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

The vascular endothelium is the site of formation of several powerful mediators. One of these is NO, a chemically unstable radical formed by enzymatic conversion of L-arginine in the presence of molecular oxygen. NO elicits relaxation of VSMC by activating cytosolic guanylate cyclase. NO also counteracts platelet adhesion and aggregation. The biological actions of NO make it a key substance in the endogenous defense against vascular occlusion and thrombosis. The basal formation of NO maintains a moderate but significant vasodilation in the systemic resistance vessels and counteracts platelet activity. When blood flow in conduit arteries is increased there is an augmented endothelial formation of NO, eliciting flow-dependent vasodilation. Beside this, several vasodilators (acetylcholine, bradykinin, histamine, substance P) operate by stimulating endothelial NO formation. On the other hand, drugs like nitroglycerin and papaverine operate independently of the vascular endothelium. Vasodilator mechanisms, physiological as well as pharmacological, may therefore be characterized as endothelium-dependent (i.e. NO-mediated), or endothelium-independent (i.e. not mediated by NO). Physiologically, mixed mechanisms occur. Failure of the vascular endothelium to elicit NO-mediated vasodilatation may be due to decreased formation, increased degradation, decreased sensitivity to the NO formed, or a mixture of these factors. Irrespective of the mechanism behind, this is referred to as endothelial dysfunction. Endothelial dysfunction occurs in several cardiovascular settings, like atherosclerosis, hypercholesterolaemia, diabetes, and essential hypertension. Endothelial dysfunction leads to an impaired tissue perfusion, increased local vascular resistance, decreased defense against thrombus formation, and possibly also decreased defense against hypertrophy of the VSMC in the vessel wall media. In patients with CHD, endothelial dysfunction leads to an impaired coronary flow response to physical and mental stress, and to promotion of platelet adherence and aggregability. Endothelial dysfunction is thereby a probable aggravating factor in the atherosclerotic process, adding a functional component on top of the structural lesions characterizing this disease. A particular form of endothelial dysfunction, limited to the arterial resistance vessels, may explain the symptoms and clinical characteristics of microvascular angina. In patients with essential hypertension, endothelial dysfunction prevails, adding a functional component to the structural factors also in this disease. Hitherto, the only therapeutic tools available to restore endothelial dysfunction appear to be restriction of the dietary intake of lipids, possibly reinforced with intake of antioxidants like fish oil and vitamin E. However, large clinical trials to confirm the efficacy of such therapy in reversing endothelial dysfunction have not been conducted. In the future, more directly acting therapeutic regimens, aimed at supporting or substituting the endogenous formation of NO, are likely to appear as well.
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PMID:Endothelial nitric oxide and cardiovascular disease. 815 Dec 63

Large-scale and systemic epidemiological, pathological and experimental studies emphasized and documented the childhood origin of atherosclerosis. There is increasing consensus that lipid levels in children to a large extent determine the rate of coronary artery disease (CAD) in the adult population. Minimal sudanophilic intimal deposits, and the presence of intracellular and extracellular lipid, and a slight increase in interstitial ground substance in 3 years of age or older patients are found. In the Bogalusa Hearth Study aortic fatty streaks were strongly related the antemortem levels of both total cholesterol and low-density lipoprotein cholesterol (LDL-C) independent of race, sex, and age, and were negatively correlated with the ratio of high-density lipoprotein (HDL-C) to low-density plus very-low-density lipoprotein cholesterol (LDL-C+VLDL-C). The potential for primary prevention is real and the strongest piece of evidence for its is the remarkable trend in CHD mortality rates in recent times, rapidly downward in many western countries. A number of factors influence plasma levels of lipid and lipoproteins in newborn, in infants, in children and adolescents and their relevance as possible predictors of adult coronary artery disease. They are certain inherited disorders of dyslipoproteinemia (familial hypercholesterolemia, familial combined hyperlipidemia, hyperapobetalipoproteinemia, and hypoalphalipoproteinemia) and secondary causes of hyperlipidemia (congenital biliary atresia, glycogen storage diseases, hypothyroidism, diabetes mellitus and nephrotic syndrome, etc).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Atherosclerosis and juvenile dyslipidemias]. 818 5

