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)

Elastins from normal appearing areas of human thoracic aortae with varying degrees of mineralization were taken from subjects of different ages and purified by autoclaving their amino acid compositon, Ca and P contents and N terminal profiles were determined before and after EDTA decalcification. (1) Decrease in desmosine concentration with increasing age was accounted for by dilution of the elastin by autoclave-resistant polar glycoproteins. (2) The appearance and growth of a mineral phase with a Ca/P molar ratio typical of apatites was accompanied by an increased association of polar contaminants with elastin. (3) After 24 h EDTA treatment, small and constant amounts of Ca were still apparent although P was absent, in elastins from all age groups. (4) The undialyzable fraction of the material solubilised by EDTA consisted mainly of elastin fragments, glycoproteins and Ca. (5) All the elastin samples showed the same type of N-terminal amino acids. In low and medium mineralized samples the concentration of amino end-groups was slightly increased, while in highly mineralized elastin the content of N-terminal residues was three times greater than in normal young elastin. Extraction with EDTA reduced the amount of end-groups to a normal level. It is suggested that in the initial stages of elastin fibre mineralization, an increased amount of autoclave-resistant glycoproteins becomes associated with elastin; and that with ageing, degradative changes involving peptide-bond cleavage may occur. However, evidence of degradation is found only in old and highly mineralized elastin samples.
Atherosclerosis
PMID:Age-related chemical changes in human elastins from non-atherosclerotic areas of thoracic aorta. 94 22

Fibrous proteins were measured in five arterial beds in adult cynomolgus monkeys after administration of atherogenic and regression regimens. Atherosclerosis was induced by feeding the monkeys a hypercholesterolemic diet containing 1.2% cholesterol for 17 months. A low-fat, cholesterol-free regression diet was then given for 60 days, 200 days, and 20 months. In atherosclerosis, collagen concentration (mg/g dry weight) and collagen content (mg/cm length of artery) both increased. At 200 days of regression the collagen concentration, but not the collagen content, was higher than it was in atherosclerosis. In late regression (20 months), the collagen content was lower than it was in atherosclerosis, although in the five arterial beds considered together the collagen concentration was not significantly lower. Both the elastin concentration and the elastin content rose in atherosclerosis and decreased in regression. These mass data suggest that fibrous proteins are lost from the arterial wall during a regression regimen. Correlative evidence suggests that younger intimal fibers may be chiefly susceptible to fibrolytic activity, leaving dense intimal scars characteristic of regressed arteries.
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PMID:Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets. 111 35

Elasticity and elastin of arteries in 106 dead people aged 14--74 years were investigated using physico-chemical methods. Depending on the character of morphological manifestations, aortas and arteries were divided into following groups: 1) without morphological manifestations of atherosclerosis; 2) affected by atherosclerosis; 3) vessels of patients who had suffered from atherosclerosis and hypertensive disease; 4) aortas and arteries of patients with atherosclerosis in combination with other somatic diseases. In atherosclerosis and hypertensive disease there were observed specific shifts in the character and intensity of fluorescence of elastin and elasticity as a whole. The intensity of primary fluorescence as an atherosclerotic process progressed and in concomitant hypertensive disease gradually changed. In atherosclerosis there were noted changes in transversal bands in elastin. The growth of transversal bands and intensity of fluorescence were found to be interrelated. Optical density of dissolved elastin with wave lengths (lambda) 240, 260, 280, 300, 320, 360, 400, 490 nm and pH 7.7 and 8.6 was studied. The peak of intensity of absorption of the solution of elastin in all groups referred to above was noted at the wave length lambda=240 nm. Amino-acid composition of dissolved elastin was also studied. It was established that as the process of atherosclerosis progressed, the content of lysine in the wall increased depending on the phase of the process -- lipoidosis, atheromatosis, etc. In the vascular wall there were observed changes in monoamino-oxidase, the latter being of particular importance for maintaining the level of cuprum in tissues.
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PMID:[Arterial elastin in atherosclerosis and hypertensive disease]. 118 Jun 99

