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 blood levels of 6-keto-PGE1 alpha and thromboxane B2 were measured in the coronary sinus of 15 males during and just after a spontaneous myocardial ischemic episode. The comparison was made in 30 males with coronary heart disease in the presence of exercise-induced angina in whom coronary sinus blood samples were taken during myocardial ischemia provoked by pacing and 6 males suffering from cardialgias without signs of coronary atherosclerosis. The patients with spontaneous anginal attacks had lower baseline 6-keto-PGE1 alpha (179.0 +/- 47.8 pkg/ml) than those with exercise-induced angina (336.0 +/- 65.7 pkg/ml; p less than 0.1). This difference became greater during ischemia (165.0 +/- 49.0 and 350.0 +/- 69.5 pkg/ml, respectively, p less than 0.05) and just after its elimination (166.0 +/- 48.7 and 413.0 +/- 76.0 pkg/ml, respectively, p less than 0.05). Coronary sinus blood thromboxane B2 levels were not substantially different in the presence or absence of myocardial ischemia. Thus, a decrease in the prostacyclin-forming function of the coronary endothelium plays a definite role in the genesis of spontaneous myocardial ischemic episodes.
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PMID:[Coronary sinus blood thromboxane and prostacyclin in spontaneous myocardial ischemia]. 179 81

Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium-dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis.
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PMID:Endothelium-derived relaxing and contracting factors. 187 96

The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall (PLP) on serum lipids. Plasma lipid peroxides (LPO), TXB2, and 6-keto-PGF1 alpha in cholesterol-fed rabbits have been investigated. Oral administration of nifedipine (15 mg/kg.d), diltiazem (30 mg/kg.d), and PLP (5 g/kg.d) caused 60.8%, 45.2%, and 74.2% reduction in the area of atherosclerosis in the aorta respectively. The levels of plasma LPO and TXB2 and the contents of cholesterol, phospholipid, and calcium in the intimal-media of the aorta in the treated groups were significantly lower than those in the cholesterol group, but the level of plasma 6-keto-PGF1 alpha in the treated groups was significantly higher. The appearance of cholesterol-induced TXB2 elevation and 6-keto-PGF1 alpha decrease in the treated groups was delayed. There are positive correlation between plasma TXB2 and the followings: serum lipids, plasma LPO, and the content of calcium in the intimal-media of the aorta, and the percentage of area of lesion in the aorta, while plasma 6-keto-PGF1 alpha showed significantly negative correlation with the above data. TXB2/6-keto-PGF1 alpha was found to be positively correlated with the percentage of lesion area of the aorta. It was shown that Ca2+ metabolism plays an important role in thromboxane, prostaglandin, and LPO metabolism. In conclusion, the inhibition of LPO production and regulation of TXA2-PGI2 balance may be one of the main mechanisms of the antiatherogenic effects of calcium antagonists and PLP.
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PMID:[The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall. on atherogenesis in rabbits]. 187 9

We investigated the effects of neuropeptide Y on the prostacyclin production of cultured porcine aortic endothelial cells by measuring the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, by radioimmunoassay. Neuropeptide Y induced dose- and time-dependent stimulation of prostacyclin production by cultured porcine aortic endothelial cells. The lowest stimulatory concentration of neuropeptide Y was 10(-8) M and maximal response, a 2.8 fold rise, was obtained with 10(-6) M. The stimulation lasted at least 24 h. The effect was associated with the stimulation of arachidonic acid release. Our data suggest that neuropeptide Y may inhibit the development of atherosclerosis by stimulating prostacyclin synthesis.
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PMID:Neuropeptide Y stimulates prostacyclin production in porcine vascular endothelial cells. 188 60

Alterations in the synthesis of thromboxane A2 (TxA2) and prostacyclin have been implicated in the development of atherosclerosis. We measured the amounts of the degradation products of these substances, TxB2 and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), respectively, as well as PGE2, that were synthesized by slices and the luminal surfaces of aortas from rabbits fed either a control diet or a diet supplemented with cholesterol and peanut oil. For these studies, we developed conditions that were designed to minimize the autoinactivation of cyclooxygenase during removal and preparation of the tissue. Pretreatment of aortas with a medium containing ibuprofen and EDTA resulted in an approximately twofold increase in 6-oxo-PGF1 alpha production upon subsequent incubation. Despite the increased lipid peroxidation associated with atherosclerotic lesions, we observed no changes in either aortic 6-oxo-PGF1 alpha production or in the levels of its major urinary metabolite, 2,3-dinor-6-oxo-PGF1 alpha, after as long as 15 weeks of dietary supplementation with cholesterol and peanut oil. Similarly, synthesis of PGE2 by aortic slices and the aortic lumen was the same in cholesterol-fed and control rabbits. In contrast to aortic 6-oxo-PGF1 alpha and PGE2 synthesis, there was a dramatic 10-fold increase in TxB2 released from slices of thoracic aorta after 15 weeks on the atherogenic diet. This was much greater than the approximately twofold increase in the synthesis of TxB2 by the luminal surface of the thoracic aorta, suggesting that the primary site of TxB2 synthesis in the aorta is in the inner part of the blood vessel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis of prostaglandins and thromboxane B2 by cholesterol-fed rabbits. 190 62

