Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravascular ultrasound imaging (IVUS) was performed to elucidate the discrepancy between clinical history and angiographic findings and to measure the diameter and area of the lumen of the normal left coronary artery in 55 patients who presented with chest pain but had normal coronary angiograms. The left coronary artery (LCA) was scanned with a 4.8F, 20 MHz mechanically rotated ultrasound catheter at 413 sites. Atherosclerotic lesions were identified at 72 (17%) sites in 25 patients. The mean (SD) (range) plaque area was 5.55 (3.56) mm2 (2-26 mm2) and it occupied 28.8 (9.6)% (13-70%) of the coronary cross sectional area. Calcification was detected at 24 (33%) atherosclerotic sites in nine patients. The correlation coefficients for the lumen dimensions measured at normal sites by IVUS and by angiography were r = 0.93 (SEE = 0.43) mm for lumen diameter and r = 0.89 (SEE = 4.27) mm2 for lumen area (both p < 0.001). 16 of the 30 patients in whom no atherosclerotic plaques were detected in the LCA lumen by IVUS had no risk factors of coronary artery disease. The cross sectional area of 90 consecutive images of left main coronary artery (LMCA), proximal left anterior descending coronary artery (proximal LAD), and mid LAD was measured in these 16 subjects. The mean (SEM) areas at end diastole were LMCA 17.33 (7.98) mm2; proximal LAD 13.56 (5.85) mm2; mid LAD 9.75 (4.67) mm2. During the cardiac cycle the cross sectional area changed by 10.2 (4.0)% in the LMCA, by 8.3 (4.7)% in the proximal LAD, and by 9.8 (4.0)% in the mid LAD. In 11 patients with plagues the change in cross sectional area in plague segments (5.8(3.1)%) was significantly lower than in the segments from patients without plagues (p < 0.001). Lumen area reached a maximum in early diastole rather than in late diastole. IVUS can imagine atherosclerotic lesions that are angiographically silent; it also provides detailed information about plague characteristics. The variation in coronary cross sectional area during the cardiac cycle should not be ignored during quantitative analysis. Maximum dimensions in normal segments are reached in early diastole. Further studies are needed to clarify the clinical significance of atherosclerosis detected by IVUS in patients presenting with chest pain but normal coronary angiography.
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PMID:Intravascular ultrasound imaging of angiographically normal coronary arteries: a prospective study in vivo. 804 42

Polycyclic aromatic hydrocarbons, cigarette smoke components that induce atherosclerosis in animals, require metabolic biotransformation to electrophilic intermediates to exhibit atherogenic effects. The formation of reactive metabolites depends on both rates of cytochrome P450-catalyzed oxidation and rates of detoxification through conjugation with glutathione. Thus, changes in the activity of glutathione S-transferase in vascular tissue could affect the risk of polycyclic aromatic hydrocarbon-induced atherogenesis. We compared the effects of several exogenous chemicals on levels of glutathione S-transferase in aorta and liver. Male Wistar rats were treated with 3-methylcholanthrene, a polycyclic aromatic hydrocarbon, phenobarbital and butylated hydroxytoluene, an antioxidant known to have anti-atherogenic properties. In control animals, glutathione S-transferase activity was about 20-fold greater in liver than in aorta. Subunit expression was tissue specific. GST-Yp, for example, was the most abundant subunit in aorta but was undetectable in liver. In contrast, GST-Ya was barely detectable in aorta but was abundant in liver. Each of the xenobiotics caused induction of glutathione S-transferase but the extent of induction was greater in liver than in aorta. Phenobarbital, for example, caused 300% induction in liver but only 70% induction in aorta. By western blot analysis, differences in amounts of enzyme subunits corresponded to changes in enzyme activity. Thus, exogenous chemicals differentially regulate levels of glutathione S-transferase in the aorta and liver.
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PMID:Differential induction of glutathione S-transferase in rat aorta versus liver. 820 8

