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)

The ability to specifically image macrophages may enable improved detection and characterization of atherosclerosis. In this study we evaluated the in vitro uptake of gadolinium (Gd)-containing immunomicelles (micelles linked to macrophage-specific antibody), micelles, and standard contrast agents by murine macrophages, and sought to determine whether immunomicelles and micelles improve ex vivo imaging of apolipoprotein E knockout (ApoE KO) murine atherosclerosis. Murine RAW 264.7 macrophages were incubated with Gd-DTPA, micelles, and immunomicelles. Cell pellets were prepared and imaged using a 1.5 T MR system with an inversion recovery spin-echo sequence to determine the in vitro T1 values. Ex vivo analysis of mouse aortas was performed using a 9.4T MR system with a high-spatial-resolution sequence (78x39x78 microm3). The T1 value was significantly decreased in cells treated with micelles compared to Gd-DTPA (P<0.0001), and in cells incubated at 4 degrees C with immunomicelles compared to micelles (P<0.05). Ex vivo MRI signal intensity (SI) was significantly increased by 81% and 20% in aortas incubated with immunomicelles and micelles, respectively. Confocal microscopy demonstrated in vitro and ex vivo uptake of fluorescent immunomicelles by macrophages. Immunomicelles and micelles improve in vitro and ex vivo MR detection of macrophages, and may prove useful in the detection of macrophage-rich plaques.
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PMID:MRI to detect atherosclerosis with gadolinium-containing immunomicelles targeting the macrophage scavenger receptor. 1690 77

The purpose of this in vivo MRI study was to quantify changes in atherosclerotic plaque morphology prospectively and to identify factors that may alter the rate of progression in plaque burden. Sixty-eight asymptomatic subjects with >or=50% stenosis, underwent serial carotid MRI examinations over an 18-month period. Clinical risk factors for atherosclerosis, and medications were documented prospectively. The wall and total vessel areas, matched across time-points, were measured from cross-sectional images. The normalized wall index (NWI=wall area/total vessel area), as a marker of disease severity, was documented at baseline and at 18 months. Multiple regression analysis was used to correlate risk factors and morphological features of the plaque with the rate of progression/regression. On average, the wall area increased by 2.2% per year (P=0.001). Multiple regression analysis demonstrated that statin therapy (P=0.01) and a normalized wall index >0.64 (P=0.001) were associated with a significantly reduced rate of progression in mean wall area. All other documented risk factors were not significantly associated with changes in wall area. Findings from this study suggest that increased normalized wall index and the use of statin therapy are associated with reduced rates of plaque progression amongst individuals with advanced, asymptomatic carotid atherosclerosis.
Atherosclerosis 2007 Oct
PMID:Predictors of carotid atherosclerotic plaque progression as measured by noninvasive magnetic resonance imaging. 1697 32

Various methods have been used to quantify atherosclerosis, beginning in the mid-1980s with ultrasound measurement of carotid intima-media thickness (IMT), and going on to coronary calcification assessed by electron-beam CT, measurement of carotid plaque by ultrasound, and measurement of carotid wall thickness by MRI. In recent years, it has become clear that carotid IMT, coronary calcification and carotid plaque reflect biologically and genetically different aspects of the atherosclerotic process, and will respond differentially to therapy. IMT represents mainly hypertensive medial hypertrophy; this measure is more predictive of stroke than of myocardial infarction, and is only weakly associated with traditional coronary risk factors. Carotid plaque area, on the other hand, is more strongly associated with traditional risk factors, and is more predictive of myocardial infarction than of stroke. A quantitative trait, called 'unexplained atherosclerosis', expresses the extent to which an individual has excess carotid plaque not explained by traditional risk factors, or the extent to which an individual is protected from traditional risk factors. Unexplained progression of plaque is an even more powerful tool for genetic research, because age, which accounts for the greatest proportion of baseline plaque, has much less influence on the rate of progression. Compared with IMT, measurement of carotid plaque volume by three-dimensional ultrasound reduces by two orders of magnitude the sample size and duration of treatment needed to evaluate new therapies. Measurement of carotid plaque is, therefore, an important tool for patient management, genetic research and evaluation of new therapies for stroke prevention.
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PMID:Technology Insight: ultrasound measurement of carotid plaque--patient management, genetic research, and therapy evaluation. 1705 48

