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

Imaging atherosclerosis may help to identify subjects harboring rupture-prone atherosclerotic plaques who may benefit from preventive interventions. Potential of plaques to rupture depends on their structural changes and metabolic activation, which are difficult to assess using anatomic imaging modalities. Recent studies suggested that functional imaging with positron emission tomography (PET) utilizing fluorine-18-labeled 2-deoxy-d-glucose (FDG) has the potential to assess plaque metabolism and add to prediction of vascular risk. Aortic, iliac, and carotid plaques can be detected with FDG-PET, even though not all plaques exhibit high FDG uptake. Detection of coronary artery plaques is more cumbersome due to technical limitations of PET and fast movement of these vessels during cardiac and respiratory cycles. Studies on substrate accumulating FDG in plaques are contradictory and mostly do not extend beyond correlation analyses. Vascular FDG uptake has an excellent short-term stability, but larger fluctuations of uptake long-term, which may complicate interpretation of such changes in therapeutic trials. FDG uptake in major arteries correlates with some cardiovascular risk factors and atherosclerosis markers, but clinical utility of such correlations is unclear. What is more important is that recently reported studies in cancer patients showed correlation between higher baseline FDG uptake and subsequent cardiovascular mortality. Anti-atherogenic therapy and therapeutic lifestyle changes seem to decrease vascular FDG uptake but it is not clear whether the latter predicts subsequent lower morbidity and mortality. These initial findings suggest that vascular FDG-PET may in the future find some utility in management of patients with atherosclerosis, but a number of important issues need to be addressed first. We need to: (1) determine optimal standard ways of performing imaging and quantifying vascular FDG uptake; (2) understand molecular mechanisms governing FDG accumulation in plaques; (3) perform studies prospectively linking vascular FDG uptake to cardiovascular events in non-cancer patients. As of today, vascular FDG-PET is not ready for its prime time in clinical practice.
Atherosclerosis 2010 Aug
PMID:FDG-PET imaging of atherosclerosis: Do we know what we see? 2020 37

Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.
 ...
PMID:Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis. 2102 95

Epidemiological evidence demonstrates positive correlation between environmental and occupational arsenic or fluoride exposure and risk to various cardio-respiratory disorders. Arsenic-exposure has been associated with atherosclerosis, hypertension, cerebrovascular diseases, ischemic heart disease, and peripheral vascular disorders, whereas Fluoride-exposure manifests cardiac irregularities and low blood pressure (BP). Present study aims to study the combined effects of these toxicants on various cardio-respiratory variables in male rats. Single intravenous (i.v.) dose of arsenic (1, 5, 10 mg/kg) or fluoride (5, 10, 20, 36.5 mg/kg) either alone or in combination were administered. Individual exposure to arsenic or fluoride led to a significant depletion of mean arterial pressure, heart rate (HR), respiration rate and neuromuscular (NM) transmission in a dose-dependent manner. These changes were accompanied by increased levels of blood reactive oxygen species (ROS) and decreased glutathione (GSH) concentrations. An increase in the blood acetyl cholinesterase (AChE) activity was observed in both arsenic or fluoride exposed rats. These changes were significantly more pronounced in arsenic-exposed animals than in fluoride. During combined exposure to arsenic (5 mg/kg) + fluoride (20 mg/kg) or arsenic (10 mg/kg) + fluoride (36.5 mg/kg) the toxic effects were more pronounced compared to individual toxicities of arsenic or fluoride alone. However, combined exposure to arsenic (5 mg/kg) + fluoride (36.5 mg/kg) resulted in antagonistic effects on variables suggestive of altered cardio-respiratory function and oxidative stress. The results from the present study suggest that arsenic or fluoride individually demonstrate cardio-respiratory failure at all doses whereas during combination exposure these toxins show variable toxicities; both synergistic and antagonistic effects depending upon the dose. Moreover, it may be concluded that arsenic and/or fluoride cardio-respiratory toxicity may be mediated via oxidative stress. However, these results are new in the discipline thus requires further exploration.
 ...
PMID:Interactive effect of arsenic and fluoride on cardio-respiratory disorders in male rats: possible role of reactive oxygen species. 2124 4

The aim of this study was to examine the degree and prevalence of regional (aorta) and global (cardiac) fluorine-18-sodium fluoride ((18)F-NaF) uptake by positron emission tomography (PET)-computed tomography (CT) as evidence for calcification in the atherosclerotic plaques in the aorta and the heart as a function of age. Image data from 51 patients, who had undergone whole-body (18)F-NaF-PET/CT, were evaluated retrospectively. Cardiac and arterial (aorta) radiotracer uptakes were analyzed quantitatively by measuring standard uptake values (SUV). This approach involved examining the entire heart and various aortic segments as identified by CT. By combining CT and PET data, regional and global concentrations of this molecule were calculated and correlated with age over the decades. (18)F-NaF uptake in the heart and aorta increased significantly with advancing age (P<0.01). The Pearson correlation coefficient for the mean (18)F-NaF uptake of cardiac region and 5 age groups was 0.92 (P=0.003) and for aorta and 5 age groups was 0.97 (P=0.004). In conclusion, these preliminary data indicate the feasibility of (18)F-NaF-PET/CT for measurement of regional and global calcification of the heart and major arteries. The (18)F-NaF-PET/CT may provide highly relevant information about the state of calcified plaque before structural calcification is detectable by standard CT techniques. This, therefore, may allow for earlier intervention for risk reduction in cardiovascular diseases. Further studies are needed to validate the role of this promising technique in the management of patients with suspected atherosclerosis.
 ...
PMID:Detection and global quantification of cardiovascular molecular calcification by fluoro18-fluoride positron emission tomography/computed tomography--a novel concept. 2176 Oct 11