There is little doubt about the validity of the lipid hypothesis as a pathogenetic theory for atherosclerosis. However, this theory does not allow the conclusion that cholesterol-lowering treatment is necessarily beneficial in practice. As a consequence of the probabilistic nature of risk factors, the classification of plasma cholesterol levels into "normal" and "pathological" can be misleading in clinical practice. The potential benefit of cholesterol-lowering treatment is a direct function of the overall coronary risk, more or less independently of plasma cholesterol. Therefore, plasma cholesterol is of clinical significance only in patients with established CHD and a high overall risk of infarction. Total mortality has been prospectively included as one end-point in addition to infarct mortality in the many intervention studies on cholesterol-lowering. Meta-analyses of these studies show a non-significant decrease in infarct mortality through cholesterol-lowering drug treatment, with a concomitant, highly significant increase in non-infarct mortality. Lowering cholesterol in asymptomatic persons and in coronary patients with a relatively low risk of infarction results in a significant increase in total mortality. Only in a very small group of coronary patients with a very high risk of myocardial infarction, due to the presence of several additional risk factors, may cholesterol-lowering treatment be beneficial.
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PMID:[The effect of lowering cholesterol on mortality]. 826 36

We evaluated 675 men and 190 women who had no symptoms or history of clinical CHD, to determine the prevalence and risk factor correlates of CAC deposits as a marker of atherosclerosis. Measurements were taken noninvasively by ultrafast CT. The presence and extent of CAC deposits as measured by ultrafast CT was determined in all subjects, who also received personal and family medical history and risk factor questionnaire. The prevalence of CAC deposits increased significantly with age, ranging from 15% and 30% in men and women, respectively, < 40 years of age to 93% and 75% in those aged > or = 70 years. Prevalence and total score also increased by the number of risk factors present, although in those aged > 60 years a high prevalence (> 80% in men) of calcium was present regardless of the presence of risk factors. In multiple logistic regression, age, male gender, hypertension, diabetes, hypercholesterolemia, and obesity were independently associated with CAC deposits. These results suggest a high prevalence of atherosclerosis with increasing age and the presence of risk factors in men and women who have no symptoms. Studies to determine the prognostic value of CAC in individuals with no symptoms are needed to determine which populations may benefit most from CAC deposit screening.
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PMID:Coronary calcium and atherosclerosis by ultrafast computed tomography in asymptomatic men and women: relation to age and risk factors. 829 11

The hypothesis that a causal relationship exists between insulin resistance and atherogenesis was first proposed over 23 years ago, and has given rise to a vast literature. Biological plausibility has been lent to the hypothesis by studies in which insulin has produced some effects in cell and tissue culture, and in vivo in arterial tissue, consistent with our understanding of the pathogenesis of atherosclerosis. Clinical studies demonstrating a complex interrelationship between insulin resistance-hyperinsulinaemia and established risk factors for CHD--hypertension, hypertriglyceridaemia, low HDL cholesterol levels and abdominal obesity--are reviewed. A review of the studies examining an independent association between hyperinsulinaemia and coronary heart disease is presented. Cross-sectional studies in both the general population and diabetes support the relationship; however, prospective studies in the general population provide limited and inconsistent support for this hypothesis and highlight the confounding effects of blood pressure, dyslipidaemia and obesity on the effects of hyperinsulinaemia. In subjects with NIDDM and impaired glucose tolerance, prospective studies have not shown a deleterious effect of insulin treatment per se, nor have they consistently shown a significantly increased risk for those with higher endogenous insulin levels. The therapeutic implications of the evidence to date are less complex and involve weight reduction by diet and exercise, the lowering of elevated blood pressure with metabolically neutral agents, the judicious use of lipid lowering drugs and, in diabetes, the use of insulin where clinically indicated.
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PMID:Relationship between insulin resistance and coronary heart disease in diabetes mellitus and the general population: a critical appraisal. 830 14

We investigated the seasonal variation in high density lipoprotein cholesterol (HDL) in 142 dyslipidemic (non-HDL-cholesterol > or = 5.2 mmol/l) middle-aged men in the placebo group of the Helsinki Heart Study over the 5-year trial period. A seasonal pattern was found in HDL fluctuation, with a 4.5% drop during mid-winter (5-year mean 1.192 +/- 0.265 mmol/l) compared with a stable level (5-year mean 1.248 +/- 0.281 mmol/l) during the rest of the year (P < 0.001). A less pronounced seasonal variation in HDL was observed in 85 subjects receiving gemfibrozil. Although affecting pretrial HDL level in cross-sectional analyses, age, alcohol consumption, dietary adherence, physical activity and serum triglycerides had no influence on the seasonality of HDL variation. Smoking had a slight attenuating effect on the variation pattern. Pretrial HDL was influenced by relative weight, but there was also an inverse relationship between HDL and body weight variations, i.e. the annual drop in HDL coincided with the annual peak in body weight. However, seasonal HDL variation was not directly reflected in the annual variation in CHD incidence.
Atherosclerosis 1993 May
PMID:Seasonal variation in high density lipoprotein cholesterol. 835 58

