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

The changes in levels of glycosaminoglycans (GAGs) of the intima and media of the human artery in atherosclerosis were determined by a recently introduced two-dimensional electrophoresis technique that permits direct measurments of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE-Sephadex A-25 column, and the resulting three fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestability by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies we concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, we demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N-acetylgalactosamine-6-sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentrations. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.
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PMID:The glycosaminoglycans of the human artery and their changes in atherosclerosis. 13 44

Hypercoagulability of blood, monocytic infiltration, and changes in pericellular and extracellular matrix glycosaminoglycans (GAGs) are observed in atherosclerosis, inflammation, and neoplasia. In the present studies, monocyte procoagulants and different GAGs including chondroitin sulfate (CS) A, CSB, CSC, CSD, CSE, and heparan sulfate, were tested either in clotting assays with whole plasma or in chromogenic assays with purified coagulation proteases. Procoagulant activity in plasma was inhibited by three of the seven GAGs, including heparan sulfate, CSE, and CSB. In contrast, activity of purified coagulation protease was inhibited only by CSE, and the inhibition was observed with intrinsic (factor VIIIa/IXa) but not extrinsic (tissue factor/factor VII) components. Reciprocal titration experiments with enzyme and substrate and Scatchard type analyses were consistent with concentration-dependent inhibitory interactions between CSE and sites on both factor VIIIa and IXa. On purified phospholipids, CSE concentration resulting in half-maximal inhibition (Ki) was 5 ng/ml for interaction with factor IXa and > 500 ng/ml for interaction with factor VIIIa. The Ki values were lower for reactions on purified lipid than for reactions on monocyte surfaces and for reactions on resting than on endotoxin-stimulated monocytes. Experiments with CSE oligosaccharides of defined size indicated that the smallest CSE fragment capable of inhibitory activity was composed of 12-18 monosaccharide units. Collectively, these results indicate that factor X-activating reactions are inhibited by GAGs expressed on monocyte membranes. Inhibition is specific with respect to the structure of both the GAG and the activating protease. Lack of inhibition by added CSA, CSB, and CSC in contrast to CSE strongly suggests a direct role of 4,6-di-O-sulfated N-acetylgalactosamine GAG structures in the inhibition of intrinsic pathway protease. These findings also suggest potential pharmacologic use of CSE as specific anticoagulant in the management of prothrombotic states mediated by intrinsic pathway coagulation reactions.
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PMID:Specific regulation of procoagulant activity on monocytes. Intrinsic pathway inhibition by chondroitin 4,6-disulfate. 759 13

Structural changes of the peripheral vascular component as seen during hypertension and atherosclerosis have been suggested during heart failure but have never been reported. Therefore, we studied possible structural alterations in the peripheral vasculature in an experimental model of heart failure, induced by ligation of the left coronary artery in rats. Large conduit and resistance-type arteries were excised at 1, 3, 5, and 12 weeks after myocardial infarct induction (MI) or sham surgery. Vessel dimensions (medial cross-sectional area [CSA], internal and external diameters, and media-to-lumen ratios) as well as medial collagen and elastin volume fractions were measured by computerized morphometry. The hydroxyproline assay was used to determine collagen and elastin content biochemically. In separate groups of animals, peripheral tissue flows were measured by using radioactive microspheres 5 and 12 weeks after MI. To evaluate the effects of the degree of heart failure, the animals of the 12-week group (n = 10) were subdivided into groups of moderate (< 45% infarct size) and large (> 45% infarct size) infarction. At all time points, body weights of sham-operated and MI rats were comparable. Lung weights of infarcted animals were increased proportionally to infarct size. No major changes in vessel dimensions were seen at the earlier time points. Twelve weeks after coronary artery ligation, significantly smaller CSAs were observed in several large conduit arteries such as the thoracic aorta, carotid artery, and superior mesenteric artery. These changes coincided with reductions in both internal and external diameters. In contrast, internal and external diameters of mesenteric and pulmonary resistance arteries were increased after 12 weeks of coronary artery ligation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral vascular alterations during experimental heart failure in the rat. Do they exist? 767 Sep 66

