Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls.
Atherosclerosis 1976 Sep
PMID:Increased collagen synthesis and the kinetic characteristics of prolyl hydroxylase in tissues of rabbits with experimental arteriosclerosis. 18

(1)Using both an explant system from swine thoracic aorta and an aortic smooth muscle cell culture system, we have investigated the effect of lipoproteins on the synthesis of DNA in the absence of serum or serum derivatives. (2)Chemical and morphological data from both systems confirm that (a) neither VLDL, LDL nor HDL account for any appreciable part of the DNA synthesis activity of whole serum. (b) There is no difference in activity between lipoprotein fractions derived from either normocholesterolemic or hypercholesterolemic serum. (c) The activity resident in whole serum is present largely in the pelleted serum protein fractions and in the soluble resideu. (3) The data suggest that smooth muscle cell proliferation results from the interaction of lipoproteins with other factor(s) in serum.
Atherosclerosis 1977 Jun
PMID:Effect of lipoprotein on in vitro synthesis of DNA in aortic tissue. 19 76

Effects of hyperlipidemic, normolipidemic and high-density-lipoproteinemic (HD lipoproteinemic) sera from active runners were studied on cultured human aortic smooth muscle cells. The synthesis of DNA, hyaluronic acid and sulphated glycosaminoglycans (GAGs) in the presence of the various sera was measured by the incorporation of [3H]-thymidine and [3H]-glucosamine. The HD lipoproteinemic sera from runners stimulated the synthesis of DNA and sulphated GAGs less than normolipidemic and hyperlipidemic sera. The hyperlipidemic sera stimulated the synthesis of DNA slightly more than the other sera, but only after a 24 h preincubation. Accordingly, the concentration of HDL-cholesterol in serum was negatively correlated with the synthesis of DNA (r = -0.77, P less than 0.01) and sulphated glycosaminoglycans (r = -0.81, P less than 0.01). The sulphated GAGs/hyaluronate ratio was smaller in the presence of HD lipoproteinemic serum as compared with the other sera. The proliferation of aortic smooth muscle cells and the rate at which they synthesize sulphated GAGs have been considered important during the initiation of atherosclerosis in vivo. The present results suggest that sera having differences in the relative amounts of various lipoprotein fractions differ significantly in their influence on both of these arterial smooth muscle cell functions in vitro.
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PMID:Effect of sera from hyperlipidemic subjects and high-density lipoproteinemic runners on the synthesis of DNA and glycosaminoglycans by cultured human aortic smooth muscle cells. 22 58

Human aortic medial smooth muscle cells (SMC) and umbilical vein endothelial cells (EC) in culture were exposed to various concentrations of plasma low density (LDL) and high density (HDL) lipoproteins prepared from normolipemic donors in order to assess their effects on cell growth. So that the effects of each lipoprotein could be evaluated separately and in combination, lipoproteins were added to culture medium containing lipoprotein deficient serum (LPDS, d greater than 1.25 g/ml at a protein concentration of 4.5 mg/ml of medium). The addition of LDL at cholesterol concentrations of 160 microgram/ml of culture medium, resulted in significant reductions in both the number of SMC and EC cells per dish within 3 days of exposure (P less than 0.001, SMC; P less than 0.01, EC), when compared with LPDS controls and the starting cell numbers. This cytotoxic phenomenon was dose-related, and only at LDL cholesterol concentrations equal to or below 50 microgram/ml were no marked changes observed. In contrast, HDL at all concentrations tested produced no such deleterious effects. Autoradiographic assessment of DNA synthesis confirmed these findings. After 48 h of continuous exposure to tritiated thymidine, labeling indexes reached much lower plateaus in the LDL-treated groups.
Atherosclerosis 1979 Mar
PMID:LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture. 22 85

The activity of phosphofructokinase (PFK, 2.7.1.11) was measured in arteries of very young (5-8 week old) pigeons known to differ in susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly higher in the atherosclerosis-susceptible White Carneau (WC) pigeons than in the resistant Show Racers (SR). The difference was significant whether enzyme activity was calculated on the basis of extract protein, DNA content or fat-free dry weight. In the White Carneau arteries the activity of the enzyme was higher in the female than the male pigeons. PFK is a key regulatory enzyme of glycolysis and is subject to fine control adjustments. A low ATP/ADP ratio and a fall in citrate concentration, as for example, induced by hypoxia, are meditors of a feedback mechanism leading to a rise in PFK activity and enhancement of glycolysis for energy production. This mechanism appears to be the cause of the higher PFK activity in the WC arteries, because related studies indicate impaired Krebs cycle activity in these vessels. It is suggested that the increased dependence of the WC arteries on glycolysis facilitates the development of atherosclerosis in this pigeon strain and that the mechanism is similar to the mechanism by which tissue hypoxia causes lipid accumulation and connective tissue alterations in the arterial wall.
Atherosclerosis
PMID:Elevation of arterial phosphorfuctokinase activity associated with susceptibility to atherosclerosis in pigeons. 23 61

