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M G Bond

Publications and source records attributed to M G Bond.

At least 55 records · Page 3Linked to original sources
PubMed1993

Sonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack.

Doppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA.

Aged↗
PubMed1993

Ultrasonic-pathological comparison of the human arterial wall. Verification of intima-media thickness.

Recent intravascular ultrasound experience challenges the accuracy of ultrasonic measurement of arterial wall thickness. We reevaluated the correlation between histological and sonographic measurements of intima-media thickness using standard transcutaneous vascular technology. Carotid and femoral arterial segments were imaged before and after fixation using a 7-MHz linear-array vascular transducer. Log compression and beam orientation were varied. Mean intima, media, and adventitia thicknesses were measured and compared with corresponding histological tunica. Tissue processing caused 2.5% shrinkage. Intraobserver reading error was 0.7% for histology and 5.4% for sonography. Ultrasound overestimated the thickness of the intima and adventitia and underestimated the thickness of the media. For combined intima-media thickness, the differences between histology and imaging were insignificant, averaging 4% for the carotid artery and 9% for the femoral artery in the far-wall projection. In the near-wall projection, sonographic intima-media thickness was 20% less than that determined histologically. We conclude that ultrasonography is limited mainly by axial resolution in quantifying the dimensions of individual arterial tunica but is capable of accurately measuring far-wall intima-media thickness.

Aged↗
PubMed1992

The human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane.

The chick chorioallantoic membrane was used to determine whether the carotid atherosclerotic plaque stimulates angiogenesis. Carotid endarterectomy specimens (1 mm3) with fibromuscular plaque (n = 8) and complicated plaque (n = 11) were implanted on the membrane on day nine of incubation and the response evaluated on day 11. Following fixation in situ with 10% formalin the angiogenic response was evaluated by: (1) examining whole membrane mounts, (2) quantitatively from a vascular density index and (3) from a histological study. Unmanipulated chorioallantoic membrane (n = 11) and plaque boiled prior to implantation (n = 6) served as controls. The vascularity of whole mounts of both fibromuscular and complicated plaque was greater than the controls. Vessel density of the membrane was estimated by counting the number of vessels intersecting four concentric circles (144.5 mm total circumference) placed on the formalin fixed membrane. The vascular density index due to the fibromuscular plaque (390.6 +/- 8.3) and complicated plaque (391.0 +/- 14.9) were similar (P greater than 0.9) but were significantly greater (P less than 0.001) than the unmanipulated membrane (327.9 +/- 5.6) or after treatment with the boiled plaque (283.8 +/- 15.6). Transforming growth factor beta 1 confirmed the validity of the experimental model to study angiogenesis. The histology of the chorioallantoic membrane due to either type of plaque was similar. Numerous vessels surrounded the plaque, and intraplaque vessels containing nucleated chick erythrocytes were observed. Although scattered vessels surrounded the boiled plaque, intraplaque vessels were not observed. This study demonstrates that the atherosclerotic plaque has angiogenic properties that may account for the increase in vasa vasorum that is associated with the plaque.

Allantois↗
PubMed1992

Pravastatin, lipids, and atherosclerosis in the carotid arteries: design features of a clinical trial with carotid atherosclerosis outcome.

