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)

Atherosclerotic segments of pigeon aorta synthesized collagen at four times the rate found in normal aorta (Athero = 2071 +/- 1339 ng/g/h; Control = 497 +/- 192 ng/g/h; P less than 0.025). Similar results were obtained when synthesis was expressed per mg DNA. Elevation in collagen synthesis was relatively specific, collagen accounting for 4% of total protein synthesis in lesion-free aorta and 11.5% in atherosclerotic aorta. Substantial increases in total collagen were observed in atherosclerotic aortas (Athero = 9.9 +/- 3.1 mg/aorta; Control = 6.0 +/- 1.3 mg/aorta; P less than 0.05). Ultrastructural studies revealed the accumulation of large amounts of dense fibrillar collagen in the sub-endothelial region of the plaque. Plaque cells contained multiple vacuoles, an extensive rought endoplasmic reticulum and many mitochondria, suggesting active protein synthesis. It is concluded that increased collagen biosynthesis and deposition is an important metabolic derangement in lipid-rich atherosclerotic lesions whihc promotes their gradual conversion to fibrous plaques.
Atherosclerosis 1977 Mar
PMID:Enhanced synthesis and accumulation of collagen in cholesterol-aggravated pigeon atherosclerosis. 84 79

An NHLBI-sponsored randomized, double-masked, placebo-controlled, multicenter clinical trial is underway to test the efficacy of the lipid-lowering agent lovastatin and/or the antithrombotic agent warfarin in slowing the progression of early carotid atherosclerosis--as defined by ultrasonographic intimal-medial arterial wall thickening--in a high-risk, asymptomatic population consisting of 919 men and women aged 40-79 years with moderately elevated serum LDL-cholesterol. The Asymptomatic Carotid Artery Plaque Study's (ACAPS) factorial design permits evaluation of each of the two treatments alone as well as assessment of the treatments in combination with each other over a 2.5- to 3.0-year treatment period. Randomized participants receive either 20-40 mg/day lovastatin or lovastatin placebo and either 1 mg/day (minidose) warfarin or warfarin placebo. All participants were encouraged to take low-dose (81 mg/day) aspirin. The primary outcome is the ultrasonographic measurement of the mean of maximum intimal-medial thickness (IMT) across up to 12 preselected segments in the carotid arteries. The secondary outcome of the trial measures the single maximum IMT measurement among the same preselected carotid artery segments. This report describes the rationale for ACAPS, its design, and some baseline characteristics of the study population.
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PMID:Rationale and design for the Asymptomatic Carotid Artery Plaque Study (ACAPS). The ACAPS Group. 133 Apr 34

Measurements of total collagen, of the ratio of collagen types III/(I+III) and of sulphated glycosaminoglycans (GAGs) were compared with mechanical strength for individual ulcerated and non-ulcerated human aortic plaque caps and with intima adjacent to the plaques. The distributions of the collagen type ratio were similar for both ulcerated and non-ulcerated plaque caps but different from that of the adjacent intima. The proportions of different collagen types were not related to fracture stress and are thus unlikely to affect the potential to ulcerate. The distributions of the sulphated GAGs showed lower amounts for the plaque caps compared with the nearby intima, with the centres of ulcerated plaque caps having the lowest values. Total collagen had higher values in the peripheries of plaque caps compared with the nearby intima, but was distinctly lower in the centres of ulcerated plaque caps. Plaque caps appeared to require a higher collagen content than adjacent intima to support a given level of mechanical strength, suggesting that while collagen production had occurred in the plaque caps it was not as efficiently organized to resist fracture as a similar amount of collagen in the adjacent intima. Ulcerated plaque caps are notable for much larger transverse (centre vs. periphery) gradients of connective tissue constituents than for non-ulcerated plaque caps. The development of these transverse gradients may be a critical aspect in determining the propensity of a plaque to ulcerate.
Atherosclerosis 1992 Sep
PMID:Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: span-wise variations. 141 4

