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)

1. There is a familial tendency to abdominal aortic aneurysms. We have followed up a previous report of a weak association between the haptoglobin 2-1 phenotype and aortic aneurysm and investigated polymorphisms of the haptoglobin gene and neighbouring cholesterol ester transfer protein gene on the long arm of chromosome 16 in patients with atherosclerotic abdominal aortic aneurysm, patients with stenosing aortic atherosclerosis and healthy control subjects. The protein polymorphism of haptoglobin results from variant alpha-chains, alpha 1 and alpha 2, the phenotype nomenclature describing the two alpha-chains. We have also investigated whether the different haptoglobin phenotypes influence the degradation of aortic connective tissue. 2. The frequency of the haptoglobin alpha 1 allele was increased in patients with aneurysms compared with healthy control subjects (0.51 versus 0.35, P less than 0.05). Patients homozygous for the alpha 2 allele had the highest mean age at aneurysm resection. The frequency of a rare polymorphism at the cholesterol ester transfer protein locus was also increased in aneurysm patients (0.15 versus 0.05 in control subjects, P less than 0.01). These two genetic markers appear to act independently. Haptoglobins containing an alpha 1-chain accelerated two- to four-fold the degradation by elastases of aortic elastin in vitro. 3. Genetic variation in the haptoglobin and cholesterol ester transfer protein genes appears to influence dilatation of the abdominal aorta. Variation at the haptoglobin locus could have a direct effect on the degradation of elastin in atherosclerotic aorta, whereas variation at the cholesterol ester transfer protein locus could affect lipid metabolism and promote atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm. 196 66

Protein extracted from 24 human aortic intimas (6-33 years old) with 9 M urea mixture, were studied after separation by two-dimensional gel electrophoresis (2-DE) and silver staining. The protein composition of normal intima in 4 cases, each without any gross changes in the thoracic aorta, displayed similarity. In each 2-DE protein pattern of these intimas about 150 polypeptide spots were detectable/mg of wet tissue. Major and medium polypeptides were described by relative molecular weight Mr in kilodaltons (kDa) and relative charge Cr. Major proteins found were actin (P44-18; Mr = 44 kDa; Cr = -18), tropomyosin-like proteins (P34-29, P35-28.5, P36-31) and two glycoproteins (G35-21, G35-23.5). Several new major and medium extracellular proteins were demonstrated in fibro-fatty lesions as well as in the lesion-free intimas adjacent to lesion in 3 cases. Many of these proteins appeared to originate from plasma: albumin, IgG, alpha 1-antitrypsin, transferrin, haptoglobin beta-chain, apo A-I, apo A-II, fibrinogen beta-chain, alpha 2-HS glycoprotein and alpha 1-antichymotrypsin. Visual comparison of intimal protein patterns from 17 different cases with varying degree of fatty streaks in the thoracic aorta, showed variability in 2 polypeptides P32-17.8 and P32-19.8 as well as 4 plasma proteins albumin, alpha 1-antitrypsin, transferrin and apo A-I. This study suggests that changes in protein composition may occur in the human aortic intima during the initial histological stages of atherogenesis providing potentially useful markers for their identification and pathophysiological evaluation.
Atherosclerosis 1986 May
PMID:Human aortic intima protein composition during initial stages of atherogenesis. 242 64

Serum lipoprotein(a) (Lp(a)) was serially determined after acute attacks of myocardial infarction and after surgical operations. Acute phase proteins, such as C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antitrypsin and haptoglobin, increased rapidly and markedly after the episodes. Initial values of serum Lp(a) concentrations were almost the same in both groups. Increases in serum Lp(a) levels were also observed during the first few days, with a return to the initial levels after more than 1 month. The periods for reaching maximal levels of acute phase proteins were similar in both groups of patients. On the contrary, the period required for Lp(a) to reach the maximal level in the myocardial infarction group was significantly longer than in the post-operative group. The present study suggests that Lp(a) has the characteristics of an acute phase reactant and may play an important role in recovery from tissue damage.
Atherosclerosis 1989 Aug
PMID:Transient changes of serum lipoprotein(a) as an acute phase protein. 247 92