The Pravastatin, Lipids, and Atherosclerosis in the Carotids trial (PLAC-II) was initiated in 1987 and is the first double-masked randomized clinical trial with progression of early extracranial carotid atherosclerosis as an outcome variable. The trial will compare a lipid-lowering agent (pravastatin, a hydroxymethylglutaryl CoA reductase inhibitor) with placebo for ability to retard the rate of progression of extracranial carotid atherosclerosis over 3 years. Inclusion criteria consisted of prevalent coronary artery disease, moderately elevated low-density lipoprotein (LDL) cholesterol (between the 60th and 90th percentiles), and the presence of at least one extracranial carotid artery atherosclerotic plaque that had an intimal-medial thickness (IMT) > or = 1.3 mm as visualized by B-mode ultrasound. Of approximately 650 patients who qualified on the basis of coronary disease and elevated LDL cholesterol, 55% were excluded because of B-mode criteria. One hundred and fifty-one males and females 50-75 years of age were recruited. Random allocation produced placebo-treated and test-treated groups that were similar for baseline historical data, physical findings, laboratory tests, lipid values, and B-mode characteristics. Baseline concentrations of plasma total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol were 234, 166, and 41 mg/dl, respectively. Baseline plasma concentration of triglyceride was 170 mg/dl. Despite selection of participants whose arteries, overall, were suitable for the trial, individual segments in some participants could not be visualized. Ninety-seven percent of the individual carotid artery segments were visualized in the common carotid, 88% in the bifurcation, and 63% in the internal carotid artery. Far walls were slightly more often visualized than near walls, and nonvisualization was most common for the near wall of the internal carotid. Nonvisualized segments were comparable between both treatment groups. The distribution of arterial walls with qualifying plaque of > or = 1.3 mm IMT was similar for the two groups, and the two groups were also comparable for the primary outcome determinant, mean maximum IMT (mean of maximum of all visualizable sites, 1.32 mm for each treatment group). There are special problems related to recruitment and evaluation of patients for a clinical trial such as this, but the atherosclerosis outcome measurement markedly enhances power and compensates for difficulty in recruitment.

Aged↗
PubMed1992

Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group.

BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years. METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.

Aged↗
PubMed1992

Postprandial triglyceridemia and carotid atherosclerosis in middle-aged subjects.

BACKGROUND AND PURPOSE: It has been suggested that a postprandial accumulation of triglyceride-rich lipoproteins promotes the development of atherosclerosis. This study was designed to test the hypothesis that postprandial lipemia is independently associated with intima-media thickening of the extracranial carotid arteries. METHODS: Forty-seven middle-aged, moderately hypercholesterolemic individuals were recruited for a 1-day study of the lipemic response to a standard high-fat test meal. The formula was fed at a dose of 65 g fat/m2 body surface area, after a 14-hour fast, and blood was obtained for triglyceride analysis hourly for 8 hours. A baseline lipid profile was obtained. Each subject underwent a carotid ultrasound examination. The extent of alimentary lipemia (peak triglyceride response) was correlated with the carotid artery wall thickness as measured by B-mode ultrasound. RESULTS: Univariate analyses indicated an inverse correlation between peak triglyceride response and high density lipoprotein cholesterol concentration and a direct correlation with male sex, baseline triglyceride concentration, background fat intake, and waist-to-hip ratio. Of these, the only variable that showed a univariate correlation with B-mode score was peak triglyceride response. Age and cigarette smoking were also correlated with B-mode score in univariate analyses. The correlation coefficient (r = 0.52) between peak triglyceride response to a fat-rich meal and B-mode score was significant (p less than 0.002) and remained so in multivariate analysis. Forward-selection stepwise regression resulted in the inclusion of only peak triglyceride response (p = 0.001) and smoking history (p = 0.005) as important predictors of carotid wall thickness in a linear model. CONCLUSIONS: The association between lipemic response and carotid wall thickness suggests that prolonged exposure of arterial wall cells to triglyceride-rich chylomicron remnants enhances the atherogenic process.

Carotid Arteries↗
PubMed1992

Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study.

BACKGROUND AND PURPOSE: To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study. METHODS: Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility. RESULTS: The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small. CONCLUSIONS: The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.

Adult↗
PubMed1992

MIDAS: hypertension and atherosclerosis. A trial of the effects of antihypertensive drug treatment on atherosclerosis. MIDAS Research Group.

Although clinical trials of the efficacy of antihypertensive treatment have demonstrated impressive reductions in the incidence of stroke, the reduction in coronary artery disease mortality has been less impressive. It may be that the antihypertensive drugs used in these trials induced metabolic disturbances, or produced inadequate regression of left ventricular hypertrophy, thus blunting the reduction in risk of coronary artery disease expected with blood pressure-lowering. Isradipine, a dihydropyridine calcium antagonist known to be an effective antihypertensive agent, has also displayed pronounced antiatherogenic effects in animals. Thus, a reasonable hypothesis could be that isradipine not only reduces the level of blood pressure, but also may have a positive effect on the evolution of atherosclerotic plaque in coronary and carotid arteries, thereby leading to prevention of clinical sequelae of atherosclerosis. On this basis, a 3-year clinical trial is being carried out in the United States--the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS)--to establish the efficacy of isradipine in inhibiting atherogenesis and retarding the progression of atherosclerosis in carotid arteries of hypertensive patients. The primary end point of the study is intima-media thickness and the extent of atherosclerotic plaque in the carotid arteries, as measured by B-mode ultrasonography.

