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

Although it has long been thought that environmental toxins may play an underlying role in vascular diseases such as atherosclerosis, this concept is not supported by any clear-cut experimental evidence of toxic metabolism by cardiovascular enzymes. In this study, we demonstrate that allylamine, a selective cardiovascular toxin in vivo, is actively metabolized in vitro by a purified vascular enzyme (semicarbazide-sensitive amine oxidase), which has been localized recently to vascular smooth muscle cells. Oxidative deamination of allylamine to a highly toxic aldehyde, acrolein, was blocked through enzyme inhibition by semicarbazide-sensitive amine oxidase suggests that this vascular enzyme's physiological role may include metabolism of exogenous amines.
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PMID:A role for a new vascular enzyme in the metabolism of xenobiotic amines. 210 85

A review is presented of the monoamine-oxidizing enzymes with special reference to the activity of benzylamine oxidase (BzAO) in human tissues. Methods of study of amine oxidases, properties (chiefly of BzAO) and some problems concerning substrate and inhibitor specificity and multiple forms of monoamine oxidase (MAO) are surveyed. The substrate specificity of human plasma BzAO is compared with that of amine-oxidizing enzymes in plasma or serum of other species. Correlations of plasma BzAO and platelet MAO activity with clinical findings are discussed. The distribution of amine oxidase activities in solid human tissues is reviewed, in particular BzAO in blood vessels and richly-vascularized tissues, as well as kinetic constants and altered patterns of activity of BzAO in human atherosclerosis. Activities of the amine oxidases in non-vascular smooth muscle, in cultured cells, and in various tissues related to human gestation, are discussed. The present knowledge of BzAO is discussed in terms of its possible clinical relevance to several human disease states, and the importance of the enzyme in the human body.
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PMID:Mammalian monoamine-oxidizing enzymes, with special reference to benzylamine oxidase in human tissues. 644 76

We studied histamine metabolism, i.e., histidine decarboxylase (HD)-mediated synthesis and histaminase-mediated catabolism, in relation to intracellular histamine content in both aortic endothelial and subjacent smooth muscle cells of control and diabetic rats. Diabetes was induced by a single jugular vein injection of streptozotocin (55 mg/kg in acidified saline, pH 4.5), and animals were held for either 2 or 4 weeks following overt manifestation of diabetes. An additional 4-week diabetic group received insulin (Iletin NPH, 10 U per 24 hour) during the last week. With respect to control values, the histamine content of aortic endothelial cells increased 138%, HD activity increased 250%, and histaminase activity decreased 50% over the 4-week period. In subjacent smooth muscle cells, the histamine content increased in excess of 150%, HD activity increased more than 300%, and histaminase activity decreased in excess of 30%. Insulin treatment for the last week resulted in complete reversal of all these changes. These results support the concept that a large vessel response similar to the microcirculatory prolonged phase of inflammation occurs in experimental diabetes, a change similar to that occurring in experimental atherosclerosis. They also indicate that both synthetic and catabolic changes occur in histamine metabolism under these conditions, changes that alter arterial wall histamine pools, and suggest that insulin administration under conditions of experimental diabetes may modulate aortic histamine metabolism and the resultant intraaortic histamine pools.
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PMID:Aortic endothelial and smooth muscle histamine metabolism in experimental diabetes. 680 15

The authors studied the activity of blood serum amine oxidase in patients with atherosclerosis obliterans and endarteritis obliterans. It was found that amine oxidase activity exceeded the normal value. 2.6 times in patients with stage 1-2 atherosclerosis obliterans and was reduced by more than 12 times in patients with stage 3-4 of the disease. The activity of the enzyme was absent in patients with endarteritis obliterans, whatever the stage of limb ischemia. On the basis of the obtained facts, the authors voice a new opinion on the nature of hypercatecholaminemia in obliterative diseases and suggest a new trend in the treatment of chronic ischemia of the limbs-activation of the processes of catabolism of vasoconstrictive biogenic amines.
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PMID:[Effectiveness of pathogenetic treatment of arterial obliterative diseases of the extremities]. 808 43