Atherosclerosis was induced in male rabbits by administration of a 2% cholesterol diet for up to 18 weeks. The animals were assessed for aortic microsomal prostanoid synthesis, morphologic assessment and serum cholesterol levels. Serum levels of cholesterol increased from control values of 84 +/- 9 ng/dl to 1632 +/- 227 ng/dl at 2 weeks (20-fold increase), and 4859 +/- 829 ng/dl at 9 weeks (57-fold increase). Aortic microsomal prostacyclin synthesis fell significantly at 2 weeks of cholesterol feeding which predated the morphologic appearance of atherosclerotic plaque in the 7 week group. Aortic microsomal PGI2 synthesis significantly increased by 7 weeks and did not fall until the 18 week group when a highly significant increase in aortic plaque developed. These findings suggest a triphasic response of aortic PGI2 synthesis with the development of early atherosclerosis. Phase one is a fall in aortic PGI2 synthesis which predates the appearance of plaque. In phase 2, a significant rise in aortic PGI2 with the appearance of plaque could represent compensation of aortic endothelium to prevent further plaque development. In phase 3, decreased aortic PGI2 could indicate replacement of normal endothelium by atherosclerotic plaque.
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PMID:Triphasic response of prostacyclin production in rabbit thoracic aorta in early atherosclerosis. 194 59

The examination of 194 patients with coronary heart disease concurrent with clinical manifestations of angina pectoris established that the development of coronary atherosclerosis was accompanied by suppressed prostacyclin (PGI2) synthesis and increased thromboxane A2 (TxA2) leukotriene (LT) synthesis. The activation of synthesis of the vasoconstrictor and proaggregate TxA2 depended on the severity of clinical signs of angina pectoris. The imbalance of PGI2 to- TxA2 metabolite ratios was associated with dyslipidemias and the extent of coronary atherosclerosis. Bicycle ergometry testing resulted in prostanoid imbalance. The determination of the dynamics of prostanoids was used to check the efficiency of antianginal therapy. The concomitant application of inhibitors of thromboxane synthetase and LT synthesis was recommended for secondary prevention of thrombotic complications in patients with coronary atherosclerosis.
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PMID:[Pathogenetic and therapeutic significance of the angioprotective systems in patients with coronary arteriosclerosis]. 196 41

Cholesterol in the diet can readily autoxidize and be absorbed and transported in plasma lipoproteins. Cholesterol oxides can also be endogenously produced in tissues via free-radical-induced reactions. Some cholesterol oxides, notably cholestane-3 beta, 5 alpha, 6 beta-triol and 25-hydroxycholesterol, have been shown to cause injury to vascular endothelial and smooth muscle cells, to alter LDL receptor function, to enhance cholesteryl ester accumulation, to inhibit prostacyclin production, and to induce experimental atherosclerosis alone or in combination with cholesterol. An epidemiological study examining relationships between atherosclerosis and plasma levels of cholesterol oxides as independent risk factors may provide additional insights regarding the roles of cholesterol oxides in atherogenesis.
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PMID:Angiotoxicity and atherogenicity of cholesterol oxides. 202 60

Children whose parents had early coronary heart disease were investigated. In order to assess high-risk parameters serum total cholesterol (TC), total triglyceride (TT), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), lipid peroxide (LP), prostacyclin (PGI2), thromboxane (TX) levels, and the distribution of the complement 3 (C3), protein phenotypes were measured. Compared to a group of control children, the offspring of high-risk subjects had increased LDLC, LP, TC, and TX levels, a higher incidence of fast-slow heterozygotes, and decreased HDLC and PGI2 levels. The measurement of serum PGI2, TX levels and the distribution of C3 protein phenotypes may give further information about the true risk of atherosclerosis.
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PMID:Potential markers of the atherosclerotic process in high-risk children. 204 90

In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation.
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PMID:Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. 204 72


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