To determine whether a relationship between echographically assessed carotid artery and left ventricular (LV) structures existed in asymptomatic men at risk for cardiovascular disease, we evaluated carotid and LV parameters in 69 subjects (23-62 years) without LV hypertrophy. The right common carotid far wall intima-media thickness (IMT) was measured using an automated technique and the cross-sectional intima-media complex area (IMC-CSA) was calculated, assuming a circular profile of carotid wall layers, as (IMC-CSA = pi x IMT x (IMT + D)), D being the lumen diameter. LV mass was evaluated using the M-mode echocardiography. Among study subjects 30% were hypertensive, 67% hypercholesterolemic, 21% current smokers and 52% had a positive smoking history. In the study population LV mass correlated both with IMT (r = 0.54, P < 0.001) and IMC-CSA (r = 0.62, P < 0.001). In multivariate analysis LV mass was associated with IMC-CSA (P < 0.001), body mass index (P < 0.01), lifelong smoking dose (P < 0.01) and systolic blood pressure (P < 0.05), r2 = 0.58, P < 0.001. Therefore, IMC-CSA may be a clinically relevant independent indicator of LV mass even within its normal ranges.
Atherosclerosis 1996 Nov 15
PMID:Carotid artery and left ventricular structural relationship in asymptomatic men at risk for cardiovascular disease. 900 10

Our objective was to provide a description of 'normal' carotid artery dimensions which are increasingly used for detecting early atherosclerosis and predicting clinical complications. Far wall intima-media thickness (IMT), lumen diameter and cross-sectional area intima-media thickness (CSA-IMT) were measured on 1 cm-distal common carotid artery segments on both sides by B-mode ultrasound, using an automated computerized edge-detection program, in 133 men and 216 women aged 17-65 years and free from cardiovascular disease and traditional risk factors. IMT and CSA-IMT increased with age in both sexes and on both sides, while diameter did not, except on the right side in men. Women had lower diameter than men except on the left side at 30 years or below, while IMT did not differ between sexes except on the left side from 31 to 50 years where IMT was higher in men; as a result of their lower diameter, women had lower CSA-IMT than men except on the right side above 50 years. IMT was lower on the right side than on the left side in both sexes, except in 30-year old or younger men and 31- to 40-year old women, while diameter was higher on the right side than on the left side in men and women aged 31-40 years and in women aged 41-50 years; also CSA-IMT was lower on the right side than on the left side in both sexes above 40 years. These data provide reference values of carotid artery dimensions and show that age, sex and side of measurement should be taken into account in the interpretation of 'normal' values of IMT and diameter in clinical practice and trials.
Atherosclerosis 2000 Feb
PMID:Distribution of ultrasonographically-assessed dimensions of common carotid arteries in healthy adults of both sexes. 1065 65

Disturbances in platelet functions are found in kidney diseases and may contribute to the progression of atherosclerosis with its thrombotic complications. Kidney allograft recipients are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess effects of various immunosuppressive drugs on aggregation of platelets obtained from healthy volunteers and chronically hemodialyzed patients. Platelet aggregation in the whole blood and in PRP was induced by collagen (2-microgram/ml whole blood and PRP) arachidonic acid (0.75 mM whole blood and PRP), ADP (10 microM--whole blood and 5 microM--PRP), ristocetin (0.75 mg/ml--whole blood and 1.5 mg/ml--PRP) and was studied after preincubation with clinically relevant concentrations of cyclosporine A, FK 506, 15-deoxyspergualin, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil. Preincubation with cyclosporine A resulted in a significant increase in platelet aggregation, whereas preincubation with FK 506, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil caused a decrease in platelet aggregation. 15-deoxyspergualin did not affect platelet aggregation. Enhanced platelet aggregation in CSA-treated kidney allograft recipients may have clinical implications in regard to the reported tendency to thrombosis in those patients, and to CSA-induced nephrotoxicity. Thus, inhibition of platelet activity in these patients might be of clinical benefit.
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PMID:Effects of immunosuppressive drugs on platelet aggregation in vitro. 1222 5

Sleep plays a large role in patients with heart failure. In normal subjects, sleep is usually in a supine position with reduced sympathetic drive, elevated vagal tone and as such a relatively lower cardiac output and minute ventilation, allowing for recuperation. Patients with heart failure may not experience the same degree of autonomic activity change and the supine position may place a large strain on the pulmonary system. More than half of all heart failure patients have one of two types of sleep apnea: either obstructive or central sleep apnea. Some patients have both types. Obstructive sleep apnea is likely to be a cause of heart failure due to large negative intrathoracic pressures, apnea related hypoxemia and hypercapnia, terminated by an arousal and surge in systemic blood pressure associated with endothelial damage and resultant premature atherosclerosis. Reversal of obstructive sleep apnea improves blood pressure, systolic contraction and autonomic dysfunction however mortality studies are lacking. Central sleep apnea with Cheyne Stokes pattern of respiration (CSA-CSR) occurs as a result of increased central controller (brainstem driving ventilation) and plant (ventilation driving CO2) gain in the setting of a delayed feed back (i.e., low cardiac output). It is thought this type of apnea is a result of moderately to severely impaired cardiac function and is possibly indicative of high mortality. Treatment of CSA-CSR is best undertaken by treating the underlying cardiac condition which may include with medications, pacemakers, transplantation or continuous positive airway pressure (CPAP). In such patients CPAP exerts unique effects to assist cardiac function and reduce pulmonary edema. Whether CPAP improves survival in this heart failure population remains to be determined.
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PMID:Sleep in heart failure. 1911 Jan 35

