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

Many preclinical and clinical studies reveal that changes in lipoprotein metabolism are a major contributing factor to atherosclerosis. Hormones in oral contraceptive (OC) formulations strongly influence lipoprotein metabolism. Specifically, estrogens bring about increases in plasma triglycerides which then cause a rise in the very low density lipoprotein. They also decrease levels of the intermediate and low density lipoprotein which cause build up of plaque on arterial walls. Estrogens also lead to rising high density lipoprotein (HDL) levels, especially the HDL2 subspecies. Increased HDL levels are associated with lower mortality rates from cardiovascular conditions in women who have already experienced menopause and are on hormone replacement therapy. Combination OCs used in the US increase plasma triglycerides, low density lipoprotein, and HDL3. The estrogen dose and the relative androgenicity of the progestin together influence the changes in HDL and HDL2. Even though low dose combined OCs bring about lipoprotein changes which are lower than those of higher dose OCs, the changes often remain significant. The progestin component of OCs is responsible for most changes in carbohydrate metabolism. Specifically OC use can lead to increased levels of plasma insulin, insulin resistance, and relative glucose intolerance. A curve analysis of glucose tolerance tests reveals this intolerance effect of OCs. The changes in carbohydrate metabolism are not as great in women using the lower dose OCs or formulations using the new progestins, however.
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PMID:The metabolic impact of oral contraceptives. 141 43

Fifteen non-obese patients with familial hypercholesterolemia and fifteen normocholesterolemic subjects matched for age, body mass index, waist/hip ratio, arterial blood pressure and sedentary life style underwent blood sampling for determination of fasting plasma glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides, free fatty acids, apolipoprotein A1 and B. In both groups of subjects we determined erythrocyte membrane microviscosity and performed an echocardiographic study. We demonstrated that hypercholesterolemic patients had a significant increase in fasting plasma total cholesterol (8.9 +/- 0.5 vs. 5.5 +/- 0.3 mmol/l, P less than 0.001), insulin (79 +/- 4 vs. 58 +/- 4 pmol/l, P less than 0.05) and apolipoprotein B (2.2 +/- 0.5 vs. 1.3 +/- 0.5 g/l P less than 0.01). In the echocardiographic study we found a significant impairment in left ventricular relaxation (isovolumic relaxation time (IRT) 106 +/- 6 vs. 73 +/- 7 ms, P less than 0.01). Erythrocyte membrane microviscosity (0.253 +/- 0.004 vs. 0.225 +/- 0.003, P less than 0.05) was also increased in hypercholesterolemic patients. Finally we found that erythrocyte membrane microviscosity correlated with fasting plasma insulin levels (r = -0.46, P less than 0.03) and IRT (r = -0.52, P less than 0.01).
Atherosclerosis 1992 Sep
PMID:Impaired left ventricular relaxation and hyperinsulinemia in patients with primary hypercholesterolemia. 141 3

An increased risk of developing premature atherosclerosis is associated with stress, diabetes, obesity, and hypertension. These conditions are associated with insulin resistance, hyperglycemia, hypertriglyceridemia and hypercholesterolemia. An alternative way of interpreting insulin resistance is to consider that metabolism in this condition would be regulated to a greater extent by stress hormones and in particular by cortisol. Glucocorticoids and fatty acids (which are produced in response to stress) antagonise the actions of insulin in promoting glucose uptake and protein synthesis, in decreasing gluconeogenesis and protein catabolism, and promoting the clearance of intermediate density lipoprotein and low density lipoprotein from the circulation by the liver. They also promote the secretion of very low density lipoprotein thus producing hypertriglyceridemia and hypercholesterolemia. By contrast to this antagonism, cortisol can also facilitate the action of insulin in stimulating the storage of energy via glycogen and fatty acid synthesis and through lipoprotein lipase in adipose tissue. These effects are significant in relation to obesity and to weight gain. An increased control of metabolism by cortisol therefore produces changes in metabolism that are potentially atherogenic and it is associated with insulin resistance and the other risk factors for atherosclerosis. Benfluorex treatment improves insulin sensitivity and has antihyperglycemic and hypolipidemic effects in human beings and in experimental animals. These effects can be observed independently of weight loss, but lowering food intake also produces a metabolic benefit. Long-term treatment with benfluorex can also decrease stress responses in terms of glucocorticoid release and the stimulation of lipolysis probably by its serotoninergic control of the hypothalamic-pituitary-adrenal axis. Such an action provides for an integrated treatment of the obese-diabetic-hyperlipidemic syndrome. Benfluorex produces overall changes in metabolism that tend to normalise the major risk factors associated with premature atherosclerosis. This provides a potential advantage over other therapies for atherosclerosis which may ameliorate a symptom (e.g., hyperlipidemia) without treating the underlying metabolic disturbance that predisposes to atherogenesis.
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PMID:[Mode of action of benfluorex. Recent data]. 143 2