The concentration of apo B is an important risk factor for atherosclerosis, and thus its reduction is associated with a reduction in CHD mortality. In order to reduce apo B concentrations effectively, we must understand how plasma apo B concentration is regulated. Apo B is synthesized, assembled, and secreted by the liver, controlling this process will reduce the number of particles that eventually enter the plasma compartment. The assembly of apo B into a VLDL particle is a complex process which occurs through several stages: peptide synthesis, translocation, accumulation of lipid, and transport through the secretory pathway. Multiple control points regulate the synthesis and secretion of apolipoproteins. Modulation of transcription, translation and intracellular degradation represent independent regulatory mechanisms. The ability of the lipoprotein to bind cotranslationally to lipid appears to be crucial to the formation of a secreted particle. This process may be regulated solely by MTP, or may be modified by the activity of the lipid-synthesizing enzymes. A great deal of evidence supports the role of TG and CE synthesis, although the relative importance of these two lipids is a source of major controversy. In summary, all the lipoprotein components can be limiting for apo B and VLDL synthesis when their availability is substantially decreased. The rate-limiting component in vivo has still not been identified. By understanding how lipoprotein synthesis and assembly are regulated, it should become possible to design new ways of altering these processes in a beneficial manner.
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PMID:Factors affecting the regulation of apo B secretion by liver cells. 858 14

CHD remains the leading cause of death in most developed countries; therefore, elucidation of risk factors and associated mechanisms for atherosclerosis and development of CHD has been a high priority. Data from the Framingham Heart Study and other large-scale epidemiologic studies have identified major risk factors associated with CHD, demonstrating the adverse effects of increased total and LDL-C levels and the protective effect of HDL-C. Other endogenous and exogenous risk factors have been identified and are discussed in this review. In addition, we address known mechanisms involved in the atherosclerotic process.
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PMID:Atherosclerosis: an update. 864

Interest in studies of the fatty acid composition of adipose tissue has arised from the dietary fat-serum cholesterol-CHD issue. The fatty acid composition of depot fat reflects that of the diet. Gas chromatography analysis of subcutaneous adipose tissue yield objective and reliable information of the fatty acid composition of the habitual diet of individuals. A relative linoleic acid deficiency, as depicted by low adipose tissue linoleate levels, has not convincingly been demonstrated to be of importance in the aetiology of atherosclerosis or related disorders. Inverse correlation between n-3 fatty acids and coronary artery disease has been reported. Dietary supplementation of n-3 fatty acids may be of relevance, however the risk of hazardous side-effects do exist. In conclusion, a simple reduction of the total fat content of the diet still seems to be the most important strategy for prevention of atherosclerosis.
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PMID:Fatty acid composition of adipose tissue in humans. Implications for the dietary fat-serum cholesterol-CHD issue. 868 39

The present study was conducted to examine for college males relations between aggressiveness (or expressive hostility) and dominance and (a) particular developmental experiences and (b) total serum cholesterol. Aggressiveness but not dominance was found to be positively related to subjects' reports of their parents' behavior which reflected (a) less genuine acceptance, (b) more interference in the person's desires as a child, and (c) more punitiveness. For low-physically fit subjects, both aggressiveness and dominance were found to be positively related to levels of total serum cholesterol. These relations are congruent with the notion that both aggressiveness and dominance may contribute to hastening coronary atherosclerosis and risk of CHD via elevated levels of plasma lipids. It should be noted, however, that the relations obtained in the present study were all modest in size. For high-physically fit individuals associations were not found between total serum cholesterol and either aggressiveness or dominance. These results suggest that good physical fitness may attenuate the degree to which either aggressiveness or dominance may adversely affect health via elevated levels of cholesterol.
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PMID:Aggressiveness, dominance, developmental factors, and serum cholesterol level in college males. 874 86


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