(1) Annulus fibrosus and nucleus pulposus of human intervertebral discs at different degrees of atherosclerosis were disintegrated by elastase. (2) The material disintegrated by elastase -- called elastolysate -- could be separated into hydrophobic (apolar) and hydrophilic (polar) peptides. Parallel with the degree of atherosclerosis the amount of hydrophobic peptides increased, whereas that of the hydrophilic peptides decreased. (3) In annulus fibrosus and nucleus pulposus two kinds of fluorescence maxima were measured. The one, A:F 350:405, is known as fluorescence maxima of elastin- and collagen-peptides. The other, A:F 410:470, is related to a similar substance called atherofluorescent component (AFC), which has been isolated before from the plaques of atherosclerotic aorta. This substance accumulates mainly in nucleus pulposus and resembles lipofuscin-like bodies. (4) These bodies show a positive reaction with thiobarbituric acid, giving a red coloration characteristic for malondialdehyde. In nucleus pulposus the amount of lipofuscin-like substances is much greater than in annulus fibrosus. (5) The hydrophilic peptides, although they show the same fluorescence maxima as the hydrophobic peptides, do not give any reaction with thiobarbituric acid. It is supposed that in these cases the cross-linked protein contains instead of malondialdehyde other reactive aldehydes.
Atherosclerosis
PMID:Investigations of fluorescent peptides and lipofuscins of human intervertebral disc relating to atherosclerosis. 120 Nov 51

Insufficiencies of the circulatory system and increasing transport losses in pigs as well as analogies with respect to atherosclerosis of men and swine were the motives for a broad statistical investigation of important characteristics of the circulatory system in a big population of female German landrace pigs, fattened as progeny groups under identical conditions in a testing station and slaughtered at 100 kg weight. As the most essential results, highly significant seasonal and genetical influences on several traits are to be mentioned, and some meaningful correlations between them: Plasma cholesterol, ceruloplasmin and hematocrit showed markedly lower levels in the summer and increased values in the cold season; the thickness of the intima (aorta and arteria pulmonalis) was quite distinctly greatest in the spring, this phenomenon being almost exactly paralleled by augmented amounts of copper and iron in the aortic wall. Increased heart weights were again found in the cold, decreased ones in the warm seasons. On average, bigger hearts and vessels were accompanied by higher elastin contents of the aorta, but these contents stood in very significant negative correlation to the ash content and the amounts of certain mineral components (Ca, Mg and P) of the vessel wall, especially to the ash percentage of the elastic fibers. This indicates that calcifying and mineralizing processes in the wall obviously take place at the cost of the elastic components. The estimation of heritabilities in half and full sibs revealed with h2 = 60% high henetic influences on the elastin content of the aorta and equally so on the ash percentage of elastic fibers. Future investigations must correlate these findings with direct measurements of biomechanical and rheological properties of the vessels.
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PMID:[The exogenous and genetic components of some vessel wall characteristics in the pig (author's transl)]. 122 Jun 64

The purpose of our experiments was to clarify the relationship between the susceptibility to atherosclerosis and chemical composition in the human cerebral, coronary arteries and aorta, and the concentration and composition of human arterial intimal elastic tissues were measured. In the cerebral arteries, the concentration of hot alkali-insoluble elastin was higher than that of the coronary arteries and aortas, and gradually decreased with age. Age-related changes of the elastin in the coronary arteries were quite small. The total polar amino acids and crude ash contents of arterial elastins were affected by age and treatment of elastic tissue wheteher or not EDTA-decalcification was applied prior to alkali-extraction. No significant differences in the amino acid composition of elastin was founded between the cerebral, coronary and aortic intimas and no significant changes to elastin, and or collagen, which can explain the slow development of atherosclerosis in the cerebral artery, were founded. Therefore, from these results, the slower development rate of cerebral atherosclerosis, as compared with other arteries, can not be sufficiently concluded.
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PMID:Chemical comparison of intimal elastin in the human cerebral and coronary arteries and aorta. A preliminary note. 123 41

External jugular veins that had been subjected to the hemodynamic stresses produced by experimental arteriovenous anastomosis developed 2% increased total protein contents and 17% increased collagen contents. When the stressed veins were homogenized and extracted with saline solutions, statistically significant increases in the saline-soluble proteins and in the saline-soluble collagen (87% and 267%, respectively) were observed. Increased amounts of low molecular weight peptides were found in the extracts. A fraction of these peptides could be degraded by Clostridium collagenase. The saline extract also contained proteins which resembled by their amino-acid composition the acidic structural proteins of the connective tissues. Additonally, in 3 dogs so tested, changes were found in the hydroxylation and glycosylation of lysine from gelatin extracts as well as in the lysine and desmosine contents of the insoluble elastin fractions. This is the first demonstration of a hemodynamically induced increase in the saline solubility of connective tissue proteins in the absence of dietary manipulations.
Atherosclerosis
PMID:Hemodynamically-induced increase in soluble collagen in the anastomosed veins of experimental arteriovenous fistulae. 126 60

