The Year in Atherothrombosis

Sanz, Javier; Moreno, Pedro R.; Fuster, Valentín

doi:10.1016/j.jacc.2007.12.018

Cited by 13 publications

(7 citation statements)

References 102 publications

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“…Cardiovascular disease is the leading cause of morbidity and mortality in developed nations (1). Primarily this is caused by atherosclerosis, a systemic disease, characterized by a chronic inflammation of the arterial wall with concomitant vascular lumen lipid deposits (plaques) (2;3).…”

Section: Introductionmentioning

confidence: 99%

Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis

et al. 2010

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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. 18F-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 non-invasive 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.

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Section: Introductionmentioning

confidence: 99%

Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis

et al. 2010

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“…The lipid deposition in the vessel wall occurs significantly before macrophage infiltration (2). Complications of atherosclerosis, such as plaque rupture, are the most common cause of death in the Western world and are becoming a major health concern in developing countries (1). Previous reports have demonstrated a strong correlation between the lipid core size, thin fibrous cap, and plaque instability (36–38).…”

Section: Discussionmentioning

confidence: 99%

“…The consequences of atherosclerosis represent a critical public health concern in Western countries and are likely to become the major public health problem in the developing world in the near future (1). One of the key initial steps in atherogenesis is the subendothelial retention of apolipoprotein B (ApoB)‐containing lipoproteins (2).…”

mentioning

confidence: 99%

Tyrosine polyethylene glycol (PEG)‐micelle magnetic resonance contrast agent for the detection of lipid rich areas in atherosclerotic plaque

Beilvert

Cormode

Chaubet

et al. 2009

Magnetic Resonance in Med

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Vulnerable or high-risk atherosclerotic plaques often exhibit large lipid cores and thin fibrous caps that can lead to deadly vascular events when they rupture. In this study, polyethylene glycol (PEG)-micelles that incorporate a gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) amphiphile were used as an MR contrast agent. In an approach inspired by lipoproteins, the micelles were functionalized with tyrosine residues, an aromatic, lipophilic amino acid, to reach the lipid-rich areas of atherosclerotic plaque in a highly efficient manner. These micelles were applied to apolipoprotein E -/-(ApoE -/-) mice as a model of atherosclerosis. The abdominal aortas of the animals were imaged using T 1 -weighted (T 1 W) high-resolution MRI at 9.4T before and up to 48 h after the administration of the micelles. PEG-micelles modified with 15% tyrosine residues yielded a significant enhancement of the abdominal aortic wall at 6 and 24 h postinjection (pi) as compared to unmodified micelles. Fluorescence microscopy on histological sections of the abdominal aorta showed a correlation between lipid-rich areas and the distribution of the functionalized contrast agent in plaque. Using a simple approach, we demonstrated that lipid-rich areas in atherosclerotic plaque of ApoE -/-mice can be detected by MRI using Gd-DTPA micelles. Magn Reson Med 62:1195-1201, 2009.

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“…Atherosclerotic disease remains the primary cause of mortality in industrialized countries, despite the clinical advances that have been made in the prevention and treatment of this disease over the past 20 years . Studies have shown that more than two‐thirds of acute coronary syndromes occur in patients who are classified as being at intermediate risk according to traditional Framingham Score risk‐stratification methods.…”

Section: Introductionmentioning

confidence: 99%

Contrast enhancement by lipid‐based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

Adel

Graaf

Que

et al. 2012

Contrast Media & Molecular

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The use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium-based contrast agents to enhance atherosclerotic plaques in ApoE(-/-) mice was evaluated with MRI. We obtained a kinetic profile for contrast enhancement, as the literature data on optimal imaging time points is scarce, and assessed the longer-term kinetics. Signal enhancement in the wall of the aortic arch, following intravenous injection of paramagnetic micelles and liposomes, was followed for 1 week. In vivo T(1)-weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy of NIR(664) incorporated in the contrast agents and quantification of tissue and blood Gd-DTPA. Both micelles and liposomes enhanced contrast in T(1)-weighted MR images of plaques in the aortic arch. The average contrast-to-noise ratio increased after liposome or micelle injection to 260 or 280% respectively, at 24 h after injection, compared with a pre-scan. A second wave of maximum contrast enhancement was observed around 60-72 h after injection, which only slowly decreased towards the 1 week end-point. Confocal fluorescence microscopy and whole body fluorescence imaging confirmed MRI-findings of accumulation of micelles and liposomes. Plaque permeation of contrast agents was not strongly dependent on the contrast agent size in this mouse model. Our results show that intraplaque accumulation over time of both contrast agents leads to good plaque visualization for a long period. This inherent intraplaque accumulation might make it difficult to discriminate passive from targeted accumulation. This implies that, in the development of targeted contrast agents on a lipid-based backbone, extensive timing studies are required.

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The Year in Atherothrombosis

Cited by 13 publications

References 102 publications

Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis

Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis

Tyrosine polyethylene glycol (PEG)‐micelle magnetic resonance contrast agent for the detection of lipid rich areas in atherosclerotic plaque

Contrast enhancement by lipid‐based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

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