Diabetes mellitus (DM) is an independent and distinct risk factor of ischemic heart disease. Therefore, early identification and management of coronary atherosclerosis for patients with DM is being desired. For the purpose of visualizing coronary atherosclerosis, various imaging modalities have been proposed especially to identify an unstable plaque that has a thin fibrous cap and a large lipid core. These modalities include intravascular ultrasound, coronary angioscopy, intracoronary thermography, optical coherence tomography, multi-slice CT, MRI, and so on. The development of these modalities are now pushing all cardiologists to get interested in a new field called as "plaque imaging".
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PMID:[Current status and perspectives of coronary imaging for patients with diabetes mellitus]. 1708 96

Individuals who show exaggerated blood pressure reactions to psychological stressors are at increased risk for hypertension, atherosclerosis, and stroke. We tested whether individuals who show exaggerated stressor-induced blood pressure reactivity also show heightened stressor-induced neural activation in brain areas involved in controlling the cardiovascular system. In a functional MRI study, 46 postmenopausal women (mean age: 68.04; SD: 1.35 years) performed a standardized Stroop color-word interference task that served as a stressor to increase blood pressure. Across individuals, a larger task-induced rise in blood pressure covaried with heightened and correlated patterns of activation in brain areas implicated previously in stress-related cardiovascular control: the perigenual and posterior cingulate cortex, bilateral prefrontal cortex, anterior insula, and cerebellum. Entered as a set in hierarchical regression analyses, activation values in these brain areas uniquely predicted the magnitude of task-induced changes in systolic (DeltaR(2)=0.54; P<0.001) and diastolic (DeltaR(2)=0.27; P<0.05) blood pressure after statistical control for task accuracy and subjective reports of task stress. Heightened stressor-induced activation of cingulate, prefrontal, insular, and cerebellar brain areas may represent a functional neural phenotype that characterizes individuals who are prone to show exaggerated cardiovascular reactivity.
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PMID:Heightened functional neural activation to psychological stress covaries with exaggerated blood pressure reactivity. 1710 44

Fibrates reduce triglycerides (TG) and increase HDL-cholesterol levels, but there was no report showing plaque regression by fibrates. Using MRI, we investigated the effects of bezafibrate on aortic plaques in 22 dyslipidemic patients. All patients were asked to receive 400mg bezafibrate, but 8 who declined to have bezafibrate became the control group. Changes in vessel wall area (VWA) and lumen area (LA) from baseline to 1-year were evaluated. Bezafibrate reduced TG (-55%) and increased HDL-cholesterol levels (+29%). Bezafibrate reduced HDL size and increased LDL size. In thoracic plaques, bezafibrate reduced VWA (-6%, P<0.001) with no LA change, but VWA slightly progressed without bezafibrate (+5%). In abdominal plaques, bezafibrate reduced VWA (-8%, P<0.001) with LA increase (+3%, P<0.02), but VWA progressed without bezafibrate (+6%). VWA changes in thoracic and abdominal plaques correlated with TG reduction and HDL-cholesterol increase. Notably, VWA change in only abdominal plaques correlated with HDL size reduction and LDL size increase. Thus, bezafibrate induced plaque regression in thoracic and abdominal aortas with marked TG reduction and HDL-cholesterol increase, but the processes of plaque regression and vascular remodeling may differ between thoracic and abdominal aortas. However, because our study was not a controlled, randomized trial, further study is needed.
Atherosclerosis 2008 Jan
PMID:Effect of bezafibrate therapy on atherosclerotic aortic plaques detected by MRI in dyslipidemic patients with hypertriglyceridemia. 1719 67

We investigated the ability of targeted immunomicelles to detect and assess macrophages in atherosclerotic plaque using MRI in vivo. There is a large clinical need for a noninvasive tool to assess atherosclerosis from a molecular and cellular standpoint. Macrophages play a central role in atherosclerosis and are associated with plaques vulnerable to rupture. Therefore, macrophage scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA) were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning microscopy colocalization, macrophage immunostaining and MRI correlation, competitive inhibition, and various other analyses were performed. In vivo MRI revealed that at 24 h postinjection, immunomicelles provided a 79% increase in signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34% using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal laser-scanning microscopy revealed colocalization between fluorescent immunomicelles and macrophages in plaques. There was a strong correlation between macrophage content in atherosclerotic plaques and the matched in vivo MRI results as measured by the percent normalized enhancement ratio. Monoclonal antibodies to MSR were able to significantly hinder immunomicelles from providing contrast enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is related to the macrophage content of the atherosclerotic vessel areas imaged. Immunomicelles may aid in the detection of high macrophage content associated with plaques vulnerable to rupture.
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PMID:Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. 1721 60