For decades, the identification of significant luminal narrowing has been the hallmark to characterize the presence and extent of coronary artery disease. However, it is now known that characterizations of systemic atherosclerosis burden and inflammation, as well as the local quality of plaque composition and morphology, allow better characterization of coronary artery disease and thus may allow improved prediction of adverse cardiovascular events. Plaque characterized histologically as a thin-cap fibroatheroma (ie, an atheroma with a thin fibrous cap, an underlying lipid-rich necrotic core, and inflammatory activity) has been recognized as representing vulnerable or high-risk plaque. Positron emission tomography (PET) and cardiac computed tomography (CT) are noninvasive modalities that provide metabolic (PET) and morphologic (CT) information about atherosclerotic plaque. PET allows the quantification of the uptake of fluorine 18 fluorodeoxyglucose (FDG) within the arterial wall, which provides a measure of macrophage activity within atheromatous plaque. Coronary CT allows the depiction of plaque morphology and composition. Thus, integrated imaging with PET and CT (PET/CT) permits coregistration of FDG activity with the presence and morphology of plaque and may lead to improved characterization of vulnerable plaque or vulnerable patients, or both. This review details the methods and principles of cardiac FDG PET and coronary CT and provides an overview of the research, with an emphasis on the identification and characterization of vulnerable plaque.
 ...
PMID:Complementary value of cardiac FDG PET and CT for the characterization of atherosclerotic disease. 2191 43

Apolipoprotein A-I (ApoA-I), a primary protein component of high-density lipoprotein (HDL), plays an important role in cholesterol metabolism mediating the formation of HDL and the efflux of cellular cholesterol from macrophage foam cells in arterial walls. Lipidation of ApoA-I is mediated by adenosine triphosphate (ATP) binding cassette A1 (ABCA1). Insufficient ABCA1 activity may lead to increased risk of atherosclerosis due to reduced HDL formation and cholesterol efflux. The standard radioactive assay for measuring cholesterol transport to ApoA-I has low throughput and poor dynamic range, and it fails to measure phospholipid transfer. We describe the development of two sensitive, nonradioactive high-throughput assays that report on the lipidation of ApoA-I: a homogeneous assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) and a discontinuous assay that uses the label-free Epic platform. The TR-FRET assay employs HiLyte Fluor 647-labeled ApoA-I with N-terminal biotin bound to streptavidin-terbium. When fluorescent ApoA-I was incorporated into HDL, TR-FRET decreased proportionally to the increase in the ratio of lipids to ApoA-I, demonstrating that the assay was sensitive to the amount of lipid bound to ApoA-I. In the Epic assay, biotinylated ApoA-I was captured on a streptavidin-coated biosensor. Measured resonant wavelength shift was proportional to the amount of lipids associated with ApoA-I, indicating that the assay senses ApoA-I lipidation.
 ...
PMID:Lipid-sensing high-throughput ApoA-I assays. 2281 78

The emerging demand for programmable functionalization of existing base nanocarriers necessitates development of an efficient approach for cargo loading that avoids nanoparticle redesign for each individual application. Herein, we demonstrate in vivo a postformulation strategy for lipidic nanocarrier functionalization with the use of a linker peptide, which rapidly and stably integrates cargos into lipidic membranes of nanocarriers after simple mixing through a self-assembling process. We exemplified this strategy by generating a VCAM-1-targeted perfluorocarbon nanoparticle for in vivo targeting in atherosclerosis (ApoE-deficient) and breast cancer (STAT-1-deficient) models. In the atherosclerotic model, a 4.1-fold augmentation in binding to affected aortas was observed for targeted vs. nontargeted nanoparticles (P<0.0298). Likewise, in the breast cancer model, a 4.9-fold increase in the nanoparticle signal from tumor vasculature was observed for targeted vs. nontargeted nanoparticles (P<0.0216). In each case, the nanoparticle was registered with fluorine ((19)F) magnetic resonance spectroscopy of the nanoparticle perfluorocarbon core, yielding a quantitative estimate of the number of tissue-bound nanoparticles. Because other common nanocarriers with lipid coatings (e.g., liposomes, micelles, etc.) can employ this strategy, this peptide linker postformulation approach is applicable to more than half of the available nanosystems currently in clinical trials or clinical uses.
 ...
PMID:Programmable nanoparticle functionalization for in vivo targeting. 2304 96

