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

Animal models of arterial injury have failed to predict effective therapy to prevent restenosis in humans. While this may relate to species differences in the control of smooth muscle cell growth, many studies have used nonatherosclerotic animals, thereby failing to consider the importance of atherosclerosis in the response to injury. In an attempt to model human restenosis more accurately, we characterized the response to angioplasty in atherosclerotic monkeys. Twenty-one cynomolgus monkeys were fed an atherogenic diet for 36 months (plasma cholesterol, 12 +/- 1 mmol/L [470 +/- 23 mg/dL]). Angioplasty was then performed in the left iliac artery. After 4, 7, 14, or 28 days, bromodeoxyuridine was given to label proliferating cells, and iliac arteries were fixed in situ at physiological pressure (5 or 6 animals at each time point). Comparisons were made between injured and uninjured iliac arteries within each animal. Angioplasty often fractured the intimal plaque and media, transiently increasing lumen caliber (4 days: lumen area, 232.5 +/- 80.3% of control) and artery size as reflected by external elastic lamina area (EEL). EEL and lumen caliber returned to baseline by 7 days. Proliferation was increased throughout the artery wall at 4 and 7 days and later declined to control rates (4 days, injured versus uninjured: adventitia, 45.0 +/- 6.2% versus 16.3 +/- 7.2%; media, 8.6 +/- 2.6% versus 0.6 +/- 0.1%; intima, 16.0 +/- 5.6% versus 7.8 +/- 3.1%). The intima thickened markedly from 14 to 28 days, but an increase in EEL generally prevented further loss of the short-term gain in lumen caliber (28 days, percent of control: intimal area, 342.8 +/- 88.9%; EEL area, 150.2 +/- 28.9%; lumen area, 119.3 +/- 21.3%). The response to angioplasty in atherosclerotic monkeys appears to closely resemble that in humans. Plaque fracture, delayed recoil, intimal hyperplasia, and remodeling may each be important in determining late lumen caliber. This primate model should prove valuable in defining cellular and biochemical mediators of human restenosis.
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PMID:Time course of cellular proliferation, intimal hyperplasia, and remodeling following angioplasty in monkeys with established atherosclerosis. A nonhuman primate model of restenosis. 854 23

The aim of the present investigation was to examine the occurrence of ultrasound-assessed morphological changes in the right common femoral artery and relate these findings to the ankle-arm index and to symptoms of lower-extremity arterial disease in hypertensive men at high cardiovascular risk (n = 143). Comparisons were made with a healthy reference group consisting of age-matched men at low risk (n = 46). The results showed that it was possible to obtain high-quality measurements of intima-media thickness in about 80% of all men and that the intraobserver variability was satisfactory (14%). A normal mean intima-media thickness was defined, using data from the low-risk group. Plaque occurrence and mean intima-media thickness in the right common femoral artery were significantly associated with ankle-arm index both in the right and left leg. There were more and larger plaques, as well as thicker mean and maximum intima-media complexes, in the high-risk group than in the low-risk group. In the high-risk group, 11% suffered from symptoms of right lower-extremity artery disease, 20% had an ankle-arm index < or= 0.9, 62% had moderate or large plaques (compared with 28% in the low-risk group, P < .001), and 77% had an enlarged intima-media complex. The cumulative frequency of signs of atherosclerosis in the right leg was 81% among the 110 patients in whom complete results from all examinations were available. Our conclusion is that ultrasound measurement of the intima-media thickness of the common femoral artery is a valuable method to evaluate morphological changes related to atherosclerotic disease in the lower extremity.
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PMID:Atherosclerotic disease in the femoral artery in hypertensive patients at high cardiovascular risk. The value of ultrasonographic assessment of intima-media thickness and plaque occurrence. Risk Intervention Study (RIS) Group. 869 61

Three consecutive periods in the natural history of atherosclerosis are amenable to medical treatment. Plaque development is the main target of prevention, which also aims at slowing the progression of already existing plaques. The control of several established risk factors (high blood cholesterol, high blood pressure, diabetes mellitus, tobacco smoking) has already yielded encouraging benefits, especially in the field of secondary prevention. More efficient prophylaxis is to be expected, either from the further improved control of these classic risk factors with earlier, stronger, and longer interventions or from the correction of newly established causal determinants of atherosclerosis. A plaque manifests itself clinically through progressive or abrupt obstruction of the arterial lumen, which can be avoided or retarded by interventions aimed at reducing thrombosis, at controlling plaque instability (the major cause of thrombosis), and at enhancing arterial remodeling (which allows compensatory enlargement of the arterial lumen). When ischemia has occurred, a third wave of palliative treatments aims at improving energy supply to the organ with compromised vascularization. Classic treatments reduce oxygen consumption or improve oxygen extraction by ischemic tissues. In addition, the design of drugs to enhance the development of collateral channels appears to be promising therapeutic approach.
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PMID:Pharmacologic approaches to the treatment of atherosclerotic arterial obstruction. 869 60