Antihypertensive Agents↗
PubMed1991

Irradiation. A significant risk factor for carotid atherosclerosis.

Radiation exacerbates the development of atherosclerosis in the large arteries of animals and is postulated to do likewise in human beings. To study this relationship, we used high-resolution B-mode ultrasonography to measure carotid artery wall thickness in 29 previously irradiated head and neck cancer patients and compared the results with those of nine epidemiologically similar but nonirradiated head and neck cancer patients. Maximal intima-media thickness was greater in the study group (mean, 1.28 +/- SE 0.06 mm) than in the control group (mean, 0.90 +/- SE 0.05 mm). Even after the effects of age, hypertension, and tobacco consumption were controlled, these differences remained statistically significant. This study suggests that irradiation may contribute to the development of more severe and extensive carotid atherosclerosis in head and neck cancer patients who receive radiation therapy.

Adult↗
PubMed1991

Anatomic correlates of aortic pulse wave velocity and carotid artery elasticity during atherosclerosis progression and regression in monkeys.

We noninvasively measured changes in average aortic stiffness in 79 cynomolgus monkeys being fed cholesterol progression, regression, and control diets by measuring pulse wave velocity (PWV) in 260 experiments during a 30-month period. Every 6 months, a group of monkeys was studied with invasive aortic PWV techniques and with ultrasonically determined pressure-strain elastic modulus (Ep) of the carotid artery, and then the group was killed so that morphometric evaluation of atherosclerosis severity could be made. After 6 months of a cholesterol progression diet, PWV decreased slightly from 6.2 +/- 0.1 to 5.7 +/- 0.1 m/sec, followed by an approximate linear increase to 8.8 +/- 1.2 m/sec after 30 months on the diet. The corresponding ratio of intimal (plaque) area to medial area (IA/MA) measured on perfusion-fixed cross-sections of the abdominal and thoracic aortas increased from 0.16 +/- 0.07 at 6 months to 1.23 +/- 0.22 at 30 months. Monkeys in the regression groups were fed the cholesterol progression diet for 18 months, followed by a chow diet for 6 or 12 months. In the first 6 months of the cholesterol regression diet, PWV continued to increase from 7.0 +/- 0.2 to 8.1 +/- 0.4 m/sec, and IA/MA was 1.24 +/- 0.18. However, after 12 months of the cholesterol regression diet, PWV decreased to 6.8 +/- 0.4 m/sec, and IA/MA was 0.90 +/- 0.18. The variability of the data demonstrates that PWV is not a simple function of atherosclerosis severity, and the best simple correlation was r = 0.69 (r2 = 0.48) between PWV and intimal area. However, multiple regression analysis of aortic PWV, systolic (SP) and diastolic (DP) blood pressures, and total plasma cholesterol concentration (TPC), all of which can be measured with minimally invasive techniques, improved the prediction of the IA/MA ratio through the following equation: IA/MA = 0.127 PWV-0.039 DP+0.023SP+0.0003TPC-0.292 (r = 0.81, r2 = 0.66). These data suggest that arterial stiffness in combination with minimally invasive parameters can be used to predict the severity of diffuse asymptomatic atherosclerosis in monkeys. However, more widespread application of these data to humans is uncertain because of biological variability and differences between animal models and human subjects.

Animals↗
PubMed1991

Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group.

Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.

Age Factors↗
PubMed1991

The Multicenter Isradipine/Diuretic Atherosclerosis Study: a study of the antiatherogenic properties of isradipine in hypertensive patients. MIDAS Research Group.