In this review, we have highlighted pivotal cellular and molecular events in the initiation and progression of atherosclerosis. Key components of lesion initiation are an enhanced focal intimal influx and accumulation of lipoproteins, including LDL in hemodynamically determined lesion-prone areas, focal monocyte-macrophage recruitment, intimal generation of ROS, and oxidative modification of lipoproteins (including LDL [Ox-LDL]). Modified lipoproteins are taken up by the non-downregulating macrophage scavenger receptor, with foam cell formation and the development of the so-called fatty streak. One transitional event in lesion progression is foam cell necrosis, likely attributable to the cytotoxicity of both intimal free radicals and Ox-LDL, with development of an extracellular metabolically inert lipid core. Another is the migration to and proliferation within the intima of medial SMCs, leading to the synthesis of plaque collagens, elastin, and proteoglycans. Mural thrombosis plays a significant role in the late-stage progression of lesions. Regression of lesions is considered a function of the dynamic balance among components of initiation, progression, plaque stabilization, and removal of plaque constituents--the so-called regression quartet. Here, we critically examine how components of diabetes mellitus might impact not only lesion development, but also lesion regression. It is concluded that some components of diabetes mellitus augment key mechanisms in lesion initiation and progression and will likely retard the processes of plaque regression. Specifically, we focus on the various influences of diabetes mellitus on lipoprotein influx and accumulation, free radical generation and Ox-LDL, monocyte-macrophage recruitment, thrombosis and impaired fibrinolysis, and the reverse cholesterol transport system. The importance of nonenzymatic protein glycosylation in modifying a number of these processes is emphasized.
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PMID:Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. 139 13

Smooth muscle cells (SMC) were obtained by outgrowth of human aortic explants from abdominal aortic aneurysm (AAA) patients, aortic occlusive disease (AOD) patients, and transplant donors (controls). Specimens were incubated with medium alone or medium with either elastin-derived peptides (EDP, 5 micrograms/mL) or low-density lipoproteins (LDL, 5 micrograms/mL). Elastase activity (ng/mg total protein) was assayed from 4-week-old cultures. Control aortas obtained from patients significantly younger secrete an increased amount of elastase at baseline compared with AOD and AAA patients (p less than 0.05). Elastin-derived peptides caused a significant increase in elastase secretion in all groups. The increase in elastase secretion in response to EDP in AAA patients was significantly higher compared with AOD or control. Low-density lipoprotein had no effect on SMC elastase secretion. These data suggest that (1) aortic SMCs secrete elastase in response to EDP, (2) SMC elastase is age dependent, and (3) AAA SMC secrete an abnormally high amount of elastase compared with AOD and control aortas in response to EDP. Like the neutrophil, the SMC is highly responsive to the degradation products of elastin and in AAA patients secrete significantly increased amounts of elastase in response to the breakdown products of atherosclerosis.
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PMID:Smooth muscle cell elastase, atherosclerosis, and abdominal aortic aneurysms. 141 82

Ageing and degenerative changes of the human aorta are associated with medial thinning and a reduced dry weight content of elastin. The metabolic stability of cross-linked elastin was investigated by measuring the accumulation of D-aspartate with ageing in insoluble elastin isolated from human aorta. D-Aspartate accumulation in elastin was compared with D-aspartate accumulation in aortic collagen and an elastin bound glycoprotein fraction. The D-aspartate content of elastin, purified from infrarenal aorta; increased linearly with age from 3% of the total aspartate in youth to 13% in the mid 80s. In contrast the D-aspartate content of aortic collagen remained invariant (3-5% of the total aspartate) from youth to old age. The apparent first order rate constant for the racemization of L-aspartate in elastin was 1.14 x 10(-3). The D-aspartate content of the elastin bound glycoproteins increased by only a small amount, from 3% in the mid 30s to 6% in the mid 80s. These results argue for the metabolic stability of aortic elastin as compared with the fibrillar collagens of the human aorta. Both the rate of racemization and the specific accumulation of D-aspartate in elastin, but not collagen, indicates that mature cross-linked elastin is not synthesized in the adult aorta.
Atherosclerosis 1992 Dec
PMID:On the accumulation of D-aspartate in elastin and other proteins of the ageing aorta. 146 64


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