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)

Hypercholesterolemia is associated with more rapid development of atherosclerosis, and hypertension is frequently associated with abnormal vascular function. Therefore, to investigate the role of hypercholesterolemia and hypertension on vascular function, we studied three groups of male rats (aged 6 wk): normotensive Wistar-Kyoto rats (WKY) as a control group and spontaneously hypertensive rats (SHR) receiving either standard diet (SD; SHR-SD) or high-cholesterol (1%) diet (ChD; SHR-ChD). Vascular reactivity was tested on isolated aortic rings at 4 wk and at 3 and 6 mo of diet. At 3 mo, endothelium-dependent relaxation to acetylcholine (ACh) and ADP was significantly reduced in SHR-ChD but not in SHR-SD compared with WKY. At 6 mo, relaxations to ACh were further impaired in both SHR groups compared with WKY. Endothelium-independent vasodilation to nitroglycerin (NTG) was not different in the three groups of animals throughout 6 mo of diet. In additional experiments, we evaluated vascular reactivity in rats fed with ChD enriched with an excess of vitamin D [atherogenic diet (AD)] capable of producing vascular atherosclerotic lesions. In particular, we studied three additional groups of WKY and SHR rats fed with SD, AD, or AD plus a nonhypotensive dose of the calcium antagonist nitrendipine (Nit). Vasodilation to ACh and ADP was significantly blunted in WKY-AD compared with WKY-SD, whereas it was partially improved in WKY-Nit. There were no differences in endothelium-independent relaxation to NTG in the three WKY groups. In contrast, SHR-AD showed a marked reduction of endothelium-dependent and -independent vasodilation, but only endothelium-dependent vasodilation was preserved by addition of Nit to the diet. These data suggest that the development of vascular dysfunction in rat genetic hypertension is accelerated by ChD, in absence of detectable vascular lesions. Our study also shows that AD alters both vascular smooth muscle and endothelium-dependent relaxation. Low doses of Nit partially preserve endothelium-dependent vasodilation but do not affect the impairment of smooth muscle function in these rats.
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PMID:Effects of high-cholesterol and atherogenic diets on vascular relaxation in spontaneously hypertensive rats. 927 80

Sterol 27-hydroxylase is important for the degradation of the steroid side chain in conversion of cholesterol into bile acids and has been ascribed a regulatory role in cholesterol homeostasis. Its deficiency causes the autosomal recessive disease cerebrotendinous xanthomatosis (CTX), characterized by progressive dementia, xanthomatosis, and accelerated atherosclerosis. Mice with a disrupted cyp27 (cyp27(-/-)) had normal plasma levels of cholesterol, retinol, tocopherol, and 1,25-dihydroxyvitamin D. Excretion of fecal bile acids was decreased (<20% of normal), and formation of bile acids from tritium-labeled 7alpha-hydroxycholesterol was less than 15% of normal. Compensatory up-regulation of hepatic cholesterol 7alpha-hydroxylase and hydroxymethylglutaryl-CoA reductase (9- and 2-3-fold increases in mRNA levels, respectively) was found. No CTX-related pathological abnormalities were observed. In CTX, there is an increased formation of 25-hydroxylated bile alcohols and cholestanol. In bile and feces of the cyp27(-/-) mice only traces of bile alcohols were found, and there was no cholestanol accumulation. It is evident that sterol 27-hydroxylase is more important for bile acid synthesis in mice than in humans. The results do not support the contention that 27-hydroxylated steroids are critical for maintenance of cholesterol homeostasis or levels of vitamin D metabolites in the circulation.
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PMID:Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene. 961 81