Sleep-related breathing disorders are common adult illnesses in Western countries and classified as either dominant obstructive sleep apnoea or dominant central sleep apnoea. Cheyne-Stokes Respiration is part of the spectrum of CSA. The earliest descriptions of patients who presumably suffered from sleep apnoea were made in the 19th century. The term ''Pickwickian'' in connection with sleepy patients was introduced in 1889. The first electrophysiological sleep recordings of Pickwickian patients and the understanding of the syndrome as disordered breathing in sleep, were made during the late 1950s and 1960s at the universities of Heidelberg and Freiburg in Germany. The term sleep apnoea syndrome was introduced by Guilleminault from Stanford. The introduction of continuous positive airway pressure (CPAP) therapy by C. E. Sullivan and co-workers gave an enormous impetus to the field of sleep-disordered breathing. Its recognition as a public health problem was facilitated by the Wisconsin study, investigating the prevalence of sleep apnoea in the middle-aged general population. Nowadays obstructive sleep apnoea (OSA) is recognised as an independent risk factor for a wide range of clinical conditions, such as atherosclerosis, hypertension, heart failure, arrhythmias, stroke, diabetes, and depression. This article focuses on issues related to OSA and CSA/CSR, their pathogenesis, interaction with other comorbidities including cardiovascular diseases. Future research will focus on treatment effects on cardiovascular and metabolic outcomes in sleep apnoea and on the pathophysiological mechanisms responsible for the inflammatory state and cardiovascular morbidity in the syndrome. Other potential areas of research include biochemical markers, new diagnostic and therapeutic modalities.
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PMID:[Sleep-related breathing disorders - historical development, current status, future prospects]. 2082 43

Cockayne is a segmental progeroid syndrome that has autosomal recessive inheritance pattern. It is mainly characterized by Intrauterine growth retardation, severe postnatal growth deficiency, cachectic dwarfism, microcephaly, wizened face, sensorineural hearing loss, cataracts, dental caries, cardiac arrhythmias, hypertension, atherosclerosis, proteinuria, micropenis, renal failure, skeletal abnormalities, skin photosensitivity, decreased subcutaneous adipose tissue, cerebral atrophy, dementia, basal ganglia calcifications, ataxia and apraxia. It has a complex phenotype given by genetic heterogeneity. There are five gene responsible for this syndrome: CSA, CSB, XPB, XPD and XPG, in which various mutations have been found. The biochemical effect of these mutations includes dysfunctional protein of the repair system for oxidative damage to DNA, the complex coupled to transcription and the nucleotide excision repair system. Considering the role played for these proteins and its effects on clinical phenotype when they are deficient, we suggest that these genes might be candidates for analyzing susceptibility to common chronic degenerative diseases related to oxidative stress and aging.
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PMID:[The metabolic and molecular bases of Cockayne syndrome]. 2141 36

Sleep apnea is frequently observed in patients with heart failure (HF). In general, sleep apnea consists of two types: obstructive and central sleep apnea (OSA and CSA, respectively). OSA results from upper airway collapse, whereas CSA arises from reductions in central respiratory drive. In patients with OSA, blood pressure is frequently elevated as a result of sympathetic nervous system overactivation. The generation of exaggerated negative intrathoracic pressure during obstructive apneas further increases left ventricular (LV) afterload, reduces cardiac output, and may promote the progression of HF. Intermittent hypoxia and post-apneic reoxygenation cause vascular endothelial damage and possibly atherosclerosis and consequently coronary artery disease and ischemic cardiomyopathy. CSA is also characterized by apnea, hypoxia, and increased sympathetic nervous activity and, when present in HF, is associated with increased risk of death. In patients with HF, abolition of coexisting OSA by continuous positive airway pressure (CPAP) improves LV function and may contribute to the improvement of long-term outcomes. Although treatment options of CSA vary compared with OSA treatment, CPAP and other types of positive airway ventilation improve LV function and may be a promising adjunctive therapy for HF patients with CSA. Since HF remains one of the major causes of mortality in the industrialized countries, the significance of identifying and managing sleep apnea should be more emphasized to prevent the development or progression of HF.
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PMID:Sleep apnea and heart failure. 2282 95


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