In order to investigate the role of hyperglycemia on the development of atherosclerosis in diabetics, the effects of high glucose-induced modification of serum factors on the proliferation of bovine carotid artery endothelial cells were studied. Dialysates of high glucose-treated serum inhibit cell growth in a time- and glucose concentration-dependent manner. With 6 weeks of pretreatment, 16.7 mM glucose causes a 47.2% inhibition in cell growth compared to 5.6 mM glucose (P < 0.001). Pretreatment of serum in the presence of reduced glutathione (0.5-1.0 mM), an antioxidant, significantly prevents the high glucose-induced inhibition without inhibiting the formation of early non-enzymatic glycosylation products. Dithiothreitol (7.5 mM) treatment after preincubation with glucose fully restores the glucose-induced inhibition. When the dialysates are fractionated according to molecular mass, the high glucose-induced inhibition is maximal in the MW fraction above 100 kDa. These data suggest that high glucose conditions facilitate the susceptibility of serum proteins to sulfhydryl oxidation forming disulfide crosslinks and this oxidative process may contribute to the inhibition of endothelial cell proliferation.
Atherosclerosis 1992 Nov
PMID:An oxidative mechanism is involved in high glucose-induced serum protein modification causing inhibition of endothelial cell proliferation. 144 97

In the last 15 years it has been a growing interest in the cyclic variations of circulating insulin [46]. After the suggestion that this phenomenon may be due to oscillations of the beta-cell membrane potential [8,39], it was demonstrated that [Ca2+]i oscillates in the glucose-stimulated beta-cell with a similar frequency to that of pulsatile insulin release. The present review describes four types of [Ca2+]i oscillations in the pancreatic beta-cell. The slow sinusoidal oscillations, referred to as type-a, are those which most closely correspond to pulsatile insulin release. Although not affecting the properties of the type-a oscillations in individual beta-cells, the concentration of glucose is a determinant for their generation and further transformation into a sustained increase. Accordingly, cytoplasmic Ca2+ is regulated by sudden transitions between oscillatory and steady-state levels at threshold concentrations of glucose, which are characteristic for the individual beta-cell. This behaviour explains the observation of a gradual recruitment of previously non-secreting cells with increase of the extracellular glucose concentration [44]. However, it still remains to be elucidated how the sudden transitions between these three states translate into the co-ordinated slow oscillations of [Ca2+]i in the intact islet. Cyclic variations of circulating insulin require a synchronization of the [Ca2+]i cycles also among the islets in the pancreas. It is still an open question by which means the millions of islets communicate mutually to establish a pattern of pulsatile insulin release from the whole pancreas. The discovery that the beta-cell is not only the functional unit for insulin synthesis but also generates the [Ca2+]i oscillations required for pulsatile insulin release has both physiological and clinical implications. The fact that minor damage to the beta-cells prevents the type-a oscillations with maintenance of a glucose response in terms of raised [Ca2+]i reinforces previous arguments [54] that loss of insulin oscillations is an early indicator of type-2 diabetes. Further analyses of the [Ca2+]i oscillations in the beta-cells should include not only the mechanisms for their generation and subsequent propagation within or among the islets but also how modulation of their frequency affects the insulin sensitivity of various target cells. The latter approach may be important in the attempts to maintain normoglycemia under conditions minimizing the vascular effects of insulin supposed to precipitate hypertonia and atherosclerosis [70,71,77].
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PMID:Cytoplasmic Ca2+ oscillations in pancreatic beta-cells. 145 Feb 3

Controlled comparisons of the effects of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) as a part of lipid-lowering diets in persons with hyperlipoproteinaemia are sparse. The present study was carried out at a metabolic ward. Forty hyperlipidaemic patients (25 hypercholesterolaemic and 15 hypertriglyceridaemic) were given a 3-week diet rich in either MUFA (saturated fatty acids 7.3 energy% (E%), MUFA 14.6 E%, PUFA 4.8 E%) or PUFA (saturated fatty acids 7.8 E%, MUFA 8.4 E%, PUFA 10.4 E%), but otherwise with an identical composition. The mean serum cholesterol reduction on the MUFA diet was 12% (P < 0.001), with a low density lipoprotein cholesterol reduction of 11% (P < 0.001). The corresponding reductions on the PUFA diet were 15% (P < 0.001) and 16% (P < 0.001). The serum apolipoprotein B and A-I concentrations decreased highly significantly by 13% and 11% on the MUFA diet and by 14% and 11% on the PUFA diet. None of these changes differed between the two diets. Neither were there any differences between the diets regarding the effects on blood glucose, serum insulin and plasma fibrinogen, but there was a significant decrease in serum insulin with a significant reduction of the insulin/glucose ratio after the MUFA diet. The results of this study indicate that MUFA and PUFA are interchangeable within the given frames in lipid lowering diets even in patients with hyperlipidaemia.
Atherosclerosis 1992 Oct
PMID:Effects of lipid-lowering diets enriched with monounsaturated and polyunsaturated fatty acids on serum lipoprotein composition in patients with hyperlipoproteinaemia. 146 45

