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)

The foam cell is viewed as a specific component of the atherosclerotic plaque found in human or experimentally induced in the animal. A study using light microscopy (staining with Sudan III) and electron microscopy was performed on cell cultures derived from rat aortic media. Sudanophilic and electron transparent vacuoles were observed in vitro in 11 week cultures. The sudanophilic cells were either scattered or crowded in clusters; some of them were found in a mitotic phase. Different serums were applied to the cultures starting from the 6th week: either calf serum (continuing the previous treatment), or normocholesterolemic rat serum (NCRS) or hypercholesterolemic rat serum (HCRS). Sudanophilic cells were observed more frequently in the cultures on exposure to HCRS than to NCRS (p less than 0.05). Thus it was possible to induce the formation of foam cells in vitro in cultures of arterial tissue derived from the rat, which is known to be resistant to atherosclerosis.
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PMID:[Formation of xanthomatous cells in vitro from the aortic media of the rat]. 6 56

A number of soluble proteins contained in human aortic intimal tissue was extracted into buffered saline (pH 7.4) and identified and quantitated by immunoelectrophoresis and immunodiffusion. The proteins included IgA, IgG, IgM, B1C (C3), alpha 1-antitrypsin, alpha 2-macroglobulin, fibrinogen, albumin, LDL, HDL, alpha 1-acid glycoprotein, beta 2-glycoprotein, transferrin and ceruloplasmin. The concentration of soluble proteins was significantly higher in the atherosclerotic intima than in the normal intima. The diseased intima also contained a small amount of tissue-bound IgG, IgA and B1C which was extractable with citrate buffer at pH 3.2. The vascular band IgG, and B1C were shown by enzymatic and immunohistochemical studies to be closely associated with the collagenous tissue of the plaque. The Ig contained in the atherosclerotic plaque may be derived in part from the biosynthesis of Ig by the artery, since the incorporation of 14C-labeled leucine into IgG by the atheromatous plaque was demonstrable by radioimmunoelectrophoresis. In contrast to the diseased artery, the normal artery did not synthesize IgG and did not contain vascular bound IgG or complement. However, the normal artery was capable of fixing IgG and B1C eluted from the diseased artery. The present studies suggested that the IgG contained and synthesized by the plaque might represent an immune response to an endogenous or exogenous antigen closely associated with plaque collagen. IgG and B1C either alone or in the form of an immune complex also may play an important role in phagocytosis in the plaque and thereby influence the course of atherosclerosis. The proteolytic inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, found in relatively high concentrations in the plaque, could enhance fibrosis of the lesion because of thier known inhibitory effects on collagenase and elastase.
Atherosclerosis 1979 Dec
PMID:Soluble proteins in the human atherosclerotic plaque. With spectral reference to immunoglobulins, C3-complement component, alpha 1-antitrypsin and alpha 2-macroglobulin. 9 93

Aortic pulse wave velocity was determined in Macaca fascicularis monkeys fed either atherogenic or control diets for 36 months. The foot-to-foot velocity and apparent phase velocities of the second through seventh Fourier harmonics at a given diastolic pressure in the atherosclerotic monkeys were 1.5 to 2.0 times the values for the control animals. More than 80% of the aortic intimal surface of the atherosclerotic monkeys was covered with fibrous or fatty plaque, which approximately doubled wall thickness and wall thickness to radius ratio. Angiochemical evaluations showed no difference in collagen or elastin concentration (as a fraction of lipid and mineral-free dried aorta), but the atherosclerotic aortas were 1.5 to 2.0 times that of control in collagen and elastin content (defined as the absolute quantity beneath a square centimeter of intimal surface). Total cholesterol and calcium concentrations in the atherosclerotic aortas were more than 10 times the values for the control aortas. The static circumferential distensibility of the excised atherosclerotic aortas was significantly less than control, but there was no difference in incremental (Young's) modulus of elasticity. The in vitro pressure-strain elastic modulus of the atherosclerotic aortas was more than twice that of control, which was predicted from the enhanced wave velocity. The significantly increased stiffness of the atherosclerotic arteries appeared to be due mainly to the increased wall thickness caused by the atherosclerotic plaques rather than to material changes described by Young's modulus. Extensive medial damage, however, also was present and could have had a major influence on stiffness. Atherosclerosis therefore can result in increased aortic stiffening, detectable by pulse wave velocity, even if there is no change in the overall Young's modulus of elasticity.
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PMID:Aortic pulse wave velocity, elasticity, and composition in a nonhuman primate model of atherosclerosis. 9 6