The optimal surgical procedure for severe renal secondary hyperparathyroidism (sHPT) is still a point of controversy. Total parathyroidectomy (PTX) without auto-transplantation was abandoned for fear of an adynamic bone condition; however, in the case of autotransplantation recurrent sHPT is frequent and promotes atherosclerosis. We studied 11 hemodialysis patients (age 59+/-12 years) on dialysis for 18 (12-30) years in whom total PTX was performed due to severe sHPT (group I; intact PTH: 1,240+/-230 pg/ml), and 5 patients (age 55+/-10 years) without renal insufficiency who inadvertently received total PTX during thyroid surgery (group II). After total PTX (group I, 26+/-18 [9-59] months; group II, 252+/-188 [22 480] months) both groups showed no measurable intact PTH levels. Calcium homeostasis was maintained by oral substitution with calcium (group I, calcium dialysate of 2.0 mmol/l), vitamin D and calcitriol (serum parameters in groups I and II: calcium 2.4 and 2.2 mmol/l; phosphate 1.8 and 1.1 mmol/l; 25(OH)-vitamin D(3) 21 and 34 ng/ml; 1,25(OH)(2)-vitamin D(3) 32 and 41 pg/ml, respectively). In group I, after total PTX there was a rapid and sustained improvement in bone pain with markedly enhanced physical activity and endurance. High turnover osteopathy markedly improved as indicated by declining levels of native osteocalcin (90+/-17 vs. 26+/-18 ng/ml), bone alkaline phosphatase (74+/-12 vs. 12+/-6 ng/ml), and carboxyterminal cross-linked telopeptide of type-I collagen (65+/-16 vs. 40+/-21 ng/ml) but increasing levels of carboxyterminal propeptide of type-I procollagen (120+/-36 vs. 148+/-41 ng/ml). Recalcification of bone was excellent as demonstrated by X-ray and confirmed by bone histology. Itching extravascular calcific deposits and calcifications of blood vessel and cardiac valves immediately stopped after total PTX. Moreover, 6 sHPT patients suffered from severe atherosclerotic lesions such as thoracic aortic aneurysm (n = 3) or abdominal aortic aneurysm (n = 3) which showed size progression before but not after total PTX when annually controlled by ultrasonography. In group II, even long after total PTX, there was no clinical, radiological, histological or biochemical evidence for low turnover osteopathy. In conclusion, our data indicate that substitution with vitamin D(3) metabolites and calcium can prevent deleterious bone effects of hypoparathyroidism in hemodialysis patients and in patients with normal kidney function and may compensate for the missing PTH action. Over this, a better survival rate is expected as a consequence of the beneficial effect of total PTX on the progression of atherosclerotic lesions. We suggest reconsideration of total PTX without autotransplantation in dialysis patients with severe sHPT who are not eligible for renal transplantation.
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PMID:Long-term results of total parathyroidectomy without autotransplantation in patients with and without renal failure. 1043 1

We have shown earlier that sitostanol ester margarine lowers serum cholesterol by inhibiting cholesterol absorption so that, theoretically, there could be interference with the absorption of fat-soluble vitamins. Accordingly, we investigated whether sitostanol ester margarine affects the serum levels of vitamin D, retinol, alpha-tocopherol and alpha- and beta-carotenes during 1-year treatment in 102 subjects and 49 controls with moderate hypercholesterolemia. The vitamins were assayed at baseline on home diet, on margarine alone, after 1 year's consumption of sitostanol ester margarine and after an additional 2 months on home diet. In the sitostanol group, serum plant sterols, indicators of cholesterol absorption efficiency, were reduced up to -38% in relation to controls from home diet (P < 0.01) indicating that cholesterol absorption was markedly reduced. Vitamin D and retinol concentrations and the ratio of alpha-tocopherol to cholesterol were unchanged by sitostanol ester. Serum beta-carotenes and alpha-carotene concentration but not proportion were reduced in the sitostanol group from baseline and in relation to controls (P < 0.01). Retinol and vitamin D were unassociated with serum cholesterol, plant sterols or other vitamins, whereas alpha-tocopherol and carotenes were significantly associated with serum plant sterols suggesting that the higher cholesterol absorption efficiency, the higher the alpha-tocopherol and carotene levels in serum. We conclude that sitostanol ester did not affect vitamin D and retinol concentrations and alpha-tocopherol/cholesterol proportion, but reduced serum beta-carotene levels. Alpha-tocopherol and carotenes, but not vitamin D and retinol, were related to serum cholesterol and cholesterol absorption.
Atherosclerosis 1999 Aug
PMID:Retinol, vitamin D, carotenes and alpha-tocopherol in serum of a moderately hypercholesterolemic population consuming sitostanol ester margarine. 1048 54

Vascular calcification is an active and modifiable process involved in many disease entities, including atherosclerosis, cardiac valve disease and calcific uremic arteriolopathy. It occurs with distinct characteristics at different sites in the vessel wall. The mechanism by which calcification is induced remains uncertain; the roles of bone matrix and extracellular matrix proteins, estrogen and vitamin D are being further defined in animal models and clinical trials. Some risk factors for calcific uremic arteriolopathy and cardiac valve calcification, both disproportionately affecting chronic hemodialysis patients, have been identified in observational studies.
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PMID:Vascular calcification. 1049 39