Arterial intima proteins were extracted by 9 M urea from matching histologically atheroma-free areas of 27 human thoracic aortas of both sexes from younger (15-34) and older (35-82) age groups and studied after separation by high-resolution two-dimensional polyacrylamide gel electrophoresis. Seventeen specific protein groups on each gel were identified according to their relative charges and molecular weights and their distribution in the two age groups compared. Some plasma-derived proteins occurred rarely in young aortas while they were consistently found in those from older cases, i.e., protein group 4 (alpha 1-antichymotrypsin) 1/13 (8%) vs 12/14 (86%), group 7 (haptoglobin beta-chain) 1/13 (8%) vs 13/14 (93%) and groups 6 and 9 (IgG chains) 3/13 (23%) vs 9/14 (64%), respectively. Other plasma-derived proteins such as group 3 (albumin) and 5 (alpha 1-antitrypsin) were identified in all samples of both age groups but their expression in the aortic intima increased with age. Proteins which are typically found intracellularly such as those from groups 11 (actin), 12 (cytoskeleton proteins), and 13 (tropomyosin-like proteins) appeared in samples of intima of both age groups but were less apparent in older specimens. These studies suggest that the changes in aortic intima protein distribution in the absence of atherosclerosis closely correlate with histological changes such as intimal thickening often found with aging, providing new sensitive markers of vascular senescence.
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PMID:Effect of aging on human aortic protein composition. II. Two-dimensional polyacrylamide gel electrophoretic analysis. 406 9

Serum proteins and lipoproteins were determined in 23 menopausal females after surgery for early forms of breast cancer and the results compared with data from a matched group of randomly selected healthy females. The patients were randomly divided into 2 groups, one serving as a control group, the other receiving 40 mg tamoxifen daily for 2 months. Breast cancer patients were found to have significantly higher concentrations of serum cholesterol than controls (7.90 +/- 1.15 vs. 6.87 +/- 1.18 mmol/l, P less than 0.001), which was the result of a 16% higher concentration in LDL cholesterol (P less than 0.05) and a 13% higher concentration in HDL cholesterol (P less than 0.05). During tamoxifen therapy total TG tended to increase, whereas total cholesterol fell. Significant lipoprotein changes were found in the LDL fraction where LDL-TG increased from 0.46 to 0.56 (P less than 0.01) and LDL cholesterol fell from 5.11 to 4.10 mmol/l (P less than 0.001). During tamoxifen therapy haptoglobin and orosomucoid concentrations fell significantly (P less than 0.01), whereas those of alpha-antitrypsin and ceruloplasmin increased (P less than 0.001). Factors such as diet and weight may explain the differences between breast cancer patients and controls. The tamoxifen-induced changes indicate that this anti-oestrogen exerted a mild oestrogen-like effect with regard to protein and lipoprotein metabolism.
Atherosclerosis 1984 Sep
PMID:Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. 649 36

Whole-blood viscosity (measured at 128, 23 and 0.2 s-(1) was significantly increased in 29 females with Raynaud's syndrome, 13 males with vibration-induced Raynaud's syndrome, and 18 males with calf claudication secondary to atherosclerosis, as compared with 50 healthy controls matched for sex, age and smoking habit. Viscosity was higher at low temperature (27 and 22 degrees C) in all three types of vascular disease and, despite symptoms of cold hypersensitivity, patients with Raynaud's syndrome did not show selective hypersensitivity at low temperature. Patients with vascular disease, irrespective of aetiology, also showed an increase in the acute-phase reactants haptoglobin, fibrinogen, and factor VIII antigen, together with reduced fibrinolytic activity and minor activation of platelets. These alterations in viscosity and haemostatic factors in vascular disease are probably related to the degree, rather than the aetiology, of endothelial damage and their cumulative effect may contribute to local stasis and thrombosis, particularly in cold extremities.
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PMID:Hyperviscosity and thrombotic changes in idiopathic and secondary Raynaud's syndrome. 677 75

This study investigated the relationship between serum sialic acid concentration and cardiovascular mortality. Correlations were determined between lifestyle-related coronary heart disease risk markers (cigarette consumption, alcohol consumption, and leisure time physical activity), biological risk markers (apolipoprotein A1, apolipoprotein B, lipoprotein(a), and diastolic blood pressure) on the one hand and the concentration of sialic acid as well as sialic acid-rich acute phase proteins (orosomucoid, haptoglobin, and alpha 1-antitrypsin) on the other. A total of 145 men aged 21-46 years and with a C-reactive protein concentration below 5 mg/l were included. Total sialic acid concentration correlated significantly with apolipoprotein B (r = 0.48), number of cigarettes smoked daily (r = 0.32), and leisure time physical activity (r = -0.23) after adjustment for age and other cardiovascular risk markers. No significant partial correlations were found between serum total sialic acid concentration on the one hand and alcohol consumption, apolipoprotein A1, lipoprotein(a), and diastolic blood pressure on the other. Of the sialic acid-rich glycoproteins, orosomucoid correlated with apolipoprotein B (r = 0.38), haptoglobin with cigarette consumption (r = 0.35) and leisure time physical activity (r = -0.26) and alpha 1-antitrypsin with cigarette consumption (r = 0.18), leisure time physical activity (r = 0.17), alcohol consumption (r = -0.18), and apolipoprotein B (r = 0.21) after adjustment for age and other cardiovascular risk markers.
Atherosclerosis 1993 Nov
PMID:Serum concentrations of total sialic acid and sialoglycoproteins in relation to coronary heart disease risk markers. 750 25