Aortic atherosclerosis is minimal in normal Macaca nigra; development of atherosclerosis correlates with increasing severity of diabetes mellitus. The extent of aortic involvement (plaque plus sudanophilia) was quantified and compared with metabolic and clinical parameters. Increasing atherosclerosis correlated with decreasing ability to clear glucose in a tolerance test (P less than 0.01), decreasing insulin (P = 0.02), and increasing glucose (P less than 0.01) and triglycerides (P less than 0.01). A diabetic index, established as a summation of several metabolic measurements, correlated with atherosclerosis at P less than 0.001. On the average, involvement of the thoracic aorta was about 3-fold greater than in the abdominal portion; involvement reached over 40% in severely diabetic monkeys. Atherosclerosis development is unique in these monkeys since they consume a natural ration low in fat and cholesterol. Serum cholesterol did not correlate with diabetes or artherosclerosis. Increasing age alone was associated with slight sudanophila, some intima-media thickening, and occasional small lesions. However, only with increasing severity of diabetes was there significant atherosclerosis.
Atherosclerosis 1979 Aug
PMID:Aortic atherosclerosis in normal and spontaneously diabetic Macaca nigra. 11 65

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

Proline hydroxylase activity and collagen content were determined in atherosclerotic plaque, fatty streak, and normal tissue from aortas of White Carneau pigeons with naturally-occurring of cholesterol-aggravated atherosclerosis. Little increase in collagen content or proline hydroxylase activity occurred in fatty streaks or plaques from birds with cholesterol-aggravated atherosclerosis. This is consistent with the morphologic observation of the presence of little or no "fibromuscular cap" in these cholesterol-aggravated lesions. Both normal and plaque tissue from arotas of birds with naturally-occurring atherosclerosis contained more collagen than did similar tissues from control birds or birds with cholesterol-aggravated lesions. The largest proportion of this increase in collagen content probably represented an age effect since it occurred in normal as well as atherosclerotic tissue. Plaques from aortas of birds with naturally-occurring atherosclerosis did contain, however, significantly more collagen than normal tissue from the same aortas. This is consistent with the presence of a prominent "fibromuscular cap" in these naturally-occurring lesions. Proline hydroxylase activity was less in these lesions than in normal tissue from the same aortas. Consequently increased proline hydroxylase activity and collagen content are not greatly altered in association with development of cholesterol-aggravated atherosclerotic lesions in pigeons. On the other hand, well-developed naturally-occurring lesions contained increased concentrations of collagen but showed no increase proline hydroxylase activity. This is not to say though, that active collagen synthesis and presukably increased proline hydroxylase activity did not take place at some point in the development of these naturally-occurring lesions.
Atherosclerosis
PMID:Proline hydroxylase activity and collagen content of pigeon aortas with naturally-occurring and cholesterol-aggravated atherosclerosis. 16 23

Elastin preparations were isolated from human thoracic aorta, from atherosclerotic and from grossly normal regions. A relatively mild procedure was used to avoid hot alkaline extraction and autoclaving. The elastase digest of the aortic elastin was chromatographed on a Sephadex G-100 column and separated into two fractions: A (larger molecular weight) and B (smaller molecular weight). The ratio of fraction A to total aortic elastin increased with age and the development of the atherosclerosis. Amino acid and sugar analyses showed that fraction A consistently contained more polar amino acids, hexose, hexosamine and L-fucose, and less sialic acid, in comparison with fraction B. Part of the elastin preparation was incubated with human low-density lipoprotein; a considerable amount of lipid, especially cholesterol, was transferred from the lipoprotein to the elastin. Estimation of protein and cholesterol in fractions A and B of the elastase hydrolyzate of incubated elastin showed that most of the cholesterol taken up by elastin had been in fraction A. The increased proportion of fraction A in aortic elastin derived from plaque areas appeared responsible for the marked lipid-binding capacity of plaque elastin.
Atherosclerosis 1977 Oct
PMID:Elastin sub-fraction as binding site for lipids. 19 4