We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino-atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148 +/- 11 to 103 +/- 20 beats/min, p < 0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136 +/- 22 beats/min), animals were separated into a low-heart-rate (LHR) group (111 +/- 16 beats/min, n = 12) and a high-heart-rate (HHR) group (150 +/- 16 beats/min, n = 5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross-sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01 +/- 1.19 compared with 0.76 +/- 0.42 mm2 for lesion area [p < 0.02] and 30.7 +/- 4.4% compared with 15.2 +/- 7.3% for stenosis [p < 0.002]).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate. 142 83

To investigate the role of lipoprotein (a) (Lp[a]) as an atherogenic condition related to hypercholesterolemia, we studied the serum concentration of Lp(a) as measured by immunonephelometry in relation to the presence of asymptomatic echographic plaques in the peripheral arteries of 103 untreated hypercholesterolemic, normotensive, middle-aged men. Plaque was found at carotid, aortic, and femoral sites in 36%, 51%, and 53% of subjects, respectively. The Lp(a) level was higher in the group with carotid plaques than in the group without (0.29 +/- 0.20 versus 0.17 +/- 0.14 g/l, p < 0.01), not significantly higher in the group with aortics plaque than in the group without (0.24 +/- 0.19 versus 0.19 +/- 0.16 g/l), and not different between groups with and without femoral plaques (0.21 +/- 0.18 versus 0.22 +/- 0.17 g/l). A logistic regression analysis confirmed that Lp(a) was associated with carotid plaques (p = 0.004), independent of other risk factors. However, in patients with low density lipoprotein cholesterol values above the group median value (4.7 mmol/l), Lp(a) was associated not only with carotid plaques (p < 0.01) but also with aortic plaques (p < 0.05), as well as with the number of diseased sites (p = 0.02). In contrast, in patients with low density lipoprotein cholesterol levels below or equal to 4.7 mmol/l, Lp(a) only remained associated with carotid plaques (p < 0.05). Thus, in symptom-free, hypercholesterolemic men, early atherosclerosis was influenced by serum Lp(a), particularly in the carotid arteries, as well as by the presence of a higher level of low density lipoprotein cholesterol.
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PMID:Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA Group. 142 94

The study is to evaluate the relationship between extracranial carotid atherosclerosis and ischemic cerebrovascular disease using noninvasive B-mode ultrasonography and X-ray computed tomography. The sensitivity of bruits for diagnosing severe carotid stenosis was also evaluated. A total of 229 consecutive Japanese patients were recruited for this study, of which 97 had chronic-stage ischemic cerebrovascular disease and remaining 132 patients had at least one risk factor for atherosclerosis. Carotid atherosclerosis was evaluated by B-mode ultrasonography. Ischemic cerebrovascular disease was assessed by history taking, neurological findings and X-ray CT examination. The severity of carotid atherosclerosis was assessed by using two indices; plaque score and maximum percentage diameter stenosis. We also evaluated whether it was ulcerated plaque or not. Plaque score was computed by summing up all carotid plaque thicknesses (mm) on both sides. According to the CT findings, cerebral infarction was divided into two types; deep subcortical infarction and cortical infarction. The incidence of cerebral infarction increased in relation to plaque score and maximum percentage stenosis. Although the incidence of cerebral infarction in patients without carotid atherosclerosis was only 33% (38/116), it in patients with moderate carotid atherosclerosis (plaque score > 5) was 59% (26/44) (p < 0.05, chi-square test). The incidence of ipsilateral infarction was revealed to be higher in patients with severe (50% or more) carotid stenosis (61%) than in cases of mild stenosis (28%) (p < 0.05). Thirteen patients had ulcerated plaques and they suffered more frequently cerebral infarction than patients without ulcerated lesions. Cortical infarction was more frequent in patients with severe carotid stenosis than in patients without carotid atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An ultrasonic study of the relationship between extracranial carotid atherosclerosis and ischemic cerebrovascular disease in Japanese]. 146 Jul 77

