Neovascularization in atherectomy specimens from patients with unstable angina: Implications for pathogenesis of unstable angina

Tenaglia, Alan N.; Peters, Kevin G.; Sketch, Michael H.; Annex, Brian H.

doi:10.1016/s0002-8703(98)70336-9

Cited by 154 publications

(79 citation statements)

References 13 publications

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“…9,10 Angiogenesis occurs in association with remodeling and protease activation in the surrounding tissues. 11,12 Therefore, factors that stimulate plaque angiogenesis could also contribute to activities that promote plaque disruption, the event often responsible for myocardial infarction and ischemic stroke.…”

Section: See P 1653mentioning

confidence: 99%

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

et al. 1999

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Background-Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in the progression of atherosclerosis is unknown. In this report, we first demonstrate that intimal vessels occur in advanced lesions of apolipoprotein E-deficient (apoE Ϫ/Ϫ) mice. To test the hypothesis that intimal vessels promote atherosclerosis, we investigated the effect of angiogenesis inhibitors on plaque growth in apoE Ϫ/Ϫ mice. Methods and Results-ApoE Ϫ/Ϫ mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant mouse endostatin, 20 mg ⅐ kg Ϫ1 ⅐ d

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Section: See P 1653mentioning

confidence: 99%

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

et al. 1999

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“…4,5 In addition, microvessels are increased in coronary lesions from patients with acute myocardial infarction, suggesting a potential role for microvessels in plaque rupture. 6,7 Histological features associated with plaque rupture include a large lipid core, thin fibrous cap, and increased inflammation. 8 Furthermore, rupture of the internal elastic lamina (IEL) is also seen in complex plaques.…”

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confidence: 99%

Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta

et al. 2004

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Background-Growth of atherosclerotic plaques is accompanied by neovascularization from vasa vasorum microvessels extending through the tunica media into the base of the plaque and by lumen-derived microvessels through the fibrous cap. Microvessels are associated with plaque hemorrhage and may play a role in plaque rupture. Accordingly, we tested this hypothesis by investigating whether microvessels in the tunica media, the base of the plaque, and the fibrous cap are increased in ruptured atherosclerotic plaques in human aorta. Methods and Results-Microvessels, defined as CD34-positive tubuloluminal capillaries recognized in cross-sectional and longitudinal profiles, were quantified in 269 advanced human plaques by bicolor immunohistochemistry. Macrophages/T lymphocytes and smooth muscle cells were defined as CD68/CD3-positive and ␣-actin-positive cells. Total microvessel density was increased in ruptured plaques when compared with nonruptured plaques (Pϭ0.0001). Furthermore, microvessel density was increased in lesions with severe macrophage infiltration at the fibrous cap (Pϭ0.0001) and at the shoulders of the plaque (Pϭ0.0001). In addition, microvessel density was also increased in lesions with intraplaque hemorrhage (Pϭ0.04) and in thin-cap fibroatheromas (Pϭ0.038). Logistic regression analysis identified plaque base microvessel density (Pϭ0.003) as an independent correlate to plaque rupture. Conclusions-Thus, neovascularization as manifested by the localized appearance of microvessels is increased in ruptured plaques in the human aorta. Furthermore, microvessel density is increased in lesions with inflammation, with intraplaque hemorrhage, and in thin-cap fibroatheromas. Microvessels at the base of the plaque are independently correlated with plaque rupture, suggesting a contributory role for neovascularization in the process of plaque rupture. (Circulation.

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“…1 Extensive neovascular proliferation within atherosclerotic plaques is prominent within "culprit" lesions clinically associated with unstable angina, myocardial infarction, and stroke. [2][3][4] Plaque angiogenesis has been suggested to promote plaque growth, intraplaque hemorrhage, 5 and lesion instability.Magnetic resonance (MR) molecular imaging of focal angiogenesis in vivo with integrin-targeted paramagnetic contrast agents was reported with perfluorocarbon nanoparticles 6 -8 and liposomes. 9 Subsequently, we have developed MRI and postprocessing techniques to permit molecular imaging of the diffuse proliferating neovasculature associated with atherosclerotic plaque development.…”

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confidence: 99%

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confidence: 99%

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

Winter

Neubauer

Caruthers

et al. 2006

ATVB

364

302

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Objective-Angiogenic expansion of the vasa vasorum is a well-known feature of progressive atherosclerosis, suggesting that antiangiogenic therapies may stabilize or regress plaques. ␣ ␤ 3 Integrin-targeted paramagnetic nanoparticles were prepared for noninvasive assessment of angiogenesis in early atherosclerosis, for site-specific delivery of antiangiogenic drug, and for quantitative follow-up of response. Methods and Results-Expression of ␣ ␤ 3 integrin by vasa vasorum was imaged at 1.5 T in cholesterol-fed rabbit aortas using integrin-targeted paramagnetic nanoparticles that incorporated fumagillin at 0 g/kg or 30 g/kg. Both formulations produced similar MRI signal enhancement (16.7%Ϯ1.1%) when integrated across all aortic slices from the renal arteries to the diaphragm. Seven days after this single treatment, integrin-targeted paramagnetic nanoparticles were readministered and showed decreased MRI enhancement among fumagillin-treated rabbits (2.9%Ϯ1.6%) but not in untreated rabbits (18.1%Ϯ2.1%). In a third group of rabbits, nontargeted fumagillin nanoparticles did not alter vascular ␣ ␤ 3 -integrin expression (12.4%Ϯ0.9%; PϾ0.05) versus the no-drug control. In a second study focused on microscopic changes, fewer microvessels in the fumagillin-treated rabbit aorta were counted compared with control rabbits. Conclusions-This study illustrates the potential of combined molecular imaging and drug delivery with targeted nanoparticles to noninvasively define atherosclerotic burden, to deliver effective targeted drug at a fraction of previous levels, and to quantify local response to treatment. Key Words: magnetic resonance imaging Ⅲ atherosclerosis Ⅲ molecular imaging Ⅲ angiogenesis Ⅲ nanoparticles Ⅲ fumagillin A key feature of the atherosclerotic process is the angiogenic expansion of the vasa vasorum in the adventitia, which extends into the thickening intimal layer of the atheroma in concert with other neovessels originating from the primary arterial lumen. 1 Extensive neovascular proliferation within atherosclerotic plaques is prominent within "culprit" lesions clinically associated with unstable angina, myocardial infarction, and stroke. [2][3][4] Plaque angiogenesis has been suggested to promote plaque growth, intraplaque hemorrhage, 5 and lesion instability.Magnetic resonance (MR) molecular imaging of focal angiogenesis in vivo with integrin-targeted paramagnetic contrast agents was reported with perfluorocarbon nanoparticles 6 -8 and liposomes. 9 Subsequently, we have developed MRI and postprocessing techniques to permit molecular imaging of the diffuse proliferating neovasculature associated with atherosclerotic plaque development. 10,11 The widespread expression of ␣ ␤ 3 integrins observed by MR agreed with the diffuse nature of angiogenesis microscopically observed in the early atherosclerotic aortas of cholesterol-fed rabbits.The importance of angiogenesis in the progression of atherosclerotic plaque combined with the antiangiogenic impact of 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase ...

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Neovascularization in atherectomy specimens from patients with unstable angina: Implications for pathogenesis of unstable angina

Cited by 154 publications

References 13 publications

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta

Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

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Neovascularization in atherectomy specimens from patients with unstable angina: Implications for pathogenesis of unstable angina

Cited by 154 publications

References 13 publications

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta

Endothelial α ν β 3 Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

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Endothelial α _ν β ₃ Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis