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)

Cellular components of the bronchovascular barrier have been studied in human lungs obtained after death of some patients with acute and chronic lung inflammatory diseases, hypertonic disease, atherosclerosis and chronic glomerulonephritis. Certain oxidative-reductive and hydrolytic enzymes, including NAD-, NADP- diaphorases, lactic dehydrogenase, acid and alkaline monophosphoesterase, ATP-ase, adenylate cyclase and nonspecific esterase were evaluated quantitatively after the histochemical processing of the specimens for the above reactions. Correlation analysis was performed for the bronchial epithelium, endotheliocytes, lymphocytes, plasma and mast cells, as well as macrophages and polymorphonuclear leucocytes. The results showed that there was a significant shift in some of the measured enzymic activities. Moreover, the correlations between different quantitative data were noted and these correlations changed with age. The increase in "rigidity" of the correlations in the elements of the bronchovascular barrier has been demonstrated during the process of ageing.
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PMID:Functional morphology of the bronchovascular barrier of the human lungs during various age periods. 214 10

Although the use of lipids should be individualized, certain generalizations are appropriate. 1. Lipid infusion should be limited in the fulminately septic patient to 10% of total calories in an effort to reduce immunosuppression. 2. The stressed, nonseptic patient with difficulties in ventilator weaning or TPN-induced hepatic dysfunction may reap benefit from a reduction in dextrose calories and the provision of daily lipids. 3. Patients with severe autoimmune disease have had mild amelioration of symptoms with PUFA supplementation. The relative benefits of omega-6 vs omega-3 continue to be examined. 4. Dietary immunomodulation in transplant and burns remains an area of active investigation. 5. Patients with fat-free TPN show transient declines in serum lipids. The development of a "fat-solubilizer" remains in the experimental realm. 6. The provision of fish oil, high in W-3 EPA, has shown promise in atherosclerosis and immunomodulation. The changes in the relative amounts of each prostaglandin class depend on precursor prevalence.
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PMID:Practicalities of lipids: ICU patient, autoimmune disease, and vascular disease. 223 6

In healthy persons, glucose homeostasis maintains blood glucose levels between 70 and 130 mg/dl despite perturbations by meals, fasting, and exercise. Long-term follow-up of diabetic patients has suggested that "good control" of blood sugar levels minimizes the long-term complications of diabetes, such as retinopathy, nephropathy, and atherosclerosis. It now seems likely the products of insulin-independent metabolic pathways in epithelial and endothelial cells leading to polyol formation and protein glycosylation may be factors in the genesis of retinopathy, neuropathy, nephropathy, and premature atherosclerosis of diabetic patients. Dietary complex carbohydrates of various type, including those rich in dietary fiber, which are the cell walls of fruits, vegetables, and cereals, may slow the rate of absorption of glucose from those diets and contribute to a lowering of the postprandial glucose peak. Glycemic responses to various foods compared to glucose have been studied and show a large variation, which is dependent upon gastric emptying, overall effects on rate of hydrolysis and absorption of glucose from food mixtures. Dietary sucrose seems to cause a degree of insulin resistance. The active part of the disaccharide is fructose, which does not elicit an acute insulin response, but appears indirectly to increase insulin levels in both animals and man. Sucrose in animals appears to promote obesity more than glucose because of its lack of stimulation of thermogenesis. Xylitol has been used as a sweetener and as a sugar substitute in total parenteral nutrition. It is a paradox that the most physiological of sugars (glucose) can be a menace at high concentrations. The use of nonphysiological sugars or their derivatives in diabetics and patients with special needs, such as TPN, requires much more investigation to develop a sound rationale in nutrition management.
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PMID:Monosaccharides in health and disease. 352 17

Quantitative determination of the nucleotides AMP, ADP, ATP, GTP, NAD, NADP, 2,3-DPG and the free amino acids Lys, His, Gly, Ala, Val, Met, Phe, Tyr, Pro, Thr, Ser, Glu, Asp in erythrocytes was carried out in early and late stages of myocardial infarction. It was found that in erythrocytes, in the early stage of myocardial infarction, the concentrations of AMP, NADP and 2,3-DPG increased, whereas those of ADP, ATP, GTP and NAD decreased. In the third week of the disease the concentrations of AMP, ADP, NADP, and especially 2,3-DPG remained high, while those of ATP and GTP shifted towards the control. The concentrations of His, Gly, Ala, Val, Met, Phe, Thr and Glu increased, while those of Tyr, Ser and Asp decreased in the first stage of myocardial infarction. At the later stage of the illness (21 days) the concentrations of free amino acids returned to normal.
Atherosclerosis
PMID:Myocardial infarction. Changes in the concentrations of high-energy compounds and free amino acids in erythrocytes. 733 15

Study of the key mechanisms, metabolism regulators, showed that in the blood of patients with atherosclerosis the NAD/NAD . N ratio decreases by 59.8% and the NAD+ concentration by 44%, while the NAD . N content increases by 56.7%. In the nicotinamide adenine dinucleotide system there is a general tendency tomards accumulation:the concentration of NADP+ grows by 218.6% and that of NADP . N by 12.9%. A marked increase in the content of incompletely oxidized products is determined: lactic acid by 37.4%, alpha-glycerophosphate by 49.8%, dihydroxyacetone phosphate by 155%, oxaloacetate by 131% in the presence of lactate dehydrogenase and malate dehydrogenase activation. The detected changes are evidence of tissue energy debt in atherosclerosis, they reflect the character of metabolic acidosis formation and point to the presence of conditions for intensified liposynthesis.
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PMID:[Content of nicotinamide coenzymes, metabolites and the NAD-dependent dehydrogenase activity in the blood in arteriosclerosis]. 737 12

When experimental animals are kept on an atherogenic diet the NADP.H-dependent phospholipid deoxygenase in the membranes of the hepatic endoplasmic reticulum is activated and the degree of membrane oxidation is increased. "Peroxide" modification of microsomal membranes is attended by changes in their conformation and as a consequence, changes in the activity of membrane-bound enzymes. Proceeding from the fact that the synthesis of the components and the assembly of the supramolecular lipoprotein structure as well as cholesterol catabolism are accomplished by the enzyme systems localized in the hepatic microsomes, the role of peroxidation of the microsomal lipids in the pathogenesis of atherosclerosis is discussed.
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PMID:[Lipid peroxides and atherosclerosis. Hypothesis: the role of cholesterol and free-radical lipid peroxidation in altering cell membrane properties in hypercholesterolemia and atherosclerosis]. 741 95

Cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis, has been implicated in atherosclerosis and gallstone disease. The aim of this study was to check if the use of hydroxypropyl-beta-cyclodextrin (HPBCD), a vehicle for solubilizing cholesterol, augmented the rate of 7 alpha-hydroxycholesterol formation in hamster liver microsomes compared to classical assays in which labeled cholesterol was delivered in Tween 80. We observed that [14C]cholesterol carried by HPBCD enhanced the sensitivity of the assay tenfold. However, linearity of 7 alpha-hydroxycholesterol formation with time was short because of the rapid transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one and 7 alpha,12 alpha-dihydroxy-cholesten-3-one when NADPH alone was present in the incubation medium. In order to avoid the transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one, which is essentially NAD(+)-dependent, but is also NADP(+)-dependent, NADPH (1 mmol/l) plus an NADPH-regenerating system must be present in the medium. In this improved assay, the optimal pH was 7.4 and the apparent Km for control and cholestyramine-fed hamsters had a similar value of 315 mumol/l; linearity in the formation of 7 alpha-hydroxycholesterol was also apparent after a relatively short time period (10 min), but with a markedly greater slope of the curve. With a short incubation time (6 min), microsomes from livers of hamsters (five and nine weeks old) that were fed with a commercial ground diet yielded rates of 7 alpha-hydroxycholesterol formation of 115 +/- 10 and 150 +/- 16 pmol/min.mg protein, respectively, whereas microsomes from hamsters fed with a lithogenic sucrose-rich diet (five weeks old) yielded rates of 7 alpha-hydroxycholesterol formation of 77 +/- 7 pmol/min.mg protein, which were significantly lower (-33%) than those of corresponding control hamsters. This improved cholesterol 7 alpha-hydroxylase assay is very sensitive, simple and rapid, and does not necessitate sophisticated equipment. It can be particularly useful for determining cholesterol 7 alpha-hydroxylase activity in liver biopsies from dyslipidemic or lithiasic patients.
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PMID:Improved assay of hepatic microsomal cholesterol 7 alpha-hydroxylase activity by the use of hydroxypropyl-beta-cyclodextrin and an NADPH-regenerating system. 952 78