Ultrasonographic measurement of intima-media thickness in the carotid artery has emerged as an important non-invasive means of assessing atherosclerosis, and has served to define primary outcome measures related to progression of arterial lesions in several large clinical trials and epidemiologic studies. It is characteristic that measurements often cannot be obtained from all sites during repeated examinations. This leads to incomplete multivariate serial data, for which the set and number of visualized sites may vary across time. We have contrasted several conditional and unconditional maximum likelihood analytical approaches, and have evaluated these with a simulation experiment based on characteristics of ultrasound measurements collected during the course of the Asymptomatic Carotid Artery Plaque Study. We examined analyses based on unweighted and generalized least squares regression in which we estimated cross-sectional summary statistics using raw means, unconditional maximum likelihood estimates and full maximum likelihood estimates. Since the genesis of missing data is not fully clear, and since the approaches we examined are based, to some degree, on the assumption that data are missing at random, we also examined the relative impact of deviations from such an assumption on each of the approaches considered. We found that maximum likelihood based approaches increased the expected efficiency of the analysis of serial ultrasound data over ignoring missing data by up to 21 per cent.
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PMID:Analysis strategies for serial multivariate ultrasonographic data that are incomplete. 149 92

The capacity of a multi-gate pulsed Doppler (MPD) system and Doppler color flow imaging (DCFI) for the evaluation of flow patterns was studied in 14 patients with 17 nonstenotic carotid plaques (luminal narrowing less than 40%). Plaque morphology was assessed by means of a high-resolution B-mode system with subsequent three-dimensional reconstruction of the lesion surface. MPD velocity profiles obtained proximally, centrally and distally to the plaque (51 analyses) were normal in 31 sites corresponding to 28 undisturbed and 3 turbulent flow patterns assessed by Doppler color flow imaging (90% specificity). Of the 10 irregular MPD flow profiles, DCFI detected turbulence in 7 (70% sensitivity). 10 asymmetric MPD waveforms without irregularities were normal in 7 and turbulent in 3 DCFI studies. These results suggest, that MPD is superior to DCFI for the detection of nonturbulent flow asymmetry nearby small carotid plaques. However, DCFI displays turbulence with a high specificity and reasonable sensitivity and visualizes the morphologic-hemodynamic interaction in carotid atherosclerosis simultaneously.
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PMID:Comparison of flow disturbances in small carotid atheroma using a multi-gate pulsed Doppler system and Doppler color flow imaging. 156 21

The causes of unstable angina are still largely unknown. However, some facts deriving from angiographic, postmortem, and pathophysiologic studies are well established. Angiographic findings: coronary thrombi and complicated stenoses are more frequent in unstable than in stable angina. Conversely, the severity of coronary atherosclerosis and the development of collateral circulation is similar in both coronary syndromes. Postmortem findings: the following features are more frequent in unstable than in stable angina: (1) mural thrombi, which often represent out-growth from the inside of a fissured plaque; (2) inflammatory cells at the site of plaques and in perivascular nerves; and (3) contraction bands in smooth muscle cells of the media surrounding plaques. However, fissured plaques can be found in 10% of individuals dying of noncardiac causes, and fissured plaque may occasionally be missing under the coronary thrombus in unstable angina. Pathophysiologic findings: patients with unstable angina compared with those with stable angina exhibit: (1) higher levels of serotonin in the coronary sinus; (2) higher systemic levels of fibrino-peptide A; (3) higher urinary levels of thromboxane A2 metabolites; and (4) a greater coronary reactivity to constrictor stimuli. A critical analysis of these established facts is required to set the stage for a better comprehension of the causes which can cause a coronary segment to progress in a stuttering way toward acute persistent coronary occlusion and myocardial infarction. Plaque fissure is likely to be an important background thrombogenic stimulus in many cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The elusive cause of instability in unstable angina. 189 62

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.
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PMID:Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: a morphologic, immunohistochemical, and biochemical study. 189 66


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