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

The effect of iron deficiency anemia on the development of atherosclerosis was investigated in chicks. The control group of birds were fed a basal diet, the atherosclerosis group received 1% cholesterol. The lipid content of the aortas of the chicks in atherosclerosis and atherosclerosis-anemia group also developed anemia of appreciable severity in 12 weeks. Hemoglobin and PCV were taken as the index of anemia, while the lipid constituents were determined in plasma and aortic tissue for atherosclerosis. Hypercholesterolemia of almost equal severity occurred in both atherosclerosis and atherosclerosis-anemia groups. The abnormal rise of cholesterol and other lipid material in the aortas of the atherosclerosis and atherosclerosis-anemia groups of birds indicates that iron deficiency anemia did not markedly affect the development of atheroslcerosis; it did not offer any protection in chickens and, in fact, a slight potentiating effect was observed.
Atherosclerosis
PMID:Effect of iron deficiency anemia on the development of atherosclerosis in chicks. 114 33

Advanced glycosylation end products (AGEs) form spontaneously from glucose-derived Amadori products and accumulate on long-lived tissue proteins. AGEs have been implicated in the pathogenesis of several of the complications of aging and diabetes, including atherosclerosis and renal disease. With the use of recently developed AGE-specific antibodies, an AGE-modified form of human hemoglobin has been identified. Termed hemoglobin-AGE (Hb-AGE), this modified species accounts for 0.42 percent of circulating hemoglobin in normal individuals but increases to 0.75 percent in patients with diabetes-induced hyperglycemia. In a group of diabetic patients treated with the advanced glycosylation inhibitor aminoguanidine, Hb-AGE levels decreased significantly over a 1-month period. Hemoglobin-AGE measurements may provide an index of long-term tissue modification by AGEs and prove useful in assessing the contribution of advanced glycosylation to a variety of diabetic and age-related complications.
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PMID:Hemoglobin-AGE: a circulating marker of advanced glycosylation. 141 74

Twenty-one 8-14 kg adult male stumptailed macaques, Macaca arctoides, were fed a standard laboratory diet and divided into 3 groups. The high-dose group and low-dose group were exposed to cigarette smoke at the human equivalent of 3 packs and 1 pack per day, respectively, 7 days per week, for 3-5 years. Eight animals served as cage an sham controls. Peak blood carboxyhemoglobin (COHb) levels measured immediately after smoking showed levels of 0.5+/- 0.1%, 3.6+/-1.0%, and 5.7+/-2.8% for sham controls, low, and high dose smokers, respectively. Hemoglobin and hematocrit values were 2-7% higher (N.S. to P less than 0.05) for smoking groups, presumably as a consequence of chronically elevated COHb levels. No significant differences were seen in total plasma cholesterol and lipoprotein cholesterol concentration measured at four intervals over period of one year. We conclude from these data that, while fed a low fat diet, chronic cigarette smoke inhalation fails to alter plasma lipoprotein levels in this animal model.
Atherosclerosis 1982 Jan
PMID:Failure of chronic cigarette smoke exposure to alter plasma lipoproteins of stumptailed macaques (Macaca arctoides). 695 81

Twelve ambulatory patients (six women and six men; mean age, 29 years) with type I diabetes were treated with a continuous subcutaneous open-loop insulin pump in an attempt to effect better glucose control. Hemoglobin A1, mean blood glucose, total cholesterol, total triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and the cholesterol/HDL-C ratio were assessed monthly before and after glucoregulation from five to 14 months (mean, nine months). Mean HDL-C levels increased significantly (52 +/- 4 to 60 +/- 5 mg/dL); mean cholesterol/HDL-C ratios decreased significantly (4.46 +/- 0.43 to 3.89 +/- 0.39). Mean values for triglycerides, total cholesterol, and LDL-C, all initially normal, did not change. Both mean Hb A1 levels and glucose levels fell from 11.2% +/- 0.5% to 9.8% +/- 0.5% and 177 +/- 15 mg/dL to 128 +/- 12 mg/dL, respectively. Insulin requirements decreased from 0.80 +/- 0.08 to 0.61 +/- 0.05 units/kg/24 hr. These results may favorably alter the prediction for development of accelerated atherosclerosis in type I diabetics.
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PMID:Improvement of high-density lipoprotein-cholesterol levels. Ambulatory type I diabetics treated with the subcutaneous insulin pump. 703 Dec 87