An integrative theory is proposed in which environmental carcinogenesis is viewed as a process by which the genetic control of cell division and differentiation is altered by carcinogens. In this theory, carcinogens include physical, chemical, and viral "mutagens," as well as chemical and viral gene modulators. Existing explanations of carcinogenesis can be considered either as somatic mutation theories or as epigenetic theories. Evidence seems to support the hypothesis that both mutations and epigenetic processes are components of carcinogenesis. The mutational basis of cancer is supported by the clonal nature of tumors, the mutagenicity of most carcinogens, high mutation frequencies in cells of cancer-prone human fibroblasts lacking DNA repair enzymes, the correlation of in vitro DNA damage and in vitro mutation and transformation frequencies with in vivo tumorigenesis, age-related incidences of various hereditary tumors, and the correlation between photoreactivation of DNA damage and the biological amelioration of UV-induced neoplasms. Since both mutagens and gene modulators can be carcinogenic it may be that carcinogens affect genes which control cell division. An integration of the mutation and epigenetic theories of cancer with the "two-stage" theory and Comings's general theory of carcinogenesis is proposed. This integrative theory postulates that carcinogens can affect regulatory genes which control a series of "transforming genes." A general hypothesis is advanced that involves a common mechanism of somatic mutagenesis via error-prone repair of DNA damage which links carcinogenesis, teratogenesis, atherosclerosis and aging. Various concepts are presented to provide a framework for evaluating the scientific, medical, and social implications of cancer.
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PMID:Environmental carcinogenesis: an integrative model. 36 70

The pathogenesis of atherosclerosis is hypothesized to occur as a response to various forms of injury to the lining arterial endothelial cells. The resulting endothelial alterations could potentially lead to interactions between platelets in the circulation and the underlying subendothelial connective tissue or with the altered endothelial cells themselves. Such interactions provide an opportunity for platelet degranulation and release of a platelet-derived growth factor. This factor has been shown in cell culture to be an extremely potent mitogen and will induce DNA synthesis and cell multiplication of a number of cells including smooth muscle cells, fibroblasts, and other mesenchymally derived cells. Chronic endothelial injury and repeated interactions between platelet-derived mitogens, plasma components, and the underlying arterial smooth muslce cells would promote the progression of the intimal proliferative lesions of atherosclerosis that lead to the clinical sequelae associated with this disease process.
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PMID:The pathogenesis of atherosclerosis. 37 62

Arterial tissue was obtained from twelve severely obese patients during jejuno-ileal by-pass surgery. The arterial DNA content was inversely correlated with the sum of venous glucose values during an oral glucose tolerance test (rs = -0.72). This observation may have implications on the known relationship between decreased glucose tolerance and early manifestations of atherosclerosis.
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PMID:Cholesterol and DNA content in arterial tissue in severe obesity: their relation to some risk factors for ischaemic heart disease. 41 81

With suitable radioactively labelled precursors the mitotic (using 3H-thymidine) and the productive metabolisms (using 3H-proline and 35S-sulphate) were investigated on various kinds of joint- etc. cartilage from mice with genetically caused arthrosis. The autoradiographic analyses were performed using 3H-thymidine-, 3H-proline- and 35S-sulphate-indices and the statistical evaluation of the findings led to the following results: the synthesis level of sulphated glycosaminoglycans (GAG) in the cartilage ground substance is lower for 5--6 month-old mice than for the 16--17 month-old animals of this genetic arthrosis strain. This is most distinct in the 3rd (= basal) zone of the knee-joint cartilage which increased to double the comparable value in this period. In all 3 zones of the knee-joint cartilage GAG-synthesis is considerably greater than the collagen synthesis according to these autoradiographic analyses. These findings can be detected before any histologically or histochemically demonstrable cartilage alterations and represent therefore the earliest signs of a so-called "pre-arthrosis". Collagen synthesis decreases thereby, and the same holds for DNA-synthesis and the mitotic metabolism of the cartilage cells - according to the findings to date. However the question is still under investigation whether arthrosis (like atherosclerosis) also starts with an increase in cell-turnover. This question is not only of theoretical interest, it has practical clinical consequences, even for the treatment. These investigations also serve this clinically relevant question because arthrosis is the most common human joint disease.
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PMID:[Autoradiographic studies on the mitotic and productive metabolism of the articular cartilage in mouse genetic arthritis]. 47 31

Many of the morphologic and biochemical features of porcine coronary atherosclerosis produced by high cholesterol, high fat diet and propoylthiouracil returned to control values after cessation of the atherogenic regimen. These include disappearance of foam cells and a decrease in lipid content, DNA concentration, and DNA and protein synthesis. The morpholigic and biochemical features of te atherosclerotic lesions described herein were similar to those produced in swine and other species by a variety of inciting agents during both the progression and regression phase of the disease. These results indicate that the porcine propylthiouracil-diet model may be useful for the study of coronary lesions. Second, the similarities of response of arterial tissue in several experimental animals suggest the possibility that human coronary lesions by analogy may regress under therapeutic regimens.
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PMID:Morphological and biochemical changes in propylthiouracil-diet induced coronary atherosclerosis under a regression regimen. 55 77


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