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

Cardiovascular diseases and cancers constitute major public health problems in all industrialized countries, where they are the main causes of premature mortality. There is a large body of evidence suggesting that free-radical production can directly or indirectly play a major role in cellular processes implicated in atherosclerosis and carcinogenesis. Here we present mechanistic data and results of epidemiologic studies on the relationship between antioxidant vitamin intake or biochemical status and the risk of cancer and cardiovascular diseases. Most epidemiologic data obtained on this topic were based on an observational approach, i.e., ecologic, case-control, or prospective studies. All these studies indicate that a high dietary intake or high blood concentrations of antioxidant vitamins are associated with a reduced risk of cardiovascular diseases and cancer at several common sites. Although the results of these studies are convergent, they merely suggest a relationship at the population and individual level but do not affirm a causality link. Only intervention studies (randomized trials), by specifically changing antioxidant vitamin intake, can provide conclusive answers. The apparent discrepancies between the results of four recently published trials may be explained by the type of population (general or high-risk subjects), the differing doses of supplementation (nutritional levels or higher), the number of antioxidants tested (one, two, or more), and the type of administration (alone or in balanced association). It thus appears that a low risk of pathologies may be related to multiple nutrients consumed at nutritional doses and in combination. Optimal effects may be expected with a combination of nutrients at levels similar to those found in a healthy diet. A single antioxidant vitamin given at high doses in subjects with high risk of pathologies (smokers, asbestos-exposed subjects) may not have substantial benefits and could even have negative consequences.
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PMID:The potential role of antioxidant vitamins in preventing cardiovascular diseases and cancers. 964 92

Evidence continues to accumulate on the importance of neutrophils (PMNs) and phagocytes in the causation of tissue and endothelial injury that frequently accompanies the inflammatory response. Increased production of superoxide anions in combination with decreased endothelial antioxidant activity may contribute to the development of vascular disease including atherosclerosis, vasospasm, diabetic vascular complications, tissue damage in ischemia-reperfusion, and hypotension. Free radicals generated in the vascular wall may act directly on smooth muscle or interact with each other thus producing biologically active endogenous mediators. Derangement of macrophage function may occur in conditions characterized by protein malnutrition, thus leading to failure to develop a specific immunoresponse and to an increase in the production of oxygen intermediate radicals, which may cause tissue damage. A local inflammatory response followed by endothelial cell activation could also facilitate migration of immunocompetent cells into the parenchyma of grafted organs and stimulate dendritic cells in the graft. There is now convincing evidence that excessive and prolonged production of NO contributes to tissue damage in septicemia, ischemia/reperfusion injury, and other inflammatory conditions. There is also increasing evidence that the complement system plays an important role in tissue damage in association with phagocytes, e.g., in ischemia/reperfusion injury, carcinogenesis, and aging. It can therefore be surmised that phagocytic cells may act both as "friends" and as "foes" and that they are important mediators of tissue damage in a variety of conditions.
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PMID:Host tissue damage by phagocytes. 970 69

Reactive oxygen species are involved in a diversity of biological phenomena such as inflammation, carcinogenesis, aging, and atherosclerosis. We and other investigators have shown that the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress, is increased in either the urine or the mononuclear cells of the blood of type 2 diabetic patients. However, the association between type 2 diabetes and oxidative stress in the pancreatic beta-cells has not been previously described. We measured the levels of 8-OHdG and 4-hydroxy-2-nonenal (HNE)-modified proteins in the pancreatic beta-cells of GK rats, a model of nonobese type 2 diabetes. Quantitative immunohistochemical analyses with specific antibodies revealed higher levels of 8-OHdG and HNE-modified proteins in the pancreatic beta-cells of GK rats than in the control Wistar rats, with the levels increasing proportionally with age and fibrosis of the pancreatic islets. We further investigated whether the levels of 8-OHdG and HNE-modified proteins would be modified in the pancreatic beta-cells of GK rats fed with 30% sucrose solution or 50 ppm of voglibose (alpha-glucosidase inhibitor). In the GK rats, the levels of 8-OHdG and HNE-modified proteins, as well as islet fibrosis, were increased by sucrose treatment but reduced by voglibose treatment. These results indicate that the pancreatic beta-cells of GK rats are oxidatively stressed, and that chronic hyperglycemia might be responsible for the oxidative stress observed in the pancreatic beta-cells.
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PMID:Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. 1010 16

Insulin-like growth factor I (IGF-I) is a ubiquitous endocrine, paracrine and autocrine polypeptide, which influences cell proliferation and differentiation in many tissues. Classically, IGF-I has been tied to growth hormone (GH) and has often been considered a surrogate marker of overall GH status. The advent of recombinant technology has made possible studies of GH and IGF-I for the treatment of chronic diseases (such as diabetes mellitus, osteoporosis and muscle atrophy) as well as to forestall the aging process. Examples of currently active areas of research include efforts to define the involvement of IGF-I physiology in bone remodeling, atherosclerosis and neoplasia. Recent epidemiological evidence suggests that individuals with IGF-I levels in the 'high normal' range have increased risk of common cancers relative to individuals with levels in the 'low normal' range. These findings have focused renewed attention on the genetic and non-genetic determinants of serum IGF-I levels. It is unlikely that the serum IGF-I level itself is related directly to risk of neoplasia, but it may serve as a surrogate for a variable that is important in epithelial cell carcinogenesis, such as rate of epithelial cell proliferation. We review relatively new data suggesting that adult serum IGF-I levels are under the control of heritable factors apart from GH. Such factors may influence tissue expression of IGF-I as well as serum IGF-I levels, and influence a number of clinically important outcomes, including bone density and risk of neoplasia. The concept that there is little physiological importance in the heterogeneity between individuals regarding IGF-I levels within the broad 'normal' range may require re-assessment.
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PMID:Circulating IGF-I: New Perspectives for a New Century. 1032 7