Hypertension is a risk factor for the development of atherosclerosis and its complications, which are among the major causes of morbidity and mortality. Although recent clinical trials indicate that antihypertensive treatment reduces morbidity and mortality associated with stroke, congestive heart failure, and renal insufficiency, questions remain as to whether such treatment also prevents coronary heart disease (CHD) mortality. The observed reduction in CHD mortality from pooled clinical trial data was 10-14% and was much less than the expected 20-25% reduction for a 5-6 mm Hg reduction in diastolic pressure. One explanation may be that subtle adverse metabolic effects of treatment may have blunted the beneficial effects. Isradipine, a dihydropyridine calcium antagonist, is a potent antihypertensive drug with antiatherogenic properties in animal models. Therefore, we hypothesized that isradipine may be appropriate for testing the efficacy of antihypertensive treatment in retarding the progression of atherosclerosis in humans. The Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS) is a clinical trial designed to compare the efficacy of isradipine (2.5 or 5 mg b.i.d.) with hydrochlorothiazide (12.5 or 25 mg b.i.d.) in retarding the progression of early carotid atherosclerosis as monitored by high-resolution B-mode ultrasonography.

Adult↗
PubMed1991

Antiatherogenic properties of calcium antagonists.

Atherosclerosis results from multiple factors, and involves several mechanisms including endothelial monocyte and smooth muscle cell changes, cholesterol accumulation, lumen stenosis, necrosis, mineralization, plaque hemorrhage, rupture, and thromboembolism. Calcium antagonists have been shown in hypercholesterolemic animal models to reduce atherosclerosis. This effect cannot be explained on the basis of changes in blood pressure, therefore suggesting that calcium channel antagonists have a direct effect on arterial wall processes associated with plaque evolution. The antiatherosclerosis properties of calcium antagonists have been tested in human subjects and suggest that these compounds inhibit new lesion development. Recent developments in B-mode ultrasonography allow investigators to detect and monitor atherosclerosis noninvasively. This method is being used in several trials within the U.S. and Europe to evaluate treatment effects on carotid atherosclerosis. Carotid artery disease is associated with transient ischemic attacks, ischemic cerebral infarction, and with risk for coronary artery disease. B-mode ultrasonography is a powerful method for monitoring atherosclerosis progression. The combination of this technology with calcium antagonist treatment will allow evaluation of the efficacy of intervention on the arterial wall during the asymptomatic stages of atherosclerosis evolution.

Animals↗
PubMed1990

Effect of heat shock proteins on survival of isolated aortic cells from normal and atherosclerotic cynomolgus macaques.

Alterations in the level and distribution of arterial heat shock proteins (HSPs) have been demonstrated during atherogenesis. The significance of these changes within the developing and dying plaque, however, is not understood. To examine a potential protective effect of HSPs on arterial cells, enzymatically isolated cells from normal and diet-induced atherosclerotic aortas of cynomolgus macaques were stressed for 20 h with and without added 72/73 kDa heat shock proteins (HSP-72/73), over a range of temperatures and dosages. Cells were analyzed for changes in viability and lysosomal membrane integrity. The responses of cells from normal and diseased aortas for all test regimens were similar. Viability and lysosomal membrane integrity of untreated cells were correlated (r = 0.85), and both factors declined with increasing thermal stress (P less than 0.0005 and P less than 0.004, respectively). Exogenous HSP-72/73 increased cell viability after stress at a minimum concentration of 10 micrograms/ml (P less than 0.05) but was not concentration dependent. Response to different temperatures showed exogenous HSP-72/73 increased cell survival at all temperatures, with the greatest effect at 37 degrees C (P less than 0.01). In contrast, HSP-72/73 did not have an effect on lysosomal membrane integrity for the test period studied. The results demonstrate exogenous HSP-72/73 increases arterial cell survival, suggesting these proteins are associated with a protective mechanism in normal and diseased arteries.

Animals↗
PubMed1990

Correlation of noninvasive arterial compliance with anatomic pathology of atherosclerotic nonhuman primates.