Methylamine can be converted by semicarbazide-sensitive amine oxidase (SSAO) to formaldehyde and hydrogen peroxide, which have been proven to be toxic towards cultured endothelial cells. We investigated whether or not these deaminated products from methylamine can exert potentially hazardous toxic effects in vivo. Long lasting residual radioactivity in different tissues was detected following administration of [14C]-methylamine in the mouse. Approximately 10% of the total administered radioactivity could even be detected 5 days after injection of [14C]-methylamine. Eighty percent of the formation of irreversible adducts can be blocked by a highly selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A). The residual radioactivity was primarily associated with the insoluble tissue components and the soluble macromolecules. Radioactively labelled macromolecules were fragmented following enzymatic proteolysis. Results suggest that the formaldehyde derived from methylamine interacts with proteins in vivo. In the streptozotocin-induced diabetic mice, both SSAO activity and the formation of residual radioactivity were found to be significantly increased in the kidney. Chronic administration of methylamine enhances blood prorenin level, which strongly suggests that uncontrolled deamination of methylamine may be a risk factor for initiation of endothelial injury, and subsequent genesis of atherosclerosis.
Atherosclerosis 1996 Feb
PMID:Formaldehyde produced endogenously via deamination of methylamine. A potential risk factor for initiation of endothelial injury. 864 60

The mouse is known to be highly resistant to atherosclerosis. However, some inbred mouse strains are vulnerable to atherosclerosis when they are fed a high-cholesterol, high-fat diet. Increased deamination of methylamine (MA) and the subsequent production of formaldehyde has been recently shown to be a potential risk factor of atherosclerosis. In the present study semicarbazide-sensitive amine oxidase (SSAO)-mediated MA turnover in C57BL/6 mouse, a strain very susceptible to atherosclerosis, has been assessed in comparison to a moderate, i.e. BALB/c, and resistant, i.e. CD1, mouse strains. Kidney and aorta SSAO activities were found to be significantly increased in C57BL/6 in comparison to BALB/c and CD1 mice. A significant increase of urinary MA and formaldehyde were detected in C57BL/6. [14C]MA following intravenous injection would be quickly metabolized by SSAO. The labeled formaldehyde product would cross link with proteins. C57BL/6 exhibits significantly higher labeled protein adducts than BALB/c and CD1 in response to [14C]MA. The results indicated that mice vulnerable to atherosclerosis possess an increased SSAO-mediated MA turnover. The increase of production of formaldehyde, possibly other aldehydes, may induce endothelial injury or be chronically involved in protein cross-linking and subsequent angiopathy.
Atherosclerosis 1998 Oct
PMID:Endogenous formaldehyde as a potential factor of vulnerability of atherosclerosis: involvement of semicarbazide-sensitive amine oxidase-mediated methylamine turnover. 986 79

Allylamine (AA) is a cardiovascular toxin that causes lesions resembling atherosclerosis in several mammalian species. AA's toxic effects are thought to be exerted through its conversion to acrolein (AC), a potent electrophilic alkylating agent and atherogen. Semicarbazide sensitive amine oxidase (SSAO) catalyzes the oxidation of AA to AC. Glutathione S-transferases (GST) can catalyze the first step of detoxification of AC to mercapturic acid. Our previous studies suggest that the isozyme rGST8-8 is a principal defense against electrophilic stress exerted by alpha,beta-unsaturated carbonyls such as AC. In the present studies, we use cultured rat vascular smooth muscle cells (VSMC) to examine the relative roles of SSAO and rGST8-8 in the cytotoxic effects of the atherogens, AA and AC. Exposure derived AA-resistant cells (VSMC-AA) were 3.5-fold more resistant to AA when compared to VSMC and 1.8-fold more resistant to acrolein. SSAO activity was 2-fold higher in VSMC-AA than in VSMC. Consistent with the role of SSAO in biotransformation of AA, the SSAO inhibitor semicarbazide (SC; 100 microM) provided nearly complete protection from AA to both VSMC-AA and VSMC. As expected, SC did not affect the cytotoxicity of AC. Pretreatment with 100 microM sulfasalazine (SS), a GST inhibitor, potentiated AA and AC toxicity in both VSMC-AA and VSMC, indicating a protective role of GST. Catalytic efficiency (K(cat)/K(m)) of GSTs was higher toward 4-hydroxynonenal (4-HNE) (0.65 mM(-1) s(-1)) than toward 1-chloro-2, 4-dinitrobenzene (CDNB) (0.14 mM(-1) s(-1)) for VSMC. In VSMC-AA, K(cat)/K(m) was increased 4.1-fold toward CDNB (0.58 mM(-1) s(-1)) and 6-fold toward 4HNE (3.9 mM(-1) s(-1)) when compared to VSMC, indicating a preferential increase in VSMC-AA of GST isozymes which utilize alpha,beta-unsaturated carbonyls. Western blots confirmed induction of rGST8-8 in VSMC-AA. Expression of recombinant mGSTA4 (the mouse homolog of rGST8-8) in VSMC caused a 1.6-fold increase in resistance to AA and AC. This resistance was fully reversed by 50 microM SS. Our results demonstrate that GSTs are an important defense against electrophilic atherogens and that isozymes with high activity toward alpha,beta-unsaturated carbonyls are particularly important in the vascular wall.
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PMID:Role of glutathione S-transferase 8-8 in allylamine resistance of vascular smooth muscle cells in vitro. 1040 32