In order to use MR imaging to assess progression or regression of atherosclerosis, one must have an idea of the reproducibility of the imaging and image processing techniques. The ability of dark-blood MRI and semiautomated image processing to reproducibility measure the inner boundary of the carotid arteries was evaluated and compared with results obtained using bright-blood MRA. MRI and MRA images were obtained for two normal and two diseased volunteers six times each over a short period of time (6 months). The carotid bifurcation was used to align slices from different imaging sessions. The area for each vessel (right and left common, internal and external carotid artery) was determined for the six imaging sessions. The standard deviations of each lumen area normalized to the average area were computed for each vessel segment for each volunteer. For the common, internal, and external carotids, the averaged normalized standard deviations for MRI were 8, 12, and 17% and for MRA were 6, 8, and 13%. Lumen sizes obtained by MRI and MRA were found to be not statistically different. Eccentric plaques not seen on MRA were visualized by MRI. In conclusion, dark-blood MRI with semiautomated image processing yields reliable lumen areas that are in agreement with those obtained by MRA.
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PMID:Assessment of the reliability of the determination of carotid artery lumen sizes by quantitative image processing of magnetic resonance angiograms and images. 854 54

Interleukin-1 beta (IL-1 beta) is known to have a number of effects on the different cell types present within coronary arteries. In this study we identified the location and phenotype of cells containing IL-1 beta in human coronary artery specimens from patients suffering from either coronary atherosclerosis or cardiomyopathy and correlated the presence of IL-1 beta with disease severity. Luminal endothelial cells, adventitial vessel wall cells, and macrophages were double labeled immunohistochemically for IL-1 beta protein and a cell type-specific monoclonal antibody for either endothelial cells or macrophages. In situ hybridization was performed to locate the presence of IL-1 beta mRNA within the coronary artery wall. In this study IL-1 beta protein was found to be increased in the adventitial vessel walls of atherosclerotic coronary arteries compared with coronary arteries from nonischemic cardiomyopathic hearts. This increase was directly proportional to the severity of coronary atherosclerosis. IL-1 beta protein was also detected in luminal endothelium and macrophages of atherosclerotic coronary arteries and coronary arteries from nonischemic cardiomyopathic hearts. IL-1 beta mRNA was found in luminal endothelial cells, adventitial vessel endothelial cells, and macrophages. We conclude that IL-1 beta is produced by endothelial cells and macrophages in coronary arteries from ischemic hearts and to a lesser extent from nonischemic cardiomyopathic hearts.
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PMID:Interleukin-1 beta in coronary arteries of patients with ischemic heart disease. 869 38

Endothelin (ET) is a very potent vasoconstrictor peptide, which was originally reported to be produced by endothelial cells and to act locally in a paracrine fashion to regulate vascular tone. Recent studies have demonstrated that endothelin-1 (ET-1) not only is produced by endothelial cells, but is also present in non-endothelial cells of atherosclerotic lesions. The present study was therefore designed to characterize the cell type and distribution of ET-expressing cells in different areas of human atherosclerotic coronary plaques, obtained by directional atherectomy of 30 patients. In addition, ET-1 messenger RNA (mRNA) distribution was studied in human atherosclerotic plaque tissue by in situ hybridization (ISH). The strongest ET-1-like immunoreactivity (ET-1-IR) was present in all cell-rich areas of 27 plaques. In fibrotic areas of 27 tissue samples, ET-1-IR was found in 44 per cent (12/27). ET expression was most prevalent in foamy macrophages (MPs, HAM 56-positive) and myofibroblasts (MFBs, alpha-actin-positive) in the vicinity of necrotic areas with signs of previous intraplaque haemorrhage. By contrast, ET-1-IR was weak and inconsistently found in MPs (11/27; 40 per cent) and MFBs (12/27; 44 per cent) in fibrous areas. Luminal endothelial cells (Ulex europeus agglutinin reaction-positive, UEA) exhibited strong ET-1-IR, whereas endothelial cells of intraplaque microvessels demonstrated inconsistent staining for ET-1. ISH revealed that ET mRNA is produced locally in intimal MPs showing strong ET-1-IR. These findings demonstrate that ET-1 is produced by human MPs, the principal inflammatory cell type in atherosclerosis, suggesting a role for ET-1 in the chronic inflammation associated with complicated atherosclerosis.
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PMID:Endothelin-1-like immunoreactivity in human atherosclerotic coronary tissue: a detailed analysis of the cellular distribution of endothelin-1. 877 87

