The human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane

doi:10.1016/0021-9150(92)90189-N

Atherosclerosis

Volume 94, Issue 1, May 1992, Pages 71-78

https://doi.org/10.1016/0021-9150(92)90189-N Get rights and content

Abstract

The chick chorioallantoic membrane was used to determine whether the carotid atherosclerotic plaque stimulates angiogenesis. Carotid endarterectomy specimens (1 mm³) with fibromuscular plaque (n = 8) and complicated plaque (n = 11) were implanted on the membrane on day nine of incubation and the response evaluated on day 11. Following fixation in situ with 10% formalin the angiogenic response was evaluated by: (1) examining whole membrane mounts, (2) quantitatively from a vascular density index and (3) from a histological study. Unmanipulated chorioallantoic membrane (n = 11) and plaque boiled prior to implantation (n = 6) served as controls. The vascularity of whole mounts of both fibromuscular and complicated plaque was greater than the controls. Vessel density of the membrane was estimated by counting the number of vessels intersecting four concentric circles (144.5 mm total circumference) placed on the formalin fixed membrane. The vascular density index due to the fibromuscular plaque (390.6 ± 8.3) and complicated plaque (391.0 ± 14.9) were similar (P > 0.9) but were significantly greater (P < 0.001) than the unmanipulated membrane (327.9 ± 5.6) or after treatment with the boiled plaque (283.8 ± 15.6). Transforming growth factor β1 confirmed the validity of the experimental model to study angiogenesis. The histology of the chorioallantoic membrane due to either type of plaque was similar. Numerous vessels surrounded the plaque, and intraplaque vessels containing nucleated chick erythrocytes were observed. Although scattered vessels surrounded the boiled plaque, intraplaque vessels were not observed. This study demonstrates that the atherosclerotic plaque has angiogenic properties that may account for the increase in vasa vasorum that is associated with the plaque.

References (21)

J.A. Fryer et al.
Carotid intraplaque hemorrhage, The significance of neovascularity
J. Vasc. Surg.
(1987)
J.W. Dusseau et al.
Hypoxia-induced angiogenesis in chick chorioallantoic membranes: A role for adenosine
Respir. Physiol.
(1988)
R. Eisenstein
Angiogenesis in arteries: Review
Pharmac. Ther.
(1991)
R.A. Ignotz et al.
Transforming growth factor-R stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix
J. Biol. Chem.
(1986)
W. Halfter et al.
The effect of tenascin and embryonic basal lamina on the behavior and morphology of neural crest cells in vitro
Dev. Biol.
(1989)
P. Barath et al.
Detection and localization of tumor necrosis factor in human atheroma
Am. J. Cardiol.
(1990)
P. Le Compte
Reactions of vasa vasorum in vascular disease
E. Geiringer
Intimal vasculation and atherosclerosis
J. Pathol. Bacteriol.
(1951)
J.C. Paterson et al.
Vascularization of early atherosclerotic plaques
Arch. Pathol.
(1957)
A.C. Barger et al.
Hypothesis: Vasa vasorum and neovascularization of human coronary arteries, a possible role in the pathophysiology of arteriosclerosis
N. Engl. J. Med.
(1984)

There are more references available in the full text version of this article.

Cited by (19)