For longitudinal studies on atherosclerosis and restenosis after angioplasty by intravascular ultrasound (IVUS), it is essential that repeated studies are performed at exactly the same location along an arterial section. In human femoral arteries, lumen and plaque area functions of two subsequent IVUS pullback maneuvers were compared by cross-correlation analysis. In cross-correlation analysis of two functions with equal abscissa values, the data sets are repetitively correlated after incremental shifts of the two functions along the abscissa. This results in multiple correlation coefficients with a maximum at the relative position where the two functions show the closest match. In group A (12 patients), both pullbacks were performed after angioplasty and in group B (17 patients) one pullback was performed before angioplasty and the second immediately after angioplasty. In group A, cross-correlation showed a shift between lumen area functions of 5 mm in one patient and no shift in the other patients. Maximum correlation coefficients in group A ranged from 0.644 to 0.978. Four patients from group B showed shifts from 2.5 to 35 mm. Maximum coefficients were significantly smaller than in group A: 0.259-0.864 (p < 0.01). Plaque area functions in group B showed higher correlations (0.468-0.862, p = 0.034) and only two shifts. Cross-correlation of lumen and plaque area functions may be used to compute location shifts between two subsequent IVUS registrations and to correct such shifts.
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PMID:Computation of a location shift between two subsequent intra vascular ultrasound registrations by cross-correlation analysis of the lumen area functions. 873 33

Compensatory arterial enlargement in response to atherosclerosis has been demonstrated for the left main coronary artery. Only limited data is available on the interaction of patient characteristics and atherosclerosis with coronary artery dimensions. The purpose of the present study was to evaluate the influence of age, race, body habitus, heart weight and atherosclerosis on coronary artery dimensions of young males. Hearts from 137 young men (age 32 +/- 8 years; 78 black, 59 white) with unnatural deaths (homicide, suicide, accident, drug overdose) were perfusion-fixed, and histologic sections were obtained from the left main, proximal left anterior descending and left circumflex coronary arteries. Computerized planimetry was performed on Movat stained sections. Multiple regression analysis was used to evaluate the relative contribution of plaque size, age, race, heart weight and body surface area on coronary dimensions and compensatory enlargement in response to atherosclerosis. In the left anterior descending and left main coronary arteries, black race, body surface area and age were independent predictors of increased lumen area. In the left circumflex, age was a predictor of lumen area. Plaque area, black race and body surface area independently predicted increased area enclosed by the internal elastic lamina area. There was compensatory enlargement of internal elastic lamina with increasing plaque size in both races in the three arteries, but the percent luminal stenosis was greater in whites due to smaller artery size. Luminal narrowing did not develop until plaques occupied 30% of internal elastic lamina area. Among a population of young men with non-cardiac deaths, blacks have larger lumen and area enclosed by internal elastic lamina than whites. Age and body surface area are major determinants of lumen areas, and compensatory arterial enlargement was seen in all examined arteries in the present study.
Atherosclerosis 1996 Jun
PMID:Effect of age, race, body surface area, heart weight and atherosclerosis on coronary artery dimensions in young males. 878 55

Recurrence of atherosclerotic plaque growth after interventional therapy, restenosis, is a significant clinical problem occurring in 20%-50% of cases. We have developed a new avian model for the investigation of restenosis after arterial injury in cholesterol fed White Leghorn roosters. Atherosclerotic plaque growth 1-30 weeks after angioplasty balloon mediated endothelial injury in the abdominal aorta was studied in 37 roosters. Roosters were maintained on either normal poultry diet or high cholesterol diet. Twelve cholesterol fed roosters were also fed a hormone supplemented diet in order to modify plaque morphology. The procedural success rate was high. Angiographic stenoses (mean 36% with maximum of 74%) were detectable in cholesterol fed roosters after balloon angioplasty with associated histological evidence of plaque growth (P < 0.017). Cholesterol feeding enhanced fatty plaque growth; hormone manipulation increased calcific and ulcerated plaque but with high associated morbidity. Three interventional devices were subsequently examined in 32 roosters (16 laser angioplasty, 7 atherectomy, and 9 stent implant). Plaque development was again assessed by contrast angiography and histological analysis. We conclude that balloon mediated arterial injury in cholesterol fed roosters produces early proliferative and late, complex atherosclerotic lesions providing an inexpensive model for plaque development after intimal injury.
Atherosclerosis 1996 Jan 05
PMID:Development of an avian model for restenosis. 892 54