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

The absence of angiographic findings despite significant coronary artery disease has been previously described. Possible explanations for the limitation of plaque detection by angiography include compensatory vessel enlargement in face of intracoronary plaque formation, the lack of reference segments in diffuse atherosclerosis as well as technical limitations. Intracoronary ultrasound (ICUS) imaging provides the possibility of direct plaque visualization. We studied angiographically normal left main coronary arteries (LMCA) in 72 patients prior to diagnostic angiography or therapeutic interventions using ICUS (30 MHz). ICUS images were continuously recorded and recalled from memory for morphometric analysis. Lumen area, plaque area and the total vessel area were determined by computer software. ICUS imaging revealed atherosclerotic plaque in 55 of the 72 patients with angiographically normal LMCA (76%). The average plaque area stenosis was 22 +/- 12% (range 3-44%). Total vessel area showed a significant direct correlation with plaque area, indicating compensation of coronary plaque formation. The average percent change in plaque area (difference between maximal and minimal plaque area within the LMCA) was 11 +/- 19%, indicating a diffuse pattern. Measurement of change in lumen area (difference between maximal and minimal lumen area within the LMCA) revealed an average value of 6 +/- 7%. Lumen area of the LMCA was 15.9 +/- 3.2 mm2 in patients with and 17.2 +/- 1.9 mm2 without atherosclerotic plaque (n.s.). Thus, the lack of angiographic changes despite advanced plaque formation in the LMCA could be explained by compensatory vessel enlargement and by diffuse distribution of plaque in the vessel; true lumen narrowings overlooked by angiography seem not to account for the failure of angiography to detect plaque.
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PMID:Angiographically undetected plaque in the left main coronary artery. Findings of intravascular ultrasound imaging. 930 43

Luminal stenosis can be based on large atherosclerotic plaques in compensatory enlarged segments or on relatively little plaques in shrunken segments. In the present study, the contribution of plaque formation and remodeling to luminal narrowing was compared among six types of arteries prone to symptomatic atherosclerosis. Cross-sections (n = 5195) were obtained at regular intervals from 329 arteries. For each artery, the cross-section that contained the least amount of plaque was considered to be the reference. For each cross-section, the percentage of lumen area decrease was expressed as a percentage of the lumen area at the reference site (luminal stenosis). Similarly, the area encompassed by the internal elastic lamina (IEL area) was expressed as a percentage of the IEL area at the reference site (relative IEL area). All cross-sections were categorized in three groups: relative IEL area > 105% (enlargement), 95% to 105% (no remodeling), and < 95% (shrinkage). The prevalence of enlargement (50% to 75%) was significantly higher compared with shrinkage (8% to 25%). Shrinkage was observed most frequently in the femoral arteries (25%) and infrequently in the renal arteries (8%). For all types of arteries, the relative IEL area correlated negatively with luminal stenosis (P < .001). Regression analysis of relative IEL area on luminal stenosis, however, showed significant differences in the first-order regression coefficients among artery types. On average, plaque increase was more compensated for by enlargement in the coronary, common carotid, and renal arteries compared with the arteries obtained from the lower extremities. Anatomic regional differences were observed in the impact of arterial wall remodeling on percent luminal stenosis in de novo atherosclerotic lesions.
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PMID:The impact of atherosclerotic arterial remodeling on percentage of luminal stenosis varies widely within the arterial system. A postmortem study. 940 93

