Background-Intravascular ultrasound elastography assesses the local strain of the atherosclerotic vessel wall. In the present study, the potential to identify different plaque components in vivo was investigated. Methods and Results-Atherosclerotic external iliac and femoral arteries (nϭ24) of 6 Yucatan pigs were investigated.Before termination, elastographic data were acquired with a 20-MHz Visions catheter. Two frames acquired at end-diastole with a pressure differential of Ϸ4 mm Hg were acquired to obtain the elastograms. Before dissection, x-ray was used to identify the arterial segments that had been investigated by ultrasound. Specimens were stained for collagen, fat, and macrophages. Plaques were classified as absent, early fibrous lesion, early fatty lesion, or advanced fibrous plaque. The average strains in the plaque-free arterial wall (0.21%) and the early (0.24%) and advanced fibrous plaques (0.22%) were similar. Higher average strain values were observed in fatty lesions (0.46%) compared with fibrous plaques (Pϭ0.007). After correction for confounding by lipid content, no additional differences in average strain were found between plaques with and without macrophages (Pϭ0.966). Receiver operating characteristic analysis revealed a sensitivity and a specificity of 100% and 80%, respectively, to identify fatty plaques. The presence of a high-strain spot (strain Ͼ1%) has 92% sensitivity and 92% specificity to identify macrophages. Conclusions-To the best of our knowledge, this is the first time that intravascular ultrasound elastography has been validated in vivo. Intravascular ultrasound (IVUS) has proven to be a powerful technique to assess the geometry of the vessel wall and plaque. However, the sensitivity and specificity to detect lipid cores remains low. 3,4 IVUS elastography assesses the local radial strain in the tissue caused by an intraluminal pressure differential. In vitro experiments revealed different strain values in fibrous and fatty plaques in human coronary and femoral arteries. 5 Feasibility experiments in patients showed that reproducible elastograms could be obtained. 6 The aim of this study was to validate IVUS elastography in vivo with an atherosclerotic Yucatan minipig model. Additionally, we studied whether atheroma and macrophages were related with strain values. Methods AnimalsSix atherosclerotic Yucatan pigs, average weight 40 kg, were studied. To induce atherosclerosis, pigs were put on an atherogenic diet. Two weeks thereafter, the external iliac and femoral arteries were denuded with a 4-F endothelial Fogarty catheter. The atherogenic diet was continued for 9 to 10 months after which femoral and internal iliac arteries were stented for the purpose of another study. Subsequently, the atherogenic diet was replaced by a regular diet. No intervention was performed in the denuded external iliac arteries that were visualized for the present study. The following 42 days, 3 pigs were treated with a drug and 3 pigs served as controls for the purpose of another study. ANOVA reveale...
Cardiovascular disease is the leading cause of death in Western society. Extracellular matrix turnover is important in many cardiovascular pathologies, such as arterial remodeling, plaque rupture, restenosis, aneurysm formation and heart failure. Matrix metalloproteinases (MMPs) belong to a group of zinc and calcium dependent proteases and cause breakdown of the extracellular matrix. MMP inhibitors have been developed and tested for their effect on the outcome of oncological disease [1]. Recent preclinical research revealed that these MMP inhibitors could also have great potential in the field of cardiovascular disease. This preclinical research has encouraged investigators to design and start the first clinical studies with cardiovascular endpoints. In the present paper, the various aspects of MMP participation in cardiovascular disease will be summarized. Preclinical animal studies that demonstrated the effect and potential of applicable MMP inhibitors on different cardiovascular disease entities will be discussed. We will specifically focus on the role of MMPs and the potential of their inhibitors in de novo atherosclerotic plaque destabilization, arterial remodeling, restenosis after ballon angioplasty and stenting, aneurysm formation and heart failure. We conclude that MMP inhibitors are likely to be useful in the development of pharmacological approaches to reduce cardiovascular death, considering the positive outcomes after usage of MMP inhibitors in restenosis and arterial remodeling.
Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling in favor of both neutral and expansive remodeling.
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