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors that belong to the steroid receptor superfamily. This family of PPARs includes PPARalpha, PPARdelta, PPARgamma1, and PPARgamma2. These PPARs are related to the T3 and vitamin D(3) receptors and bind to a hexameric direct repeat as a heterodimeric complex with retinoid receptor Xalpha. PPARs regulate the expression of a wide array of genes that encode proteins involved in lipid metabolism, energy balance, eicosanoid signaling, cell differentiation, and tumorigenesis. A unique feature of these steroid-like receptors is that the physiologic ligands for PPARs appear to be fatty acids from the n-6 and n-3 families of fatty acids and their respective eicosanoid products. This review describes the characteristics, regulation, and gene targets for PPARs and relates their effects on gene expression to physiologic outcomes that affect lipid and glucose metabolism, thermogenesis, atherosclerosis, and cell differentiation.
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PMID:Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors. 1050 27

Two types of haematogenous osteomyelitis that are seen in the elderly are vertebral and long bone osteomyelitis. Osteomyelitis secondary to contiguous foci of infection can occur in older adults without vascular insufficiency (secondary to pressure ulcers) or with vascular insufficiency due to diabetes mellitus or peripheral vascular disease from atherosclerosis. Most cases of osteomyelitis can be reasonably treated with adequate drainage, thorough debridement, obliteration of dead space, wound protection, and antimicrobial therapy. Patients are initially given a broad spectrum antimicrobial that is changed to specific antimicrobial therapy based on meticulous bone cultures taken at debridement surgery or from deep bone biopsies. Surgical management is often required in the treatment of osteomyelitis and includes adequate drainage, extensive debridement of all necrotic tissue, obliteration of dead spaces, stabilisation, adequate soft tissue coverage, and restoration of an effective blood supply. Bone repair and bone mineral density may be significantly retarded and may be corrected by eliminating risk factors, supplementing the diet with calcium, bisphosphonates, and/or vitamin D, and treating with testosterone and/or estrogen when deficient. Sodium fluoride treatment and anabolic steroids may be used as alternatives. Septic arthritis is a medical emergency, and prompt recognition and rapid and aggressive treatment are critical to ensuring a good prognosis. The treatment of septic arthritis includes appropriate antimicrobial therapy and joint drainage. Adverse effects of prescribed antibacterials occur more often in the elderly patient than in young adults. The physician can help to minimise the incidence of adverse effects and improve outcomes by being aware of the principles of clinical pharmacology, the characteristics of specific drugs, and the special physical, psychological and social needs of older patients.
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PMID:Bone and joint infections in the elderly: practical treatment guidelines. 1073 65

Excessive intake of saturated fatty acids and/or linoleic acid favors the induction of an array of lipid mediators and cytokines enhancing inflammatory responses. Conversely, dietary supplementation with (n-3) fatty acids or vitamin D ameliorates inflammation and autoimmune diseases. Although it was well accepted that conjugated linoleic acid (CLA) prevented diseases with a common inflammatory pathogenesis (i.e., cancer and atherosclerosis), no studies were available on the roles of CLA in mucosal inflammation. The present study was designed to investigate the anti-inflammatory actions and molecular mechanisms underlying the regulation of colonic health by CLA. We hypothesized that colonic inflammation can be ameliorated by dietary CLA supplementation. To test this hypothesis, inflammation of the colonic mucosa was triggered by challenging pigs fed either soybean oil-supplemented or CLA-supplemented diets with an enteric bacterial pathogen (i.e., Brachyspira hyodysenteriae). Immunoregulatory cytokines and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression were assayed in colonic lymph nodes and colon of pigs. Colonic mucosal lesions and lymphocyte subset distribution were evaluated by histology and immunohistochemistry. Supplementation of CLA in the diet before the induction of colitis decreased mucosal damage; maintained cytokine profiles (i.e., interferon-gamma and interleukin-10) and lymphocyte subset distributions (i.e., CD4+ and CD8+), resembling those of noninfected pigs; enhanced colonic expression of PPAR-gamma; and attenuated growth failure. Therefore, CLA fed preventively before the onset of enteric disease attenuated inflammatory lesion development and growth failure.
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PMID:Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. 1209 86

