ISSN:0272-4391    

DOI:10.1002/ddr.430060202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

摘要:

AbstractAtherosclerosis is a generalized disease of the arterial system that develops slowly and is symptomless until lesions have become sufficiently large and complicated to cause ischemia. The personal and economic costs of atherosclerosis are enormous. There is a consensus among experts and data from recent long‐term studies to indicate that reduction in the primary risk factors (elevated plasma cholesterol, elevated blood pressure, and smoking) leads to effective management of asymptomatic individuals at risk. Research has also led to an understanding of cholesterol metabolism and clearance pathways from some tissues. However, the factors regulating cholesterol influx and efflux from the arterial wall are currently poorly understood. The role of the monocyte/macrophage in the genesis of the atherosclerotic lesion is receiving renewed attention. The secretory products of the macrophage contain proteases and growth factors capable of causing tissue destruction and cell proliferation, two important components of advanced lesions. Recent advances in cell culture technique have allowed the in vitro growth and/or passage of all the cell types implicated in the development of the lesion. The efficacy of antiatherosclerotic agents must ultimately be proven in man. However, a battery of animal models has been developed over a period of 30 years, which when used appropriately might predict the utility of a drug in ma

ISSN:0272-4391    

DOI:10.1002/ddr.430060203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

摘要:

AbstractTitle: New perspectives for the clinical evaluation of atherosclerosis. Atherosclerosis is a progressive and degenerative disease of the artery wall that begins relatively early in life but does not become recognized until it is severe enough to result in the development of clinical signs and symptoms. Too often, however, these clinical events are closely associated with morbidity and mortality. Much progress has been made in elucidating those risk factors associated with development of clinical endpoints; however,riskwhen used in this context is defined as increased chance and, except in unusual circumstances, cannot predict specific individuals who will develop signs and symptoms nor when these events will occur. Several methods have been developed during the last 25 years that have the potential for detecting atherosclerotic plaques in their preclinical stages. High‐resolution, B‐mode ultrasound imaging, particularly, has high sensitivity and specificity in detecting carotid artery plaques and in accurately measuring size characteristics of individual lesions. Reliability studies have demonstrated the possibility of detecting changes in asymptomatic carotid artery atherosclerosis with 95%percnt; confidence, if these changes are greater than ± 0.4 mm. Application of this noninvasive method to identify subjects with asymptomatic lesions, and to monitor plaque changes over time, will aid greatly in determining the efficacy of various therapies and potentially will decrease the mortality and morbidity associated with st

ISSN:0272-4391    

DOI:10.1002/ddr.430060204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

摘要:

AbstractThe effects of calcium antagonists on mobilization of calcium stores critical for induction and development of atherosclerosis are only beginning to be delineated. The idea that these types of agents (by selectively altering either platelet function or smooth muscle proliferation and accumulation of lipids and calcium) can arrest or even reverse the course of atherosclerosis presents an attractive approach. Available experimental information on the actions of calcium antagonists in atherosclerosis is suggestive rather than definitive in this regard. A number of calcium‐sensitive steps in platelet aggregation and secretion as well as in smooth muscle accumulation and deposition of calcium are identified. Related experimental findings in models of arteriosclerosis and hypertension also support the concept that blockade of calcium accumulation in vascular smooth muscle can retard or prevent subsequent interactions leading to enhanced disease states. Thus technical approaches to delineation of the actions of calcium antagonists are available, and, though the therapeutic value of these types of agents is not established, their potential as novel antiatherosclerotic agents is attractiv

ISSN:0272-4391    

DOI:10.1002/ddr.430060205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

摘要:

