Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization?

Boer, Onno J. de

doi:10.1016/s0008-6363(98)00255-7

Cited by 229 publications

(157 citation statements)

References 14 publications

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“…22,23 Previous reports have studied plaque neovascularization in advanced atherosclerosis in carotid endarterectomy specimens. 24,25 However, these studies did not evaluate neovascularization across the vessel wall. Our study in aortic sections identified neovessel density within the plaque to be lower than that within the tunica media.…”

Section: Moreno Et Al Neovessels and Plaque Rupture 2035mentioning

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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Section: Moreno Et Al Neovessels and Plaque Rupture 2035mentioning

confidence: 99%

Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta

et al. 2004

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“…22 The pivotal work of O'Brien et al 23,24 documented the mechanisms underlying neovessel recruitment of plaque leukocytes in human atherosclerosis. The expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin were 2-to 3-fold higher on neovessels than on arterial luminal endothelium, confirming the predominant role for neovessels as a pathway for leukocyte infiltration in human coronary plaques.…”

Section: Neovascularization and Leukocyte Recruitmentmentioning

confidence: 99%

Neovascularization in Human Atherosclerosis

Moreno¹,

Purushothaman²,

Zias³

et al. 2006

CMM

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“…13,14 Thus, the neovessels in atherosclerotic plaques express leukocyte adhesion molecules and are therefore able to sustain the influx of leukocytes into the plaque. 28 Importantly, the neovessels may also act as a port of entry for circulating MC progenitors to the deep areas of the plaques. In addition, rupture of the fragile walls of the neovessels may allow erythrocytes to leak into the plaque.…”

Section: Lappalainen Et Al Bfgf In Mast Cells In Human Coronary Arteriesmentioning

confidence: 99%

Mast Cells in Neovascularized Human Coronary Plaques Store and Secrete Basic Fibroblast Growth Factor, a Potent Angiogenic Mediator

Lappalainen

Laine

Pentikäinen

et al. 2004

ATVB

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Objective-Intraplaque neovascularization and hemorrhage may facilitate plaque progression. We studied expression of basic fibroblast growth factor (bFGF), a potent angiogenic mediator, by mast cells (MCs) in human coronary plaques with increasing degrees of atherosclerosis. Methods and Results-Normal and atherosclerotic coronary segments were collected from 30 autopsied subjects.Immunohistochemical methods were used to detect MCs, bFGF, and microvessels. Both adventitial and intimal MCs showed intracytoplasmic granular staining for bFGF, and bFGF-positive extracellular granules were observed close to the MCs. Increased numbers of bFGF-positive MCs were detected in neovascularized areas of plaques, and there was a positive correlation between numbers of bFGF-positive MCs and microvessels in both the intima and adventitia. In plaques, the highly neovascularized areas contained increased numbers of bFGF-positive MCs compared with the adjacent nonvascularized areas, where only few MCs were present. Importantly, the proportion of intimal MCs expressing bFGF increased with increasing severity of atherosclerosis. Conclusions-The present work reveals a novel source of bFGF in human coronary arteries, the intimal and adventitialMCs. See coverExpression of bFGF has been found in human atherosclerotic plaques (eg, in femoral, carotid, and coronary arteries), with the cell types responsible for bFGF expression being ECs, SMCs, and macrophages. [2][3][4] Increased expression of bFGF is found in coronary atherectomy specimens from patients with clinically unstable angina, compared with specimens from patients with stable coronary disease. 2 Moreover, bFGF is 1 of the angiogenic growth factors currently studied to induce therapeutic angiogenesis in ischemic human tissues. 5,6 The mast cell (MC) is a type of inflammatory cell implicated in angiogenesis. 7 In human coronary atheromas, MCs appear near intimal neovessels, 8 and in the adventitia, MCs are often located close to the vasa vasorum. 9 These localizations of coronary MCs suggest that in coronary atheromas they may contribute to neoangiogenesis. Increased numbers of bFGF-positive MCs have been found in tissues characterized by neovascularization, fibrosis, and inflammation, such as human fibrotic lung and cutaneous hemangiomas. 10,11 In MCs, bFGF is located predominantly in the heparincontaining granules. 12 The emerging concept of intraplaque neovascularization and hemorrhage as factors contributing to plaque progression 13,14 prompted us to search for bFGF in MCs in human coronary arteries showing various degrees of atherosclerosis. Methods Autopsy MaterialThe autopsy series comprised 30 cases (24 men and 6 women) aged 34 to 78 years. The proximal left coronary artery was removed, cut into successive segments 5 mm long, fixed in neutral buffered formalin, and embedded in paraffin. Sections (2 to 4 m) were stained with hematoxylin-eosin and elastica-van Gieson and evalu- ImmunohistochemistryThe tissue sections were deparaffinized and rehydrated, and endogenous peroxid...

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Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization?

Abstract: Neovascularisation and expression of adhesion molecules by microvessels at sites of vulnerable lipid-rich plaques may sustain the influx of inflammatory cells and hence, could contribute to plaque destabilization.

Cited by 229 publications

References 14 publications

Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta

Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta

Neovascularization in Human Atherosclerosis

Mast Cells in Neovascularized Human Coronary Plaques Store and Secrete Basic Fibroblast Growth Factor, a Potent Angiogenic Mediator

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