH fetus, but not the 3 control fetuses, exhibited multifocal lipid deposition particularly involving the stromal cells of the thymus, spleen, and skin and both the stromal and parenchymal cells of the kidney. Only one minute focus of intimal lipid accumulation was found in the aorta and coronary arteries of the FH fetus. A segment of the ascending aorta from the 9-year-old girl showed: 1) foam-cell transformation of many medial smooth-muscle cells, 2) abnormal vascularization of the inner media and intima, and 3) intimal involvement by a typical artherosclerotic plaque with lipid deposits in thin, elongated cells that showed some myocytic features and in foam cells that lacked such features. The mitral and aortic valves of this patient also contained numerous foam cells and showed mild to moderate fibrous thickening. A segment of the saphenous vein, however, contained no lipid deposits. The three xanthomas from two FH homozygotes exhibited marked lipid accumulation in histiocytic foam cells but no lipid deposits in the endothelium of blood vessels in the lesions. The findings in this study, in conjunction with those reported in studies of other FH homozygotes, indicate that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon, and, varibly, in other extravascular sites. Since most of the intracellular lipid was in the form of non-membrane-bound neutral lipid droplets, it appears that the cytoplasm is the major site of lipid storage in this disease.
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PMID:Cellular pathology of homozygous familial hypercholesterolemia. 11 74

Arteriosclerotic and nonarteriosclerotic rats were treated with carbon tetrachloride (CCL4) to induce cirrhosis of the liver. Massive myocardial infarction was then induced in intact and CCL4-treated animals. During acute necrosis (Days 1 thru 3), animals were killed at 4, 8, 12 and 24 h on Days 1 and 2, and during myocardial repair on Days 4, 5 and 8. During the induction of cirrhosis, animals developed polydypsia, polyuria, and hyperglycemia; during myocardial infarction, the arteriosclerotic + cirrhotic animals developed severe and persistent congestive heart failure, i.e., hydrothorax. Adrenal and thymus gland weights and corticosterone levels indicated that cirrhosis per se increased pituitary--adrenal activity, particularly in arteriosclerotic animals. Enzyme levels of SGOT and SGPT demonstrated severe hepatic damage due to cirrhosis and acute myocardial infarction. Blood triglycerides and cholesterol responded abnormally in cirrhotic animals during acute myocardial ischemia due to their entrapment within hepatic cells. The cirrhotic animals manifested poor myocardial repair with persistent foci of necrosis, calcification, and a high incidence of large, occlusive, atrial thrombi. It is suggested that cirrhosis interferes with lipid metabolism and adrenal steroid conjugation leading to abnormal levels of mineralocorticoids which favor congestive heart failure, poor myocardial repair, and atrial thrombosis.
Atherosclerosis 1979 Mar
PMID:Effect of CCL4-induced cirrhosis on the pathophysiologic course of acute myocardial infarction in nonarteriosclerotic vs arteriosclerotic male rats. 46 16

Non-arteriosclerotic, virgin and arteriosclerotic breeder rats were subjected to chronic treatment with prolactin or prolactin-releasing drugs such as perphenazine and reserpine for 12 weeks. Males and females responded to the prolactin as evidenced by increased milk secretion, adrenal hyperplasia and thymus gland involution. Although the prolactin- and reserpine-treated animals gained weight and manifested pituitary gland basophilia, the perphenazine-treated animals showed considerable loss of body weight as well as involution of the pituitary gland, ovaries and testes, suggesting a condition of induced hypopituitarism. Chronic treatment with prolactin, both directly and indirectly, caused uniform increases in serum enzymes, e.g., CPK, SGOT, SGPT and LDH, lipids, e.g., triglycerides, free fatty acids and cholesterol, glucose and BUN. Corticosterone production was enhanced by prolactin, reduced by perphenazine and unaffected by reserpine. Prolactin did not induce any arterial disease in the arteriosclerosis-resistant, virgin rats but it did cause eracerbation of the usual severity of arteriosclerosis in the hilar renal arteries of the arteries sclerosis-prone, breeder rats as well as an increased incidence of "old" and "new" foci of myocardial necrosis, characteristically found in breeder rats. It is suggested that hypothalamic control of prolactin as well as ACTH release may play a role in the spontaneous arteriosclerosis which develops in repeatedly-bred, male and female rats.
Atherosclerosis
PMID:Comparative effects of prolactin, perphenazine and reserpine on non-arteriosclerotic (virgin) vs arteriosclerotic (breeder) rats. 94 17