AbstractExtensive investigation over the past 2 decades has led to a far better understanding of the role of lipoproteins in the etiology and progression of atherosclerosis. Paramount to this understanding has been the elucidation of how cells recognize these macromolecular complexes and metabolize the lipids and proteins they transport. Because of their elevation in plasma of many individuals with premature coronary heart disease, low‐density lipoproteins (LDL) have received particular attention. As primary transporters of cholesterol to cells in mammalian tissues, LDL particles are removed from blood via specific cell surface receptors that facilitate their uptake. Once internalized and exposed to lysosomal enzymes, LDL particles are degraded, “freeing” their cholesterol to regulate cellular cholesterol synthesis and modulate the number of LDL receptors on the cell membrane. This high‐affinity, high‐capacity process has been termed the LDL receptor pathway and is functional in most tissues of the body, especially in liver where over 50%percnt; of the total body LDL degradation occurs. Liver is the target organ of bile acid sequestrants (cholestyramine/colestipol) and HMG‐CoA reductase inhibitors (compactin/mevinolin), both of which induce increased expression of LDL receptors by affecting hepatic cholesterol availability. Unlike liver, the arterial wall under normal conditions is not very active at degrading LDL via the classical LDL receptor pathway. However, when hypercholesterolemia occurs, especially when there is an LDL‐receptor deficiency, the arterial wall removes 20‐‐fold more LDL than normal and with a greater fractional catabolic rate. Thus other endocytotic pathways exist by which LDL can enter cells of the arterial wall. These pathways are not as actuely regulated as the classical LDL receptor pathway, and, as a result, the arterial wall cells, particularly smooth muscle cells and resident macrophages, accumulate cholesteryl esters. In this brief review, the importance of these receptors to the etiology and progression of atherosclerosis is discussed in detail and sites of possible pharmacological interventi

ISSN:0272-4391    

DOI:10.1002/ddr.430060206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

摘要:

AbstractThe metabolism of various lipoproteins is largely regulated by the protein constituents, the apolipoproteins. Although approximately a dozen apolipoproteins have been identified, apolipoproteins B and E (apoB, apoE) appear to play the major role in the receptormediated clearance of lipoproteins by the liver and other tissues, thereby directly influencing plasma lipid levels. In man, apoB is synthesized by both the intestine (apoB‐48) and the liver (apoB‐100), but it is the hepatogenic peptide that is the sole constituent of plasma low‐density lipoproteins (LDL) recognized by the LDL receptor in liver and other tissues. ApoB‐100 is found in normal and atherosclerotic aorta and taken up by aortic endothelium in vivo, providing further evidence that LDL is the source of arterial foam cell lipids. Evidence is provided suggesting that the clinical measurement of plasma apoB‐100 provides a better index than LDL for determining coronary heart disease risk. ApoE, on the other hand, is clearly the most important binding ligand for the hepatic removal of a variety of lipoproteins. Numerous studies suggest that apoE directs peripheral cell cholesterol to the liver for excretion from the body (reverse cholesterol transport). Human apoE can be separated into three major isoforms, which differ in primary structure. Patients with the genetic disorder type III hyperlipoproteinemia have severe atherosclerosis due to an excess of one apoE isoform that does not bind normally to hepatic receptors. Other alterations of apoE can change its conformation and hence its ability to be recognized. Future directions in the treatment of dyslipidemias should include the discovery of pharmacologic agents that facilitate lipoprotein clearance by altering apoE conformation or recognition of apoB‐containing lipoproteins. The control of apoB and apoE synthesis should also provide insights for drug discovery in light of the undisputed roles of these proteins in lipid transport and athe

ISSN:0272-4391    

DOI:10.1002/ddr.430060207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

摘要:

AbstractAthersclerosis is characterized by progressive arterial stenosis of the major vessels of the systemic circulation. In man, atherosclerotic lesions are composed principally of smooth muscle cells, connective matrix derived from these cells, and variable amounts of lipid. Emphasized is the role of the platelet mitogen, platelet‐derived growth factor (PDGF), as a potent stimulus for the proliferation of smooth muscle cells in the development of atherosclerotic lesions. Animal models of proliferative atherosclerosis are reviewed, as are published references of approaches to inhibit smooth muscle cell hyperplasia in these models by drug administration. The results are discussed in terms of the potential therapeutic application of antiproliferative drugs designed to inhibit the mitogenic role of PDGF as a contributory factor in atherogenesi

ISSN:0272-4391    

DOI:10.1002/ddr.430060208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430060201

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1985

数据来源: WILEY