We examined the effect of glycemic control on the plasma plant sterol levels (a measure of cholesterol absorption efficacy) and the plasma post-heparin diamine oxidase (DAO) activity (a measure of intestinal mucosal mass) in type 1 diabetes. The plasma plant sterol levels (mmol/mol of cholesterol) and the DAO activities after 30 U/kg of intravenous heparin were determined in age- and sex-matched three groups (12 type 1 diabetic patients undergoing conventional insulin therapy, ten patients undergoing intensive insulin therapy, and ten normal subjects). All patients continued their indicated insulin regimen for 14 days with a weight-maintaining energy restricted diet. The conventional group showed a significant higher (p < 0.001) level of the fasting plasma glucose (FPG) or the glycated albumin (GA), a higher (P < 0.01) DAO activity (2-fold of the peak level), which was observed 10-30 min after the heparin injection, and a higher (P < 0.01) plasma plant sterol levels (1.5-fold) compared with those in the other two groups, respectively. The DAO activity 30 min after the heparin injection significantly correlated with either the glycated albumin (GA) concentration or the plant sterol levels in all subjects. Furthermore, the acute glycemic control by the changes of insulin regimen from conventional to intensive showed a significant reduction of the DAO activity and plant sterols in the same patients. These results suggest that glycemic control in part relates to the intestinal adaptation to cholesterol absorption efficacy in type 1 diabetes.
Atherosclerosis 1999 Aug
PMID:Effect of glycemic control on plasma plant sterol levels and post-heparin diamine oxidase activity in type 1 diabetic patients. 1048 68

Recent data suggest that elevated serum semicarbazide-sensitive amine oxidase activity (SSAO) may cause endothelial injury. Formation of cytotoxic metabolites (especially formaldehyde) and increased oxidative stress might lead to initiation or progression of atherosclerosis. Effective and selective inhibitors of human SSAO might exert cytoprotective effect on endothelial cells. To compare the inhibitor sensitivity of human serum and vascular tissue SSAO enzyme, the inhibitory effect of semicarbazide and MDL 72974A was investigated. Serum and vascular SSAO activity has been determined using 14C-benzylamine as a substrate. The IC50 values of semicarbazide were estimated to be 5x10(-3) M and 5x10(-4) M for SSAO from human serum and saphenous vein, respectively. MDL 72974A amine oxidase inhibitor was more than thousand times more effective than semicarbazide. The IC50 values were 10(-7) M and 10(-8) M for SSAO from human serum and saphenous vein, respectively. This finding supports the hypothesis that soluble and membrane-bound vascular SSAO enzymes might have similar structure.
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PMID:Inhibitor sensitivity of human serum and vascular semicarbazide-sensitive amine oxidases. 1106 Dec 16

The recent discovery that fibrinogen binds to chylomicrons in gastrointestinal lymph has prompted a new rationale regarding the arterial deposition of postprandial lipids, i.e., dietary fat. According to this new rationale, fibrinogen bound to chylomicrons in the gastrointestinal lymph renders those lipid particles and/or their remnants an adhesive potential, even before the particles reach the arterial system. It is proposed that such an adhesive potential, if realized in the vicinity of the arterial wall, can contribute to the nucleation and growth of atherosclerotic plaques, especially during and immediately following a fat-rich meal. Arguments in support of this proposal are made based on the proximity of the lymph outflow tract to the arteries most susceptible to atherosclerosis, and on the tissue distributions and activities of heparin, diamine oxidase, and lipoprotein lipase. This new rationale reconciles existing theories on atherosclerosis, and it also suggests novel means by which to prevent/treat the disease.
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PMID:Fibrinogen-coated chylomicrons in gastrointestinal lymph: a new rationale regarding the arterial deposition of postprandial lipids. 1244 16


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