Male and female, arteriosclerotic (breeder) and nonarteriosclerotic (virgin), Sprague-Dawley rats were made severely diabetic with alloxan. Two weeks later experimental animals had both carotid arteries ligated to induce a state of acute cerebral ischemia. After six weeks of cerebral ischemia either with or without severe diabetes the animals were killed. Animals which survived either the acute induction of diabetes or cerebral ischemia did not manifest any new episodes of cerebral ischemia. Subjects with combined diabetes and cerebral ischemia manifested the greatest loss in body weight, adrenal hypertrophy and thymus gland involution, increased levels of serum CPK and SGOT, but decreased SGPT and LDH, hyperglycemia and hypertriglyceridemia, and the most extensive cerebral edema. It is suggested that diabetic rats may have a greater predilection toward cerebrovascular accidents because the diabetic state contributes not only to an exacerbation of atherosclerosis, but also complicates any condition of cerebrovascular ischemia by creating extracerebral edema.
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PMID:Chronic diabetes followed by chronic cerebral ischemia induced by bilateral carotid artery ligation in arteriosclerotic versus nonarteriosclerotic rats. 117 43

Experiments on rabbits have shown that state of T-immunodeficiency induced by persisting virus infection promotes atherogenesis. Correction of age immunodeficiency by transplantation of the autologous bone marrow taken in young age considerably retards the atherosclerosis development. Inhibition of atherogenesis is also achieved by introduction (to animals) of natural thymic vilosene preparation which compensates a decrease in the functional activity of the thymus gland occurring under conditions of experimental hyperlipidemia.
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PMID:[Relation of atherogenesis and T-immunodeficiency]. 259 81

Oxidant injury of the vascular endothelium is considered an early event in the pathogenesis of atherosclerosis. In this study, the antioxidant effect of a 6-kDa thymic peptide (TP), isolated from calf thymus, was investigated in vitro using vascular endothelial cells. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with different concentrations of TP for 24 h, washed, and then exposed to hydrogen peroxide (H2O2) for 2 or 4 h. Cell injury was assessed by measuring cell viability with methylthiazol tetrazolium (MTT) assay, and by determining the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were monitored as malondialdehyde (MDA) with a thiobarbituric acid fluorometric assay. H2O2 (120 or 240 microM) incubated with PAEC decreased cell viability, increased LDH release, and elevated MDA production. Preincubation of PAEC with TP (25-150 micrograms/ml) before H2O2 exposure significantly increased cell viability, decreased LDH release, and reduced MDA production. These results demonstrate that TP can protect vascular endothelial cells from oxidant injury. The data thus suggest that TP may be useful for the prevention and/or treatment of atherosclerosis, and further suggest that immune modulating agents may directly or indirectly influence the functions of vascular endothelium.
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PMID:Thymic peptide protects vascular endothelial cells from hydrogen peroxide-induced oxidant injury. 849 41

The thymus hormones were reported to be effective on lipid peroxidation and the antioxidant system. Thymus plays a broader role than just regulating the immune system. Thymosin alpha 1 is the first subgroup extracted from thymosin F5 and has higher biological activity than thymosin F5. In the present study, we have examined the effects of thymosin alpha 1 on lipid levels and lipid peroxidation and glutathione (GSH) content in the plasma, liver and aorta tissues of atherosclerotic rabbits. At the end of thymosin alpha 1 treatment, we determined the lipid levels and lipid peroxidation of the plasma, liver and aorta tissues and hepatic subcellular fractions in these rabbits. Our results demonstrated that thymosin alpha 1 might normalize changed lipid levels and increased lipid peroxides and also elevate decreased GSH in the plasma, liver and aorta tissues of atherosclerotic rabbits. Results of this study suggest that thymosin alpha 1 may be beneficial to prevent and/or to treat atherosclerosis.
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PMID:Thymosin alpha 1 protects liver and aorta from oxidative damage in atherosclerotic rabbits. 880 25