The relation of serum glycoproteins and C-reactive protein (CRP) to severity of coronary atherosclerosis was examined in 133 men and 92 women undergoing coronary angiography. The following serum glycoproteins were determined: alpha 1-antitrypsin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, ceruloplasmin, haptoglobin, fibrinogen, C4b binding protein, and lipoprotein (a) [Lp(a)]. Sex- and age-adjusted levels of alpha 1-antitrypsin, alpha 1-acid glycoproteins, alpha 2-macroglobulin, ceruloplasmin, Lp(a) and CRP were significantly associated with the severity of coronary atherosclerosis as determined by the Gensini score; these associations remained significant even after adjustment for body-mass index, smoking history, hypertension, and total cholesterol, except for Lp(a) (p = 0.075). These findings suggest that certain serum glycoproteins and CRP can serve as independent indicators for the progression of coronary atherosclerosis.
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PMID:Serum glycoproteins and severity of coronary atherosclerosis. 783 94

Heme proteins transport oxygen and facilitate redox reactions. Heme, however, may be dangerous, especially when free in biologic systems. For example, iron released from hemoglobin-derived heme can catalyze oxidative injury to neuronal cell membranes and may be a factor in post-traumatic damage to the central nervous system. We have shown that heme catalyzes the oxidation of low density lipoproteins which can damage vascular endothelial cells. The endothelium is susceptible to damage by oxidants generated by activated phagocytes, and this has been invoked as an important mechanism in a number of pathologies including the Adulte Respiratory Distress Syndrome (ARDS), acute tubular necrosis, reperfusion injury and atherosclerosis. Because of its highly hydrophobic nature, heme readily intercalates into endothelial membranes and potentiates oxidant-mediated damage. This injury is dependent on the iron content of heme and is completely blocked when concomitant hemopexin is added. Ferrohemoglobin, when added to cultured endothelial cells, is without deleterious effects, but if oxidized to ferrihemoglobin (methemoglobin), it greatly amplifies oxidant damage. Methemoglobin, but not ferrohemoglobin, releases its hemes which can then be incorporated into endothelial cells. Cultured endothelial cells, when exposed to methemoglobin but not ferrohemoglobin, cytochrome c or metmyoglobin, potentiate this oxidant injury. Stabilization of the methemoglobin by cyanide, haptoglobin or capture of the heme by hemopexin abrogates this effect. Paradoxically, more prolonged exposure of endothelium to heme or methemoglobin renders them remarkably resistant to oxidant challenge. Endothelium defends itself from heme by induction of the heme degrading enzyme heme oxygenase and the concomitant production of large amounts of the iron binding protein ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. 808 43

Iron-derived reactive oxygen species are implicated in the pathogenesis of various vascular disorders including atherosclerosis, vasculitis, and reperfusion injury. The present studies examine whether heme, when liganded to physiologically relevant proteins as in hemoglobin, can provide potentially damaging iron to intact endothelium. We demonstrate that reduced ferrohemoglobin, while relatively innocuous to cultured endothelial cells, when oxidized to ferrihemoglobin (methemoglobin), greatly amplifies oxidant (H2O2)-mediated endothelial-cell injury. Drawing upon our previous observation that free heme similarly primes endothelium for oxidant damage, we posited that methemoglobin, but not ferrohemoglobin, releases its hemes that can then be incorporated into endothelial cells. In support, cultured endothelial cells exposed to methemoglobin--in contrast to exposure to ferrohemoglobin, cytochrome c, or metmyoglobin--rapidly increased their heme oxygenase mRNA and enzyme activity, thereby supporting heme uptake; ferritin production was also markedly increased after such exposure, thus attesting to eventual incorporation of Fe. These cellular methemoglobin effects were inhibited by the heme-scavenging protein hemopexin and by haptoglobin or cyanide, agents that strengthen the liganding between heme and globin. If the endothelium is exposed to methemoglobin for a more prolonged period (16 hr), it accumulates large amounts of ferritin; concomitantly, and presumably associated with iron sequestration by this protein, the endothelium converts from hypersusceptible to hyperresistant to oxidative damage. We conclude that when oxidation of hemoglobin facilitates release of its heme groups, catalytically active iron is provided to neighboring tissue environments. The effect of this relinquished heme on the vasculature is determined both by extracellular factors--i.e., plasma proteins, such as haptoglobin and hemopexin--as well as intracellular factors, including heme oxygenase and ferritin. Acutely, if both extra- and intracellular defenses are overwhelmed, cellular toxicity arises; chronically, when ferritin is induced, resistance to oxidative injury may supervene.
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PMID:Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. 841 93


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