Fifteen cynomolgus monkeys were fed a control (n = 3) or cholesterol-containing diet (n = 12) for 26 months. An impedance plethysmograph and a calibrated volume plethysmograph were used to determine femoral arterial volume change, delta V, from femoral arteries. Abdominal aorta pulse pressure was measured directly. The ratio of delta V to pulse pressure, delta P, defined femoral artery compliance. At necropsy, sections of pressure fixed common iliac, external iliac, femoral and carotid arteries were obtained for measurements. The site of the largest atherosclerotic lesion was chosen for histologic measurement. The percentage intima in arterial tissue (PIAT) was determined at the site of the largest atherosclerotic lesions in iliac arteries and averaged. Peak compliance was inversely correlated with the PIAT (Pearson correlation -0.39, P less than 0.10, n = 21) which improved to r = -0.52, P less than 0.01 (n = 27) when the PIAT also included the carotid atherosclerosis. The correlation coefficients were comparable to those obtained for total plasma cholesterol concentration, and direct systolic and diastolic blood pressure. Peak compliance and alpha-cholesterol concentrations provided the best multiple linear regression fit for the prediction of PIAT.

Animals↗
PubMed1990

Interventional clinical trials using noninvasive ultrasound end points: the Multicenter Isradipine/Diuretic Atherosclerosis Study. The MIDAS Research Group.

Ultrasound has become a well-established method for the clinical evaluation of carotid artery atherosclerosis. In the past few years, high-resolution ultrasound methods have been used more frequently in the study of the natural history of atherosclerosis. Most recently, B-mode ultrasound has enabled investigators to detect and monitor early stages of carotid artery atherosclerosis, when lumen stenosis is between 15 and 45%. Epidemiological studies using high-resolution ultrasonography will allow researchers to correlate traditional risk factors for atherosclerosis with changes over time in lesion incidence, prevalence, and severity. Investigators can also study the effects of drug treatment on the early stages of disease by monitoring rates of lesion progression or regression in carotid arteries. Several large epidemiological and clinical intervention trials are currently underway that use high-resolution B-mode ultrasonography to measure intima-media or total wall thicknesses in extracranial carotid arteries. In these studies, the reproducibility of arterial wall measurements is the most critical factor in establishing rates of lesion progression or regression. This paper describes the ultrasound methods currently being used to determine the effect of the calcium antagonist, isradipine, on patients with asymptomatic carotid artery atherosclerosis.

Arteriosclerosis↗
PubMed1990

Immunohistochemical localization of heat shock protein-70 in normal-appearing and atherosclerotic specimens of human arteries.

Heat shock proteins (HSPs) are synthesized by cells under metabolic stress and are known to enhance a cell's ability to survive life-threatening stress. The authors have begun to examine HSPs in the context of human atherosclerosis. This study demonstrated immunohistochemically the presence of HSP-70 in human and rabbit arteries, and its distribution in relation to necrosis and lipid accumulation, as well as vascular smooth muscle cells and macrophages, in human atherosclerotic plaques. Advanced lesions from 10 human carotid endarterectomy specimens were compared with 11 human aortic specimens from autopsy and 8 rabbit aortas. The immunostaining procedure used a mouse monoclonal antibody specific for the inducible form of HSP-70. Normal rabbit aortas were tested for changes in HSP-70 up to 24 hours after removal, and were used as controls for the human aortas. Representative plaques were examined for lipid content by osmium staining, and for smooth muscle cell and macrophage components using cell-specific monoclonal antibodies followed by immunostaining. The results indicated that HSP-70 was present in human and rabbit arteries and remained unchanged in distribution or concentration up to 15 hours after death. HSP-70 was present weakly throughout the media of normal-appearing arterial specimens. In contrast, HSP-70 was concentrated in the central portions of more thickened atheromas around sites of necrosis and lipid accumulation. Macrophages were coincident with these areas and were observed to be lipid-loaded. In contrast, patches of smooth muscle cells were observed in very complicated plaques, but without consistent association with necrosis or increased HSP-70; plaque smooth muscle cells also were observed to contain lipid. Large, relatively avascular and collagenous areas of plaque also were occasionally positive for HSP-70 staining. The results support the hypothesis that elevated HSPs indicate which plaque cells, particularly macrophages, are more stressed in the depth of atheroma, especially in association with necrosis, and should prompt further investigation of the significance of HSP accumulation to the evolution of atherosclerotic plaques.

Arteries↗