Three-dimensional (3D) ultrasound angiography was performed to diagnose carotid artery atherosclerosis. Thirty-five patients (15 women, 20 men) with a history of cerebrovascular disease were examined using conventional color-coded Doppler ultrasound and 3D ultrasound angiography. Carotid stenosis was initially diagnosed using continuous-wave Doppler ultrasound. To determine intraobserver and interobserver reliabilities, 21 patients were evaluated using 3D ultrasound on three occasions. Sixty-five percent of patients were diagnosed with stenosis of more than 50%. Twenty-two percent of plaques had a smooth surface, 72.9% were ulcerated, and 5.1% were indeterminate. Data collection for 3D imaging required 5 minutes per patient, whereas image processing and plaque volume quantification required 30 minutes. Plaque volume ranged from 0.053 to 0.685 ml. The intraobserver and interobserver variabilities were 4.16 and 5.87%, respectively (r = 0.96, p < 0.0001; r = 0.89, p < 0.0001). 3D Color Doppler and 3D ultrasound angiography assessments of plaque volume differed by 8.5%. Plaques were more precisely differentiated using 3D ultrasound, and plaque volume quantification was less affected by echo shadowing after 3D reconstruction. In comparison to other techniques for the quantification of atherosclerotic lesions. 3D ultrasound angiography offers a more precise quantitative method for prospective, clinical studies of atherosclerosis.
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PMID:Three-dimensional ultrasound angiography (power mode) for the quantification of carotid artery atherosclerosis. 903 31

The aim of this study was to evaluate the cholesterol-lowering and antiatherosclerotic effect of the HMG-CoA reductase inhibitor pravastatin sodium at a dosage comparable to human therapy. Twelve heterozygous WHHL rabbits (13 months old) were fed 100 g per day of a low cholesterol (0.03%) enriched diet for 12 months. Six of these animals also received pravastatin sodium at a daily dose of 1 mg/kg body weight (verum group). In the verum group, total plasma cholesterol levels were lower by 47%(P < 0.05) and relative aortic plaque volume (% ratio of total plaque volume to the aortic lumen) was reduced by 78% (P < 0.05), when compared to the control group. Plaque composition was analysed at 30 cross-sectional levels of the entire aortic wall using a grid window. Compared to the control group, the plaque type, in terms of architecture and composition, was altered as follows: lesions in the verum group had no confluent atheromatous cores and showed a pattern of a diffuse mixture of the main plaque components with a decreased relative content of necrosis (-44%) and an increased relative content of smooth muscle cells (+19%), whereas the relative content of macrophage-derived foam cells and collagen were nearly unaffected. Furthermore, a similar plaque volume and type was observed in animals with comparable cholesterol profiles. There was no histologic evidence for structurally damaging effects of pravastatin sodium on the arterial wall. We conclude that pravastatin sodium reduces total plasma cholesterol levels in this animal model, thereby leading to smaller plaques and a different plaque type.
Atherosclerosis 1997 Feb 10
PMID:Effects of low-dose pravastatin sodium on plasma cholesterol levels and aortic atherosclerosis of heterozygous WHHL rabbits fed a low cholesterol (0.03%) enriched diet for one year. 905 Jul 70

Coronary plaque inflammation may promote plaque rupture and thrombosis. To test this hypothesis, 351 coronary plaques from 83 patients were formalin-fixed and stained with haematoxylin and eosin. There were six groups: (1) ruptured plaques; (2) intact plaques from recently infarcted hearts; (3) plaques from hearts with severe coronary atherosclerosis without identifiable thrombosis; (4) native explanted hearts with severe coronary atherosclerosis; (5) cardiac transplant atherosclerosis; and (6) fatalities unrelated to coronary atherosclerosis. Selected arteries were immunostained for leukocyte markers and serially sectioned to identify plaque rupture. There were infiltrates of CD68-positive macrophages and CD3- and CD8-positive T cells adjacent to all plaque ruptures. Labelling with HLA-DR and CD30 indicated inflammatory cell activation. Plaque rupture was strongly statistically associated with the severity and frequency of superficial plaque inflammation but not that of deep plaque inflammation. Although atherosclerotic inflammation has been identified adjacent to rupture, this is its first comparison with control plaques. These results support the concept that inflammation in the fibrous cap is particularly associated with plaque rupture.
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PMID:Association of coronary plaque rupture and atherosclerotic inflammation. 907 9

Atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the potentially lethal acute coronary syndromes. Plaques with a large extracellular lipid-rich core, thin fibrous cap with reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells appear to be most vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses, resulting from biomechanical and hemodynamic forces acting on plaques, are concentrated. Reduced matrix synthesis as well as increased matrix degradation may predispose fibrous caps to rupture spontaneously or in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization resulting in reduction of the frequency of acute coronary syndromes. This putative concept of plaque stabilization, although attractive, has not yet been rigorously validated in humans. Indirect data from clinical trials involving lipid lowering/modification and lifestyle/risk factor modification, however, provide strong support for this new paradigm. Thus, plaque stabilization may prove to be an important modality for reduction of lethal consequences of coronary atherosclerosis.
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PMID:Pathophysiology of plaque rupture and the concept of plaque stabilization. 907 89


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