Captopril suppresses Post-transplantation angiogenic activity in rat allograft coronary vessels
2004, Journal of Heart and Lung Transplantation
The development of transplant coronary artery disease is associated with neovascularization in the thickened neointima. We previously reported that captopril inhibits neointimal proliferation in a rat allograft model. We postulated that angiogenic inducers are upregulated post-transplantation and captopril ameliorates transplant coronary artery disease by suppressing the angiogenic activity of coronaries.
Animals received no treatment or captopril (50 mg/kg/day). Allograft hearts were analyzed at post-transplantation Days 0, 14, and 21 and angiogenic inducer, plasma platelet-activating factor, determined. The conditioned media from coronaries and myocardium were tested for vascular endothelial growth factor, thrombospondin-1 and angiogenic activity using an endothelial migration assay and rat corneal neovascularization assay.
The captopril-treated group had reduced plasma platelet-activating factor and coronary media revealed earlier upregulation of thrombospondin-1 secretion, diminished vascular endothelial growth factor and no angiogenic activity. At Day 0, the coronary and myocardial conditioned medium had inhibitory activity due to thrombospondin-1, and circulating levels of platelet-activating factor were negligible. By 21 days post-transplantation, plasma platelet-activating factor was elevated and the conditioned medium from untreated coronaries had significantly higher angiogenic activity due to increased vascular endothelial growth factor whereas the myocardium remained non-angiogenic.
After transplantation, coronary vessels switch to an angiogenic phenotype and vascular endothelial growth factor contributes to the high angiogenic activity, possibly exacerbated by high circulating levels of platelet-activating factor. The ability of captopril to modulate angiogenic mediators and maintain the allograft coronary to its normal anti-angiogenic phenotype may be one mechanism by which it suppresses transplant coronary artery disease.
Collateral circulation in experimental coarctation of the aorta in minipigs: A possible association with hypertrophied vasa vasorum
2003, Journal of Comparative Pathology
Experimental coarctation of the thoracic aorta was produced in 13 adult Yucatan minipigs by placing a gradually expanding “C-shaped” occluder around the aorta. The aortic constriction was standardized by measuring the blood pressure above the coarctation, with a mean arterial pressure of 165–170 mmHg as the target. The pigs were humanely killed after 8 weeks of hypertension. No deaths were associated with constriction of the aorta, and neither rear limb weakness nor neurological dysfunction was noted. The lack of clinical signs in these animals suggested the development of an extensive collateral circulation. Collateral vessels, which were verified angiographically, included intercostal arteries, muscular intercostal arteries, and the internal thoracic artery. In two of the animals in which the thoracic aorta was completely occluded, revascularization also occurred via small arterial channels. Histologically, there was a marked increase in the number of vessels as well as significant hyperplasia and hypertrophy of smooth muscle of adventitial vasa vasorum. These findings support the hypothesis that collateralization of occluded thoracic aortas may be aided by hypertrophy of the vasa vasorum. To our knowledge, these vessels have not previously been shown convincingly by histopathological methods to revascularize occluded large arteries such as the aorta.
The effect of endothelial cell growth factor on peripheral nerve regeneration
1998, Otolaryngology - Head and Neck Surgery
Neural regeneration after grafting can be unpredictable. In an effort to enhance the return of function after cable graffing, we studied the effects of an angiogenic factor, endothelial cell growth factor (ECGF), on regenerating nerves. Cable grafts on the sciatic nerve were established in 18 rats and treated with ECGF or a control saline solution. At 5 weeks, nerve conduction studies were performed, and the animals were killed for histologic measurements of graft vascularity and axon counts. A significant increase in vascularity was noted in the treated group versus the control group; neither the axon counts nor the nerve conduction velocities differed significantly between the two groups, although the treated group appeared to show improved neural conduction compared with the control group.
Angiogenesis in the pathobiology and treatment of vascular and malignant diseases
1997, Annals of Thoracic Surgery
Cardiovascular disease and cancer account for the majority of adult disease in the developed world. This review focuses on current concepts in the study of angiogenesis (new vessel formation) as related to these conditions and highlights the role of vascular endothelial growth factor. Developments in therapeutic angiogenesis have raised the possibility that pharmacologic or gene-directed interventions, based on the ability of vascular endothelial growth factor to promote new vessel formation, may soon gain clinical application for the treatment of occlusive vascular disease. Similarly, the future treatment of malignant disease is likely to involve antiangiogenic agents that, in preliminary animal work, have demonstrated an efficacy that is not limited by adverse affects. Aside from these potential applications, current investigations have enhanced our understanding of mechanisms involved in the development of atherosclerotic and malignant disease.
Induction of vascular endothelial growth factor gene expression by interleukin-1β in rat aortic smooth muscle cells
1995, Journal of Biological Chemistry
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1β (IL-1β), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1β increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1β increased VEGF mRNA levels by 2-fold and 10 ng/ml IL-1β increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run-on experiments before and after addition of IL-1β to see if IL-1β increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1β, and IL-1β increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1β increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1β induces VEGF gene expression in smooth muscle cells. This IL-1β-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.
The plaque-aortic ring assay: a new method to study human atherosclerosis-induced angiogenesis
2019, Angiogenesis

View all citing articles on Scopus

View full text

Research paperThe human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane

Abstract

J. Vasc. Surg.

Respir. Physiol.

Pharmac. Ther.

J. Biol. Chem.

Dev. Biol.

Am. J. Cardiol.

Reactions of vasa vasorum in vascular disease

Intimal vasculation and atherosclerosis

J. Pathol. Bacteriol.

Vascularization of early atherosclerotic plaques

Arch. Pathol.

Hypothesis: Vasa vasorum and neovascularization of human coronary arteries, a possible role in the pathophysiology of arteriosclerosis

N. Engl. J. Med.

Research paper
The human carotid atherosclerotic plaque stimulates angiogenesis on the chick chorioallantoic membrane