Oxidative modification of human low-density lipoprotein (LDL) is thought to play a major role in the development of atherosclerosis. Free hemin, hemoglobin, myoglobin, and horseradish peroxidase (HRP) were reported in different studies as promoters of LDL lipid oxidation. Based on our previous finding that hemin induced oxidative crosslinking of the LDL protein, apolipoprotein B (apo B) (Y. I. Miller and N. Shaklai (1994) Biochem. Mol. Biol. Int. 34, 1121-1129), we compared the ability of free hemin and the above hemoproteins to induce peroxidation modification of apo B using SDS-PAGE. The levels of the final products of lipid peroxidation were determined as thiobarbituric acid-reactive substances. Hemoglobin and myoglobin were found to be as active as free hemin and all these were much more active than the classic peroxidase HRP. Moreover, the products of oxidized apo B differed: hemoglobin, myoglobin, and hemin induced mostly covalent aggregates, while HRP caused fragmentation of apo B. Hemoglobin reactivity was expressed at low H2O2 concentrations even in the absence of molecular oxygen. Desferal, along with other antioxidants, inhibited the hemoglobin-induced LDL oxidation independently of its iron-chelating property. The high peroxidative reactivity of hemoglobin is explained by its ability (unlike HRP) to transfer the oxidative equivalents from the heme active site, through the globin, to LDL. The apo B radicals thus formed are terminated, yielding intermolecular crosslinked protein. It is suggested that small amounts of the highly reactive hemoglobin in plasma, suffice to trigger LDL protein oxidation (along with its lipid oxidation), thereby inflict the atherosclerosis precondition.
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PMID:Hemoglobin induced apolipoprotein B crosslinking in low-density lipoprotein peroxidation. 861 Oct 31

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, recognized as an inflammatory disease of the vessel wall, probably accelerated by diabetes mellitus (DM). Elevated interleukin (IL)-6 levels have been associated with increased cardiovascular morbidity and a common polymorphism has been identified in the promoter region of the IL-6 gene. The aim of this prospective study was to investigate inflammatory mediators in PAD patients (+/- DM) and to investigate a possible relationship to the IL-6 gene polymorphism. Five groups of patients (DM, intermittent claudication +/- DM, critical limb ischemia (CLI) +/- DM) and a control group of 20 individuals each were included. Hemoglobin, high sensitive C-reactive protein (hsCRP), creatinine, blood lipids, white blood cells (WBC); CD11b/CD18; vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1), sE-selectin, sP-selectin; IL-6, IL-8, tumour necrosis factor (TNF)alpha, sTNFalpha-R1 and sTNFalpha-R2 were analysed. The IL-6 gene polymorphism was determined in all groups and also compared with 200 healthy controls from a larger study of blood donors. In a multiple regression analysis, adjusted for gender, smoking and age, the effect of CLI was significantly (p < 0.05) associated with elevated levels of the WBC count, hsCRP, proinflammatory cytokines (IL-6, TNFalpha-R1-2) and endothelial (sICAM, sVCAM) and WBC (CD11b gran) markers. The effect of less advanced PAD (intermittent claudication) was related to an increased concentration of sVCAM-1 and the number of monocytes and granulocytes. DM or leg ulcers were not significantly related to any of the markers. No significant difference in frequency of the various IL-6 genotypes was found between the groups or when compared with the group of 200 blood donors (p> 0.3). Activation of cytokines, endothelial cells and WBC was related to the Fontaine stage of PAD but not to the presence of DM or ulcers. No association was found between the polymorphism in the IL-6 promoter region and PAD.
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PMID:Inflammatory markers and IL-6 polymorphism in peripheral arterial disease with and without diabetes mellitus. 1623 72

Hemoglobin (Hb) released during hemolysis is a potent oxidant. Extracorpuscular Hb may enter the vessel wall and mediate low-density lipoprotein oxidation, thereby promoting the development and progression of atherosclerosis. Haptoglobin (Hp) is an antioxidant protein as a result of its ability to bind Hb and block Hb-induced oxidative damage. Hp also facilitates the removal of Hb from the extravascular compartment via the CD163 macrophage scavenger receptor. In man, there are two common alleles for Hp denoted 1 and 2, and correspondingly, three different possible genotypes: Hp1-1, Hp2-1, and Hp2-2. We have recently demonstrated in several longitudinal studies that Hp genotype is an independent risk factor for diabetic vascular complications. Specifically, we have shown that diabetic individuals with Hp2-2 are more likely to develop nephropathy, retinopathy, and cardiovascular disease as compared with those with Hp2-1 or Hp1-1. Mechanistically, we have found significant Hp type differences in the antioxidant and CD163-mediated scavenging and activation functions of the different Hp protein types. Furthermore, we have demonstrated that these functions are modified in the diabetic state. In this review, we focus on the clinical studies associating the Hp polymorphism and diabetic vascular complications, and the molecular basis behind this interaction.
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PMID:In vivo and in vitro studies establishing haptoglobin as a major susceptibility gene for diabetic vascular disease. 1731 95