The steroid hormone 1alpha,25-dihydroxyvitamin D3 [1alpha, 25-(OH)2D3] promotes vascular smooth muscle cell (VSMC) growth and calcification, but the precise mechanism by which 1alpha, 25-(OH)2D3 regulates VSMC migration is unknown. In rat aortic SMCs, we found that 1alpha, 25-(OH)2D3 (0.1 to 100 nmol/L) induced a dose-dependent increase in VSMC migration. This response required the activation of phosphatidylinositol 3-kinase (PI3 kinase) because 1alpha, 25-(OH)2D3-induced migration was completely abolished by the PI3 kinase inhibitors, LY294002 (10 micromol/L) or wortmannin (30 nmol/L). Furthermore, the RNA polymerase inhibitor, 5,6-dichlorobenzimidazole riboside (50 micromol/L), did not affect 1alpha, 25-(OH)2D3-induced VSMC migration, suggesting that gene transcription is not involved in this rapid response. Using analogs of 1alpha, 25-(OH)2D3, which have been characterized for their abilities to induce either transcriptional or nontranscriptional responses of 1alpha, 25-(OH)2D3, we found that 1alpha,25-dihydroxylumisterol, which is a potent agonist of the rapid, nongenomic responses, was equipotent with 1alpha, 25-(OH)2D3 in inducing PI3 kinase activity and VSMC migration. Moreover, 1beta, 25-(OH)2D3, which specifically antagonizes the nongenomic actions of 1alpha, 25-(OH)2D3, abolished 1alpha, 25-(OH)2D3-induced PI3 kinase activity and VSMC migration, whereas the inhibitor of the genomic actions of vitamin D, (23S)-25-dehydro-1alpha-OH-D3-26,23-lactone, did not affect these responses. These results indicate that 1alpha, 25-(OH)2D3 induces VSMC migration independent of gene transcription via PI3 kinase pathway, and suggest a possible mechanism by which 1alpha, 25-(OH)2D3 may contribute to neointima formation in atherosclerosis and vascular remodeling.
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PMID:1alpha,25-dihydroxyvitamin D3 induces vascular smooth muscle cell migration via activation of phosphatidylinositol 3-kinase. 1211 17

Osteoporosis features include reduction of bone mass and increased predisposition to fractures. Osteoporosis is considered as one of frequent diseases developing in menopausal women and old men. The values of peak bone mass are the determinant of osteoporosis development. It is estimated that the peak bone mass is reached at the age between 16 and 30 years. (NIH Consensus, 2001). Insufficient intake of calcium and vitamin D in diet, with reduced sun exposure, low physical activity, low body weight are well documented risk factors for this disease in human. For that reason, in osteoporosis prevention it should be tried to ensure adequate supply of calcium in diet from early life, with adequate supply of vitamin D, as factors determining adequate mineralization of osseous tissue. The study was carried out for assessing changes of the levels of calcium and 25-OH cholecalciferol in serum replacing butter in usual diet with margarine enriched with vitamin D. After a period of diet stabilization the study group received first diet with butter, followed by diet with margarine in place of butter. Throughout the whole experiment the diet contained unchanged amounts of dairy products as a source of alimentary calcium. In the experiment 41 young healthy men aged 22.6 +/- 1.2 years participated. Every subject consumed in a period of 4 weeks 30 g of butter daily, and during the following 4 weeks margarine 30 g daily. Substitution of margarine for butter in usual diet raised 25-OH cholecalciferol level in serum by 5.56 ng/ml, that is 32.4% (p < 0.001), with consequent 0.12 mg (5%) rise of serum calcium level (p < 0.05). The intake of calcium with diet from dairy products was unchanged throughout the experiment 576-581 mg daily, that is 72% of the recommended intake. The obtained results suggest that independently of the amount of vitamin D intake with food and calcium with diet substitution of margarine enriched with vitamin D for butter was beneficial raising serum vitamin D level, and at the same time increasing calcium absorption from food. It can be accepted that the obtained results could support the opinion on beneficial effects of the consumption of high-quality margarine in daily diet as prevention of the development not only of atherosclerosis but also osteoporosis.
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PMID:[Increased serum levels of vitamin D and calcium in young men after replacement of butter with soft margarine in usual diet]. 1264 39


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