Diffusion is the only source of nutrition to the intervertebral discs, and alteration of diffusion is considered to be the final common pathway for disc degeneration. Yet diffusion remains poorly understood due to the paucity of reliable methods to study diffusion noninvasively in humans in vivo. In recent years, postcontrast MRI has emerged as a powerful and reliable tool for analyzing diffusion in lumbar discs. Since it is noninvasive and safe, it can be used to document the process of diffusion temporally over a period of 24 hours. Well-designed studies have shown that diffusion is a very slow process, and that the endplate is the main structure that controls the process of diffusion. Contrast MRI studies have also made it possible to identify endplate breaks in vivo. In the future this technique may be applied to study the influence of smoking, mechanical loading of the discs, abnormal posture, and atherosclerosis of the lumbar arteries on diffusion. These conditions have all been implicated in disc degeneration through a final common pathway of altered diffusion and decreased nutrition. This review article focuses on the current knowledge, methodology, various factors that influence the diffusion properties of the discs, and future applications of this promising technique.
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PMID:Review of postcontrast MRI studies on diffusion of human lumbar discs. 1726 Mar 94

Corin activates pro-A-type naturetic peptide and pro-B-type naturetic peptide into biologically active molecules. We recently identified a minor allele in the corin gene defined by 2 highly linked single nucleotide polymorphisms (T555I and Q568P), which was associated with hypertension in blacks. Because of the direct antihypertrophic effects of the natriuretic peptide system, we hypothesized that the minor corin I555(P568) allele would be associated with an enhanced hypertrophic response to pressure overload. The relationship between systolic blood pressure and indexed left ventricular mass, derived from cardiac MRI, was analyzed in the Dallas Heart Study as a function of corin allele status. The Multi-Ethnic Study of Atherosclerosis was used as a validation cohort. All of the analyses were limited to self-identified blacks without treatment for hypertension. In addition, we genotyped 2114 markers highly informative for African ancestry in the Dallas Heart Study and derived a covariate representing African ancestry for multivariate models. In adjusted analysis, the corin I555(P568) allele was an independent predictor of left-ventricular mass in subjects with elevated systolic blood pressure. Linear spline regression analysis confirmed a significant interaction (P=0.002) between the corin I555(P568) allele and systolic blood pressure as a predictor of left ventricular mass in subjects with systolic blood pressure >120 mm Hg, and this nonlinear interaction was replicated in the Multi-Ethnic Study of Atherosclerosis. In the Dallas Heart Study, the corin I555(P568) allele was also associated with an increased odds for prevalent left ventricular hypertrophy in the presence of untreated hypertension. These data suggest that the corin I555(P568) allele represents a cardiac hypertrophy-sensitizing genetic locus in systemic hypertension.
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PMID:Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload. 1730 58

Calcified carotid plaques are thought to be less likely to be symptomatic than non-calcified plaques. We present a patient with an unusual cerebral embolism that appeared as very high density on CT and was ascertained to derive from a calcified plaque. This 46-year-old male was admitted within 1 hr of sudden aphasia onset. The admission CT scan showed multiple high-intensity lesions that appeared like calcification. They were high intensity on MRI FLAIR images. MRA showed occlusion of the posterior trunk of the middle cerebral artery. As we considered cerebral embolism, the patient received heparin followed by warfarin. Routine MRA and DSA detected no abnormality, however, a carotid echogram showed a hyperechoic plaque at the left carotid bifurcation. As the NASCET method indicated 6.5% stenosis, carotid endarterectomy was not indicated. However, the thrombus at the bifurcation gradually enlarged despite adequate medical treatment (PT-INR 2.2 - 2.7) and we decided to surgically remove the calcified plaque, thought to be the embolus source. We removed the plaque content through a defect in the plaque membrane. Intraoperatively we found that the rapidly enlarging lesion was the plaque content rather than a thrombus. Pathologically, calcification was more dominant than atherosclerosis. His postoperative course was good and he required only aspirin. This case was peculiar in that the calcification mimicked a hyperdensity embolus and that the lesion derived from a calcified plaque which is usually stable. Repeat carotid ultrasonography is easy and useful when routine investigation fails to reveal the embolic source.
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PMID:[Artery-to-artery embolism due to ruptured calcified carotid plaque]. 1735 54


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