To assess the relationship between the fibrinolytic system and coronary risk factors, several fibrinolytic parameters were measured in 72 male survivors of myocardial infarction and in 53 age-matched healthy controls. The coronary patients had significantly higher plasminogen activator inhibitor (PAI) activity than the control subjects, while t-PA antigen did not differ between the groups. After stratifying the coronary patients in 14 diabetic and 58 nondiabetic patients, the elevated PAI activity remained limited to the diabetic group. PAI activity correlated significantly with systolic blood pressure, blood glucose, body mass index and LDL cholesterol. In multivariate regression analysis, significant associations persisted between PAI and diabetes, body mass index and LDL cholesterol. Coronary disease had no impact on the regression model. Our results suggest that the increased PAI-1 in selected groups of coronary patients is not a consequence of coronary disease itself, but is rather related to the metabolic risk factors of atherosclerosis, especially diabetes.
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PMID:Increased plasminogen activator inhibitor activity in survivors of myocardial infarction is associated with metabolic risk factors of atherosclerosis. 146 21

Coronary Heart Disease (CHD) is less common in females compared to males and geographical differences are observed in both sexes; furthermore time trend mortality in women follows the same pattern as in men suggesting that the environmental factors have similar influence in both sexes. Nutrition is an environmental factor which plays an important role in the etiology and pathogenesis of CHD. The Italian Nine Communities Study on Atherosclerosis Risk Factors analyzes the relationships between consumption of food rich in saturated fatty acids and cholesterol and a number of CHD risk factors in a sample of Italian women aged 20-59 years. The dietary habits of the participants were ascertained by a food frequency questionnaire. Intake of atherogenic food was evaluated for each participants systolic blood pressure, serum glucose, serum cholesterol increased with increasing consumption of atherogenic food (i.e. butter). Conversely, consumption of olive oil and vegetable oil was inversely associated with serum cholesterol, serum glucose and systolic blood pressure. Furthermore, calcium rich food consumption was associated with lower blood pressure. These findings were independent from any possible confounding effect of age, adiposity, alcohol intake and cigarette smoking. Data from the Intersalt Study in Italy (400 women aged 20-59 years) have clearly shown lower blood pressure levels in participants with lower intake of sodium and alcohol and higher intake of potassium. Some clinical and experimental observations suggest a possible difference in response to dietary factors in women compared to men due to the intermediate effects of the sex hormone pattern.
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PMID:[Diet and cardiovascular risk among women in Italy]. 149 32

Abnormal lipoprotein metabolism contributes to the increased risk of premature atherosclerosis in people with insulin-dependent (type I) diabetes. Although hypertriglyceridemia is common in those with untreated IDDM, treatment with conventional insulin therapy usually restores fasting lipoprotein profiles to nondiabetic levels. Intensive insulin therapy improves glycemic control and lipoprotein concentrations, but does not ameliorate the changes in lipoprotein composition described in people with IDDM. Some of these persistent changes in lipoprotein composition have been attributed to peripheral hyperinsulinemia associated with s.c. insulin therapy. The recent availability of implantable insulin-infusion pumps for treatment of IDDM has allowed the study of the effect of i.p. insulin delivery on lipoprotein metabolism. i.p. insulin therapy is capable of maintaining near normal plasma glucose levels while reducing the peripheral hyperinsulinemia. Although results have been contradictory, studies of i.p. insulin therapy may eventually help to determine whether some of the observed changes in lipoprotein metabolism and composition in people with IDDM are due to the peripheral hyperinsulinemia associated with s.c. insulin therapy.
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PMID:Plasma lipid and lipoprotein disorders in IDDM. 152 27

Recent progress in structure elucidation of products of the advanced Maillard reaction now allows probing specifically for the role of this reaction in the pathogenesis of age- and diabetes-related complications. Pyrraline is a glucose-derived advanced glycation end product against which polyclonal and monoclonal antibodies have been raised. Immunohistochemical localization studies revealed that pyrraline is found predominantly in the sclerosed extracellular matrix of glomerular and arteriolar renal tissues from both diabetic and aged nondiabetic individuals. Pentosidine and carboxymethyllysine are Maillard end products derived from both glucose and ascorbate. In addition, pentosidine can be formed from several other sugars under oxidative conditions, and in vitro studies suggest that a common intermediate involving a pentose is a necessary precursor molecule. The highest levels of these advanced Maillard products are generally found in the extracellular matrix, but these products are also present in lens proteins and in proteins with a fast turnover such as plasma proteins. Diabetes, and especially uremia, greatly catalyzes pentosidine formation. Both conditions are characterized by accelerated cataractogenesis, atherosclerosis, and neuropathy, suggesting that molecular damage by advanced Maillard reaction products may be a common mechanism in their development.
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PMID:Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. 152 33


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