Clinical and experimental evidence suggests that the pathways by which hypertension and dyslipidemia lead to vascular disease may overlap and that angiotensin II (Ang II) is involved in restructuring of the arterial wall in both atherosclerosis and hypertension. Ang II represents a potent proinflammatory agent promoting recruitment of monocytes into the vascular intima. Ang II also indirectly facilitates transformation of macrophages and smooth muscle cells into foam cells by promoting superoxide radical formation (via NADP/NADPH oxidase stimulation). The oxidative stress produced by Ang II leads to enhanced low-density lipoprotein oxidation and degradation of nitric oxide, an important vascular protective molecule capable of retarding atherosclerosis progression. The importance of the renin-angiotensin system (RAS) in atherogenesis is highlighted by studies in animal models as well as human beings indicating that inhibition of angiotensin-converting enzyme or blockade of type 1 Ang II receptors retards the development of atherosclerotic lesions. In light of a causal and central role of Ang II in atherogenesis, blockade of the RAS represents an important therapeutic consideration in the prevention and treatment of atherosclerotic disease.
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PMID:Renin-angiotensin system as a therapeutic target in managing atherosclerosis. 1470 95

The renin-angiotensin system contributes to atherogenesis. Matrix metalloproteinases (MMP) are thought to participate in plaque destabilization through degradation of extracellular matrix. This study tested whether angiotensin II (ANG II) induces MMP in human vascular smooth muscle cells (SMC). ANG II induced expression of MMP-1, -3, and -9, but not of MMP-2 in SMC. The expression of MMP-1, a key enzyme for collagen degradation, was studied in detail. SMC stimulated with ANG II concentration-dependently released enzymatically active MMP-1. The ANG II type 1 receptor antagonists losartan and candesartan blocked ANG-II-induced MMP-1 release. Inhibition experiments with actinomycin D suggest ANG-II-induced MMP-1 mRNA regulation at the transcriptional level. Decoy oligodeoxynucleotides against nuclear factor-kappaB and activator protein 1 inhibited MMP-1 secretion, demonstrating participation of these transcription factors in MMP-1 transcription. Stimulation of MMP-1 by ANG II depended on cyclooxygenase 2. The antioxidants pyrrolidine dithiocarbamate and N-acetylcysteine, the flavin protein inhibitor diphenylene iodonium, and the NADP(H) oxidase inhibitor apocynin blocked MMP-1 release, suggesting a redox-sensitive mechanism involving NADP(H) oxidase. The reactive oxygen species (ROS) donor 2,3-dimethoxy-1,4-naphthoquinone induced MMP-1 secretion and enhanced ANG-II-stimulated MMP-1 expression. These findings indicate that ROS may increase their own production by activation of NADP(H) oxidase. The capability of ANG II to induce functionally active MMP in human SMC may contribute to the altered plaque composition seen in complicated stages of atherosclerosis.
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PMID:Angiotensin II stimulates matrix metalloproteinase secretion in human vascular smooth muscle cells via nuclear factor-kappaB and activator protein 1 in a redox-sensitive manner. 1610 92

Nitrate-based vasodilators (NBVs) are commonly used to treat multiple sequelae of atherosclerosis. A commonly used NBV, glyceryl trinitrate (GTN) is bioactivated by mitochondrial, class 2 aldehyde dehydrogenase (ALDH2). ALDH2 and other ALDHs are NAD(P)+-dependent enzymes critical to the detoxification of cytotoxic lipid-aldehydes elevated in atherosclerotic lesions, such as trans-4-hydroxy-2-nonenal (HNE). The GTN bioactivation step, however, inac-tivates ALDH2 and may alter the metabolism of these aldehydes. In this study, we tested the hypothesis that multiple ALDH enzymes are inhibited by different NBVs. ALDH2, ALDH3A, and ALDH5A were present in aorta with ALDH2 and ALDH3A localized to the smooth muscle layers. GTN (1 microM) inhibited ALDH2 activity (55 +/- 6% of control) and ablated ALDH3 activity. In contrast, isosorbide-2,5-dinitrate (ISDN, 1 microM) inhibited ALDH3 activity (1.1 +/- 0.4% of control) but did not inhibit ALDH2 activity even up to 50 microM ISDN. In homogenates of rat aorta, GTN (1 microM) inhibited the NAD+-dependent (41 +/- 5% of control) and NADP+-dependent (25 +/- 6% of control) detoxification of HNE. The inhibition of ALDH3A, but not ALDH2, could be prevented by the addition of dithiothreitol. These studies demonstrate that GTN and ISDN possess selectivity for ALDH inactivation with different mechanisms of inactivation.
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PMID:Nitrate-based vasodilators inhibit multiple vascular aldehyde dehydrogenases. 1624 77


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