Occlusive arterial disease stimulates compensatory growth of pre-existent and new arterial channels which help to maintain organ perfusion. Previous studies characterizing compensatory or collateral vascular growth have been performed in normocholesterolemic animals. Because hyperlipidemic states alter vascular regulation, it remains to be demonstrated that the capacity of the vasculature to undergo compensatory growth is preserved in the presence of dyslipidemic vascular injury. To assess effects of hypercholesterolemia on vascular growth, arterial supply to the ear of rabbits with (n = 13) or without hypercholesterolemia (n = 14) was surgically restricted. Compensatory growth of residual arteries and distal microvessels was evaluated using quantitative angiographic and microanatomic methods. Lumen-expanding hyperplasic arterial remodeling and distal microvascular proliferation induced by arterial restriction were assessed by independent techniques including in vivo microangiography, laser Doppler flowmetry, quantitative histometry, and thymidine incorporation. Compared with controls, hypercholesterolemic rabbits exhibited depressions in all arterial and capillary growth indexes. Microvascular proliferation in hypercholesterolemic rabbits was less than 20% of control. Results demonstrate for the first time that an atherogenic dyslipidemia may limit compensatory macro- and microvascular growth in response to arterial restriction, a phenomenon that could play an important role in the pathophysiology of atherosclerotic occlusive artery disease.
Atherosclerosis 1998 Aug
PMID:Impaired adaptive vascular growth in hypercholesterolemic rabbit. 971 30

Because the beta3-antagonist abciximab (c7E3 Fab) has significantly improved late outcomes after coronary angioplasty, the beta3 integrins have been implicated in the arterial response to injury. However, the mechanisms underlying this benefit are unknown. The observation that c7E3 binds beta3 integrins on vascular cells (alphavbeta3) with affinity equal to that for the platelet glycoprotein IIb/IIIa integrin has led to the hypothesis that c7E3 may act directly on the artery wall to prevent restenosis after angioplasty. To test this hypothesis, we studied the effects of c7E3 on structural changes within the artery wall after angioplasty or stent angioplasty in 23 male cynomolgus monkeys with established atherosclerosis. Animals were randomly assigned to receive either a bolus of c7E3 (0.4 mg/kg IV, n=11) followed by a 48-hour infusion (0. 2 microg. kg-1. min-1) or an equal volume of vehicle (n=12). Animals received weight-adjusted aspirin and heparin and then underwent unilateral iliac artery experimental angioplasty and subclavian artery stent angioplasty (Palmaz). Iliac artery lumen diameter (LD) was determined by angiography at baseline (LDPre), after angioplasty (LDPost), and 35 days later (LDDay35). Arteries were then fixed by perfusion and removed for analysis. Lumen, intima, media, and external elastic lamina (EEL) areas were measured in iliac artery cross sections. Values from each injured iliac artery were normalized to the contralateral uninjured iliac artery to control for interanimal variability in baseline artery size and atherosclerosis extent. Intimal area was also measured in subclavian stent cross sections. c7E3 blocked platelet aggregation and prolonged the bleeding time from 2.8+/-1.1 to 19.8+/-2.5 minutes, P<0.001. Experimental angioplasty increased LDPost an average of 28%, and the initial gain was similar in both groups (P=NS). Despite an anti-platelet effect, c7E3 did not inhibit iliac lumen narrowing (LDDay35-LDPost: c7E3, -0.69+/-0.17 versus vehicle, -0.99+/-.17 mm, P=0.35); intimal hyperplasia (neointima area: c7E3, 1.12+/-.28 versus vehicle, 1.22+/-.20 mm2, P=0.77); or decrease in artery wall size (EEL area [percent of uninjured control]: c7E3, 101+/-7% versus vehicle, 121+/-7%). Stent intimal hyperplasia was also unaltered by c7E3 treatment (neointimal area: c7E3, 1.09+/-0.16 versus vehicle, 1. 28+/-0.11 mm2, P=0.36). These results suggest that the benefits of c7E3 treatment in coronary angioplasty were not from inhibition of intimal hyperplasia or improved artery wall remodeling. Alternative mechanisms should be explored to explain improved late outcomes after angioplasty in patients treated with c7E3.
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PMID:Effects of beta3-integrin blockade (c7E3) on the response to angioplasty and intra-arterial stenting in atherosclerotic nonhuman primates. 981 11


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