Statin treated patients have reduced intraplaque angiogenesis in carotid endarterectomy specimens

Koutouzis, Michael; Nomikos, Alexandros; Nikolidakis, Savvas; Tzavara, Vassiliki; Andrikopoulos, Vasilios; Νικολάου, Νικόλαος; Barbatis, Calypso; Kyriakides, Zenon S.

doi:10.1016/j.atherosclerosis.2007.01.035

Cited by 62 publications

(33 citation statements)

References 33 publications

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“…38,39 Many studies have reported that intraplaque angiogenesis plays a role in plaque rupture and therefore causes thrombus formation. 40,41 Previous studies have also reported that atherosclerotic arteries convert arachidonic acid preferentially to 15-HETE. 42,43 Because 15-HETE is produced in atherosclerotic arteries and 12/15-Lox-12/15(S)-HETE axis induces angiogenesis, it is possible that these lipid molecules may play a role in the development of intraplaque angiogenesis.…”

Section: (S)-hete Induces Hmg-coa Reductase Expression 5709mentioning

confidence: 99%

12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation

Singh

Kundumani‐Sridharan

Rao

2011

Blood

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Section: (S)-hete Induces Hmg-coa Reductase Expression 5709mentioning

confidence: 99%

12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation

Singh

Kundumani‐Sridharan

Rao

2011

Blood

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“…This finding is consistent with previous experimental studies that showed neovascularization in atherosclerotic plaque was reduced by statin treatment. 19 On the basis of previous reports, 19 statin treatment may reduce neovascularization via multiple mechanisms (eg, antiinflammatory and antioxidant actions and reduction in the production of angiogenic factors including vascular endothelial growth factor as well as reduction in LDL-C levels). Thus, carotid CEUS imaging might identify changes in plaque neovascularization and thus monitor the therapeutic effects on plaque neovascularization of the carotid artery.…”

Section: Study Limitationsmentioning

confidence: 99%

Contrast-Enhanced Ultrasound Imaging of Carotid Plaque Neovascularization Is Useful for Identifying High-Risk Patients With Coronary Artery Disease

Deyama

Nakamura

Takishima

et al. 2013

Circ J

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A previous study indicated that plaque instability is not merely a local vascular occurrence, 11 but rather exists simultaneously at multiple sites in the systemic vascular bed. It is therefore possible that instability of coronary plaque could be assessed by evaluating plaque neovascularization in the carotid arteries. This study therefore examined whether CEUS of the carotid artery provided information on the severity and instability of coronary artery disease (CAD) and also assessed the efficacy of statin treatment in patients with CAD. ncreased neovascularization in atherosclerotic plaque has been shown to be associated with plaque progression and instability, leading to atherosclerotic occlusive cardiovascular events. 1-3 Contrast-enhanced ultrasound (CEUS) is an emerging valuable tool for visualizing plaque neovascularization in the carotid artery, with the properties of contrast agent microbubbles, making them act as pure intravascular tracers. 3-5 CEUS has the advantages of being a simple and minimally invasive in vivo technique. 3-5 The usefulness and reliability of CEUS have been validated by previous studies in animals and humans that showed the degree of plaque neovascularization assessed by CEUS correlated strongly with histological density of neovessels. 6-8 CEUS also showed a greater extent of plaque neovascularization of the carotid artery in symptomatic patients with previous cerebro- Background: Contrast-enhanced ultrasound (CEUS) in the carotid artery has potential as a technique for imaging plaque neovascularization. This study examined whether CEUS could provide information on the severity and instability of coronary artery disease (CAD).

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“…The first of these manuscripts described the role of angiogenesis in patients with ischemic symptoms, 8 while the second report highlighted the therapeutic role of statins for the treatment of unstable, highly vascular carotid artery plaques. 9 In the first of these two recent articles the authors continued a theme they developed in 1999, which described the relationship between increased carotid plaque neovascularization and symptomatic disease. 7 In their most recent communication in 2007, Dunmore and McCarthy et al stated that the symptomatic carotid plaques have similarities with the immature microvessels observed in tumors and healing wounds.…”

mentioning

confidence: 99%

“…8 The second of the two manuscripts, Koutouzis et al noted a reduction of intra-plaque angiogenesis in patients who received statin therapy for a minimum of 3 months prior to a surgical endarterectomy. 9 Therefore, the goal of our study was to demonstrate that contrast-enhanced carotid ultrasound (CECU) is a novel, non-invasive method for detecting intra-plaque neovascularization.…”

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confidence: 99%

Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis?

et al. 2007

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An atherosclerotic plaque requires a nutrient blood supply, which is predominantly derived from arterial vasa vasorum. A variety of factors (environmental and genetic) contribute to the initiation and growth of atherosclerosis within vessel walls. Chemotactic factors, such as tissue ischemic and hypoxic factors, stimulate the release of vascular endothelial growth factor (VEGF) proteins, resulting in vessel wall angiogenesis. These developments often precede the formation of the luminal plaque. In this report, we describe the use of contrast-enhanced carotid ultrasound (CECU) imaging for the detection and quantification of intra-plaque neovascularization. The efficacy of CECU was measured against the neovascular density observed within the tissue specimens obtained at the time of carotid endarterectomy surgery. The objective of this study was to provide a histologic correlation between CECU and carotid artery atherosclerotic plaque neovascularization. Fifteen patients with significant atherosclerotic carotid artery disease received a CECU examination prior to undergoing a carotid endarterectomy (CEA). Two patients received bilateral endarterectomies, resulting in a total of 17 cases. At the time of surgery, carotid plaque samples were surgically removed and stained with specific vascular markers (CD31, CD34, von Willebrand factor, and hemosiderin) designed to identify the presence and degree of neovascularization. The intra-plaque neovascularization recorded on preoperative CECU was correlated with the degree of neovascularization noted in the tissue specimens. The CECU neovascularization was correlated to CD31-stained tissue specimens. This correlation value was 0.68 using Spearman's rank method. When CECU results were correlated with the other histologic markers (CD34, von Willebrand factor, and hemosiderin), a correlation of 0.50 was obtained. In conclusion, contrast-enhanced carotid ultrasound correlated to the presence and degree of intra-plaque neovascularization as determined from histology specimens.

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Statin treated patients have reduced intraplaque angiogenesis in carotid endarterectomy specimens

Cited by 62 publications

References 33 publications

12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation

12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation

Contrast-Enhanced Ultrasound Imaging of Carotid Plaque Neovascularization Is Useful for Identifying High-Risk Patients With Coronary Artery Disease

Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis?

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