The function of the immune system declines with age. It is the aim of the present review to demonstrate that it makes sense to distinguish between primary and secondary alterations of immune reactivity in the elderly. Primary changes occur as the result of an age-dependent intrinsic decline of immune responsiveness. They also occur in healthy persons, i.e. persons selected according to the criteria of the SENIEUR protocol of the European Community's Concerted Action Program on Aging (EURAGE). T lymphocytes are hereby more severely affected than B cells or antigen presenting cells, possibly due to the involution of the thymus, which is almost complete at the age of 60. Secondary immunological changes occur as the result of environmental factors including diet, drug intake, physical activity etc. or are alternatively due to underlying diseases. In this article, the effects of high lipid intake as well as the impact of diseases, such as for instance Alzheimer's disease and atherosclerosis, will be addressed. The results underline the complexity of immunological alterations to be expected in old age. Changes in the aging immune system represent an opportunity for increased frequency and severity of disease and endanger the protective effect of vaccination.
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PMID:Primary and secondary alterations of immune reactivity in the elderly: impact of dietary factors and disease. 947 75

CD40-CD154-mediated contact-dependent signals between B and T cells are required for the generation of thymus dependent (TD) humoral immune responses. CD40-CD154 interactions are however also important in many other cell systems. CD40 is expressed by a large variety of cell types other than B cells, and these include dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells, fibroblasts, and endothelial cells. CD40- and CD154-knockout mice and antibodies to CD40 and CD154 have helped to elucidate the role of the CD40-CD154 system in immune responses. Recently published studies indicate that CD40-CD154 interactions can influence T cell priming and T cell-mediated effector functions; they can also upregulate costimulatory molecules and activate macrophages, NK cells, and endothelia as well as participate in organ-specific autoimmune disease, graft rejection, and even atherosclerosis. This review focuses on the role of the CD40-CD154 system in the regulation of many newly discovered functions important in inflammation and cell-mediated immunity.
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PMID:CD40 and CD154 in cell-mediated immunity. 959 26

Many factors play important roles in the development of atherosclerotic lesions. The leading risk factor for atherosclerosis is familial hypercholesterolaemia (FH). FH is a genetic disease characterized by a deficiency of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells, a high level of serum LDL, and early development of atherosclerosis and skin xanthoma. Watanabe and colleagues have developed a line of rabbits with unprovoked hypercholesterolaemia, increased blood level of LDL, pronounced atherosclerosis and skin xanthoma. These Watanabe Heritable Hyperlipidaemic (WHHL) rabbits possess an inheritable mutation of one gene, similar to that in human FH. The morphogenesis of atherosclerosis in patients with FH is characterized by multifocal deposit of lipids in the stromal cells of thymus, spleen, skin, interstitial and parenchymatous cells of kidneys and the presence of some single foam cells in aorta. The manifestation of atherosclerotic lesions in WHHL rabbits increases progressively with age but the presence of atherosclerotic lesions in newborn WHHL rabbits suggest that the process may commence in utero. Moreover, the main mass of plasma cholesterol in WHHL rabbits is first found in LDL and to a lesser degree in lipoproteins of intermediate density. This is contrary to diet-induced atherosclerosis in rabbits where the main mass of serum cholesterol is found in very low density beta-lipoproteins. Thus the distribution of cholesterol among lipoprotein fractions differs from that in WHHL rabbits. Atherosclerotic damage of arteries in WHHL rabbits goes through several stages. During the progression of intimal damage, lipid and foam cell deposits are found in the internal surface together with developing plaques and increased content of lipids in the tunica media. Calcification often follows this process. The main factors initiating atherosclerosis in WHHL rabbits are adhesion of leukocytes and platelets to endothelial cells and the accumulation of lipids in the aortic wall. The deposits of lipids in macrophages and intimal smooth muscle cells in WHHL rabbits occurs mostly at the expense of cytoplasmic neutral lipid particles with some accumulation in lysosomes. Hypertension as a risk factor increases the area of atherosclerotic damage in all arterial vessels in WHHL rabbits, particularly in the thoracic and abdominal aorta. Morphogenesis of the development of atherosclerosis in WHHL and diet-induced atherosclerosis in rabbits was similar, but differs from rats with heritable hypercholesterolaemia. Damage or loss of endothelial cells can predispose the atherosclerotic vessels to vasospasm and can leave vessels unprotected against vasoconstrictor stimuli. The development of the WHHL model has not only given insight into the mechanisms of development of familial hypercholesterolaemia but has also provided a model for assessing various therapeutic approaches for the prevention and treatment of atherosclerosis.
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PMID:Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis. 969 Jan 37


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