More than 50% of end-stage renal disease subjects treated by chronic hemodialysis die from cardiovascular events. Although there is some information regarding to anemia compensation and to the levels of biochemical risk factors of atherosclerosis in other countries, the data from the Czech Republic are missing. The aim of this study was to estimate mean cholesterol, triglyceride and hemoglobin levels in hemodialyzed subjects in the Czech Republic and to compare them with current guidelines. During the years 2001-2006, nephrologists of all subjects screened by duplex Doppler ultrasonography of our department were asked to fill in questionnaires with basic history and laboratory data. Hemoglobin concentration was calculated separately for years 2001-2004 and 2005-2006 because of the change of recommended target value from 105 to 110 g/l in 2004. A total of 258 subjects were included, aged 65 +/- 14 years, 93 of them males. Patients came from 46 different hemodialysis centers in the Czech Republic. The presence of hypertension and diabetes was in 72.5% and 39.5%, respectively. Only 13.2% of subjects had the smoking history, and another 10% currently smoked. The mean +/- SD laboratory results were as follows: total cholesterol 5.0 +/- 1.1 mmol/l, triglycerides (2.5 +/- 1.4 mmol/l). Hemoglobin concentration was 104.4 +/- 14.4 g/l (mean +/- SD) in years 2001-2004 and 110.1 +/- 16.2 g/l in years 2005-2006. Hemoglobin full blood concentration was lower than recommended 105 g/l in 55% of hemodialyzed subjects during years 2001-2004, and it was lower than 110 g/l during years 2005-2006 in 47% of patients. Hypercholesterolemia above recommended 5.17 mmol/l was present in 39% of subjects. Triglycerides were elevated above 1.69 mmol/l in 64% of patients. Only 10% of subjects were treated by lipid-lowering drugs. We can conclude that in the Czech Republic, patients treated by chronic hemodialysis frequently suffer from anemia, despite the growing evidence of erythrocyte stimulating agents treatment benefit. Similarly, considerable number of these subjects has hypercholesterolemia and hypertriglyceridemia, only rarely treated by lipid-lowering drugs. However, this therapy is still not adequately supported by clinical research evidence.
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PMID:Dyslipidemia and anemia in chronically hemodialyzed patients. 1822 44

Epidemiological studies and experimental data suggest iron involvement in atherosclerosis. The relation between iron and atherosclerosis is complex and remains contradictory. In thalassemia patients, non transferrin bound iron (NTBI) and free hemoglobin (Hb) are present in plasma and may accelerate atherogenesis, but its progression may be inhibited by iron chelators. The mechanism whereby iron may stimulate atherogenesis has been intensively investigated. Non transferrin bound iron and sera from subjects with hemochromatosis induced endothelial activation with expression of vascular adhesion molecules and endothelial inflammatory chemokines. Such events could be inhibited by iron chelators and oxygen radical scavengers with intracellular activity. Iron chelators may be effective in preventing vascular damage in patients with high concentrations of NTBI as found in thalassemia.
Hemoglobin 2008
PMID:Can iron chelators influence the progression of atherosclerosis? 1827 90

Hemoglobin A1c (HbA1c), a long-term, integrated average of tissue exposure to hyperglycemia, is the best reflection of average glucose concentrations and the best proven predictor of microvascular complications of diabetes mellitus. However, HbA1c fails to capture glycemic variability and the risks associated with extremes of hypoglycemia and hyperglycemia. These risks are the primary barrier to achieving the level of average glucose control that will minimize both the microvascular and the long-term macrovascular complications of type 1 diabetes. High blood glucose levels largely due to prandial excursions produce oxidative and inflammatory stress with potential acceleration of preexisting atherosclerosis and increased cardiovascular risk. Moreover, some temporal aspects of glycemic variation, including the rates of rise and fall of glucose, are associated with adverse cognitive and mood symptoms in those with diabetes. Methods to quantify the risk of glycemic extremes, both high and low, and the variability including its temporal aspects are now more precise than ever. These important endpoints should be included for use in clinical trials as useful metrics and recognized by regulatory agencies, which has not been the case in the past. Precise evaluation of glycemic variability and its attendant risks are essential in the design of optimal therapies; for these reasons, inclusion of these metrics and the pulsatile hormone patterns in mathematical models may be essential. For the clinician, the incursion of mathematical models that simulate normal and pathophysiological mechanisms of glycemic control is a reality and should be also gradually incorporated into clinical practice.
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PMID:The median is not the only message: a clinician's perspective on mathematical analysis of glycemic variability and modeling in diabetes mellitus. 1975 68


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