Experimental atherosclerosis in rabbits induced by feeding a standard atherogenic diet for 4 months resulted in an increased sensitivity of platelets to the proaggregatory action of collagen and ADP. Treatment with dipyridamole (3 x 10 mg/day i.m.) for 4 weeks normalized platelet loss in atherosclerotic rabbits and abolished the increased sensitivity to proaggregatory collagen, but not to ADP. Dipyridamole treatment lowered basal as well as PGI2-induced cAMP levels below values seen in platelets from normal rabbits, but the stimulation by PGI2 relative to basal cAMP levels was not affected or even increased by dipyridamole treatment. Dipyridamole did not affect the increased sensitivity of platelets from atherosclerotic rabbits to the antiaggregatory action of PGI2, indicating that dipyridamole decreased absolute cAMP levels, probably due to reduction of the adenine nucleotide pool in platelets without affecting the adenylate cyclase function. Dipyridamole enhanced atherosclerotic plaque formation in arterial walls. Basal as well as PGI2-stimulated cAMP content was lower in homogenates from atherosclerotic than from normal aortic tissue. Dipyridamole-treated animals showed a further decrease in basal as well as PGI2-stimulated cAMP content of the aortic tissue, suggesting that this decrease in cAMP content may be linked to the enhanced proliferative activity seen in artherosclerotic plaque formation.
Atherosclerosis 1979 Jul
PMID:Effects of dipyridamole in experimental atherosclerosis. Action on PGI2, platelet aggregation and atherosclerotic plaque formation. 22 6

The interaction of lipoproteins and arterial connective tissue macromolecules was studied using human atherosclerotic plaque tissues. After extraction with 0.15 M NaCl, the tissues were repeatedly digested with collagenase followed by elastase. The collagenase-solubilized lipoprotein--GAG complexes were isolated by gel-filtration and ultracentrifugation and analyzed for lipids, GAG and protein. While extraction by 0.15 M NaCl released only about 13% of the total cholesterol from the tissues, subsequent digestions by collagenase and elastase yielded 60% and 17% cholesterol, respectively. Both 0.15 M NaCl and collagenase treatment released equal amounts of GAG and accounted for 84% of the total GAG. Immunologically, lipoproteins resembled serum apoB-containing lipoproteins. Bio-Gel A-50m column chromatography of collagenase-extracted materials gave a single peak which contained lipoproteins of 1.006 and 1.063 floating densities, GAG and hydroxyproline. Hyaluronic acid (HA) and chondroitin 6-sulfate were identified; HA was the major GAG. Although the precise nature of the interaction of arterial connective tissue components with lipoproteins is not completely understood, isolation of such complexes indicates the importance of these macromolecules in sequestration of lipoproteins.
Atherosclerosis 1979 Oct
PMID:Collagenase-solubilized lipoprotein--glycosaminoglycan complexes of human aortic fibrous plaque lesions. 22 69

Cerebral arteries from 65 human subjects were examined by immunofluorescence, using antisera against human fibrinogen and low density lipoprotein (LDL). Deposition of fibrinogen and LDL was most frequent at the bifurcation of the middle cerebral arteries and least in the basilar arteries in all age groups. In general, deposition of LDL was associated with deposition of fibrinogen, and lone deposition of LDL in the absence of fibrinogen was only rarely seen. Fibrinogen was scattered in the intercellular spaces, and located in the inner layer or edges of the thickened intima of the bifurcation with increasing plaque formation. Fibrinogen was observed even in the subendothelial region of the uninvolved intima at the bifurcations. LDL was present in the cytoplasm of the endothelial cells in the earliest stage, and it increased in the extracellular stroma with increase in intimal thickening, corresponding closely to the distribution of perifibous oil-red-O-stained lipids. No LDL was detected in the uninvolved intima. The observations suggest that deposition of fibrinogen in the intima might precede LDL deposition and possibly play a more important role than LDL in the development of atherosclerotic lesions in the cerebral arteries, especially in their early stage. Severe atherosclerosis at the bifurcations may be in part due to increased permeation of these plasma proteins, possibly as a result of hemodynamic stress.
Atherosclerosis 1979 Oct
PMID:Fibrinogen and low density lipoprotein in the development of cerebral atherosclerosis. 22 73


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