The peroxisome proliferator-activated receptor gamma (PPARgamma) quickly evolved over the last decade from a new orphan receptor to one of the best characterized nuclear receptors. This fast pace in PPARgamma research was triggered by two main discoveries. Firstly, that PPARgamma was shown to have a key role in adipogenesis and be a master controller of the "thrifty gene response" leading to efficient energy storage. Secondly, the discovery that its synthetic ligands, the thiazolidinediones, are promising insulin sensitizing drugs, which are currently being developed for the treatment of Type II (non-insulin-dependent) diabetes mellitus. More recently this nuclear receptor emerged from a role limited to metabolism (diabetes and obesity) to a power player in general transcriptional control of numerous cellular processes, with implications in cell cycle control, carcinogenesis, inflammation, atherosclerosis and immunomodulation. This widened role of PPARgamma will certainly initiate a new flurry of research, which will not only refine our current often partial knowledge of PPARgamma but more importantly also establish that this receptor has a definite role as a primary link adapting cellular, tissue and whole body homeostasis to energy stores.
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PMID:PPARgamma, the ultimate thrifty gene. 1044 13

Flavonoids containing phenol B rings, e.g. naringenin, naringin, hesperetin and apigenin, formed prooxidant metabolites that oxidised NADH upon oxidation by peroxidase/H2O2. Extensive oxygen uptake occurred which was proportional to the NADH oxidised and was increased up to twofold by superoxide dismutase. Only catalytic amounts of flavonoids and H2O2 were required indicating a redox cycling mechanism that activates oxygen and generates H2O2. NADH also prevented the oxidative destruction of flavonoids by peroxidase/H2O2 until the NADH was depleted. These results suggest that prooxidant phenoxyl radicals formed by these flavonoids cooxidise NADH to form NAD radicals which then activated oxygen. Similar oxygen activation mechanisms by other phenoxyl radicals have been implicated in the initiation of atherosclerosis and carcinogenesis by xenobiotic phenolic metabolites. This is the first time that a group of flavonoids have been identified as prooxidants independent of transition metal catalysed autoxidation reactions.
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PMID:Oxygen activation during peroxidase catalysed metabolism of flavones or flavanones. 1047 12

2-Amino-1-methyl-phenylimidazo[4,5b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine produced in cooked meat and fish, is known to be a carcinogen for rats and mice. This study provides the first evidence for hypertriglyceridemia in rats exposed to PhIP, suggesting its potential risk to induce not only carcinogenesis, but also atherosclerosis, and highlighting the potential importance of PhIP for humans.
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PMID:Hypertriglyceridemia in rats induced by consumption of a food-derived carcinogen, 2-amino-1-methyl-phenylimidazo[4,5b]pyridine (PhIP). 1054 Jul 52

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that controls the expression of a large array of genes involved in adipocyte differentiation, lipid storage and insulin sensitization. PPARgamma is bound and activated by prostaglandin J2 and fatty acid derivatives, which are its natural ligands. In addition, thiazolidinediones and nonsteroidal anti-inflammatory drugs are synthetic ligands and agonists of this receptor. Several studies have recently shown that this nuclear receptor has a role expanding beyond metabolism (diabetes and obesity) with functions in cell cycle control, carcinogenesis, inflammation and atherosclerosis. This review addresses the role of PPARgamma in these processes.
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PMID:Peroxisome proliferator-activated receptor-gamma: a versatile metabolic regulator. 1057 7

Conjugated linoleic acid (CLA) has been shown to inhibit carcinogenesis and atherosclerosis, enhance immunologic function while protecting against the catabolic effects of immune stimulation, affect body composition change (reducing body fat gain while enhancing lean body mass gain), and stimulate the growth of young rats. We discuss possible biochemical mechanisms that underlie these physiological effects. We emphasize the importance of considering the effects, both individually and combined, of the two CLA isomers (cis-9, trans-11 CLA and trans-10, cis-12 CLA) that have been shown to exhibit biological activity and which appear to exert their effects via different biochemical mechanisms.
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PMID:Mechanisms of action of conjugated linoleic acid: evidence and speculation. 1063 56

RTP, also called Drg1/Cap43/rit42/TDD5/Ndr1, was originally identified as a homocysteine-responsive gene product, and is now considered to be involved in stress responses, atherosclerosis, carcinogenesis, differentiation, androgen responses, hypoxia, and N-myc pathways. We raised an antiserum against a recombinant human RTP. Western blot analysis showed that RTP expression was induced in human umbilical vein endothelial cells under conditions causing endoplasmic reticulum stress. RTP was partially phosphorylated at seven or more sites. The phosphorylation was reversible, and was enhanced by an increased level of intracellular cAMP and inhibited by both a protein kinase A inhibitor and a calmodulin kinase inhibitor. Protein kinase A directly phosphorylated recombinant RTP in vitro. The phosphorylated forms were abundant in cells at the early log phase, and then decreased with increasing cell density. These data demonstrated that RTP is a phosphorylated stress-responsive protein, and its phosphorylation may be related to cell growth.
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PMID:Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein. 1086 Aug 7


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