The field of nuclear cardiac imaging has evolved from being rather subjective, more "art than a science," to a more objective, digital-based quantitative technique, providing insight into the physiological processes of cardiovascular disorders and predicting patient outcome. In a mere 4 decades of its clinical use, the technology used to image myocardial perfusion has made quantum leaps from planar to single-photon emission computed tomography (SPECT) and now to a more contemporary rapid SPECT, positron emission tomography (PET), and hybrid SPECT-computed tomography (CT) and PET-CT techniques. Meanwhile, radiotracers have flourished from potassium-43 and red blood cell-tagged blood pool imaging to thallium-201 and technetium-99m-labeled SPECT perfusion tracers along with rubidium-82, ammonia N-13, and more recently F-18 fluorine-labeled PET perfusion tracers. Concurrent with this expansion is the introduction of new quantitative methods and software for image processing, evaluation, and data interpretation. Technical advances, particularly in obtaining quantitative data, have led to a better understanding of the physiological mechanisms underlying cardiovascular diseases beyond discrete epicardial coronary artery disease to coronary vasomotor function in the early stages of the development of coronary atherosclerosis, hypertrophic cardiomyopathy, and dilated nonischemic cardiomyopathy. Progress in the areas of molecular and hybrid imaging are equally important areas of growth in nuclear cardiology. However, this paper focuses on the past and future of nuclear myocardial perfusion imaging and particularly perfusion tracers.
 ...
PMID:Journey in evolution of nuclear cardiology: will there be another quantum leap with the F-18-labeled myocardial perfusion tracers? 2323 79

Recent literature demonstrates the potential of fluorine-18 fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) to detect, localize, and quantify the degree of inflammatory changes in the arterial wall due to early atherosclerosis. Our aim was to assess the correlation between the age and 18F-FDG uptake of aortic segments and determine its correlation with respect to in both age and genders. Fluorine-18-FDG uptake in aortic segments in 143 subjects (58 men, 85 women; ages 5-82 years) was evaluated in this study. Subjects were initially grouped according to the gender, and then by age (below or above 50) with at least 26 subjects per group. Mean standardized uptake value (SUV) of ascending aorta, arch, descending thoracic aorta, and abdominal aortic segments were calculated in each subject. Correlative analyses between age and mean SUV of aortic segments in all subjects were undertaken. Mean SUV between genders for all groups were also compared. There was a positive correlation between age and mean SUV of all aortic segments. The correlation values in all aortic segments were higher in subjects below 50 years old compared to those above 50 years in the entire group of patients as well as when they were subdivided and analyzed according to both genders (P<0.001). Descending thoracic and ascending aortic segments in men below 50 years of age had the highest correlation of 18F-FDG uptake and age (0.85 and 0.80, respectively) whereas abdominal aortic segments in men the above 50 years age group had the lowest correlation value (0.20). Comparison between mean SUV in four visible arterial segments between the two genders did not reveal any statistically significant difference. In conclusion, 18F-FDG uptake in aortic segments increases with age irrespective of genders. The increase with age is more significant in younger subjects compared to older subjects for both men and women. This finding may indicate a deceleration in the inflammatory component of atherosclerosis with aging in older subjects.
 ...
PMID:Atherosclerotic inflammatory activity in the aorta and its correlation with aging and gender as assessed by 18F-FDG-PET. 2413 78

Atherosclerosis can be identified by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and is associated with cardiovascular events and all-cause mortality. Inflammation and classification appear jointly in the formation of atherogenesis. Arterial calcification has been also determined by CT, by (18)F-FDG PET and also in the last few years by (18)F-sodium fluoride (NaF) PET. Beheshti et al, have introduced a new concept for the detection of early molecular and cellular calcification in the atherosclerotic plaques of the heart and aorta, based upon the concept of global disease burden, which had been employed earlier using (18)F-FDG PET. Fluorine-18-NaF uptake in the heart and aorta increased significantly with advancing age. In a screening study involving 1,825 individuals, CT coronary artery calcification (CAC) was found to be common in healthy middle-aged individuals with a low Heart Score and, on the contrary, high-risk subjects very frequently did not have CAC. It is obvious that atherosclerosis appears early in life and also that the actual limits of atherosclerosis related to serious cardiovascular events should be determined by more research, since atherosclerosis is not the only cause of these episodes. It is possible that (18)F-NaF PET/CT may provide information about ongoing active molecular calcification in the plaque before calcification as a cause of cardiovascular episodes is detectable. Global molecular cardiovascular calcification, before becomes macroscopically visible, before it can be identified by CT, may be assessed by nuclear medicine procedures. (18)-NaF PET/CT is the first non-invasive imaging method to identify and localize high risk coronary plaque, a new frontier in nuclear cardiology. The above nuclear medicine diagnostic technique is a major and historical new application, for the diagnosis and the study of cardiovascular diseases, by which a certain tissue per se can be identified.
...
PMID:Diagnosing atherosclerosis makes Nuclear Medicine a tissue imaging modality. 2470 91


<< Previous 1 2 3 4 Next >>