期刊
CIRCULATION-CARDIOVASCULAR IMAGING
卷 9, 期 12, 页码 -出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCIMAGING.116.004910
关键词
atherosclerosis; capillary permeability; cardiovascular diseases; magnetic resonance imaging; models, animal
资金
- British Heart Foundation [PG/10/044/28343]
- British Heart Foundation Early Career Development Fellowship
- King's BHF Centre of Research Excellence [BHF RE/08/003]
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St 'Thomas' NHS Foundation Trust
- King's College London
- Chilean Agency of Technology and Science [Fondecyt 1130379]
- National Institute for Health Research (NIHR) Biomedical Research Centre
- St Thomas' NHS Foundation Trust in partnership with King's College London
- NIHR Healthcare Technology Co-operative for Cardiovascular Disease at Guy's
- St Thomas' NHS Foundation Trust
Background Compromised structural integrity of the endothelium and higher microvessel density increase vascular permeability. We investigated whether vascular permeability measured in vivo by magnetic resonance imaging using the albumin-binding contrast agent, gadofosveset, is a surrogate marker of rupture-prone atherosclerotic plaque in a rabbit model. Methods and Results New Zealand white rabbits (n=10) were rendered atherosclerotic by cholesterol-diet and endothelial. denudation. Plaque rupture was triggered with Russell's viper venom and histamine. Animals were imaged pre-triggering, at 3 and 12 weeks, to quantify plaque area, vascular permeability, vasodilation, and stiffness and post-triggering to identify thrombus, Plaques identified on the pretrigger scans were classified as stable or rupture--prone based on the absence or presence of thrombus on the corresponding post-trigger magnetic resonance imaging, respectively. All rabbits had developed atherosclerosis, and 60% had ruptured plaques. Rupture-prone plaques had higher vessel wall relaxation rate (R-1; 2.30 +/- 0.5 versus 1.86 +/- 0.3 s(-1), P<0.001), measured 30 minutes after gadofosveset administration, and higher R-1/plaque area ratio (0.70 +/- 0.06 versus 0.47 +/- 0.02, P = 0,01) compared with stable plaque at 12 weeks, Rupture-prone plaques had higher percent change in Ri between the 3 and 12 weeks compared with stable plaque (50.80 +/- 7.2% versus 14.22 2,2%; P<0.001). hinmunohistochemistry revealed increased vessel wall albumin and microvessel density in diseased aortas and especially in ruptured plaque. Electron microscopy showed lack of structural integrity in both Imninal and microvascular endothelium in diseased vessels. Functionally, the intrinsic vasodilation of the vessel wall decreased at 12 weeks compared with 3 weeks (1.8,60 1,0% versus 23.43 +/- 0.8%; P<0.001) and in rupture-prone compared with stable lesions (16.40 +/- 2.0% versus 21.63 +/- 1.2%; P<0.001). Arterial stiffness increased at 12 weeks compared with 3 weeks (5.00 +/- 0.1 versus 2.53 0.2 m/s; P<0.001.) both in animals with stable and rupture-prone lesions. Conclusions Tl mapping using an albumin-binding contrast agent (gadofosveset) could quantify the changes in vascular permeability associated with atherosclerosis progression and rupture-prone plaques.
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