scholarly journals VEGFR2 Blockade in Murine Vein Graft Results in Reduced Intraplaque Hemorrhage and Stable Atherosclerotic Lesions

2014 ◽  
Vol 47 (6) ◽  
pp. 695
Author(s):  
M.R. de Vries ◽  
R.C.M. de Jong ◽  
H.A.B. Peters ◽  
J.F. Hamming ◽  
M.J. Goumans ◽  
...  
Keyword(s):  
Vein Graft ◽  
Intraplaque Hemorrhage ◽  
Atherosclerotic Lesions

Vegfr2 blockade in murine vein graft results in reduced intraplaque hemorrhage and stable atherosclerotic lesions

2014 ◽  
Vol 235 (2) ◽  
pp. e161-e162 ◽  
Author(s):  
M.R. de Vries ◽  
R.C.M. de Jong ◽  
H.A.B. Peters ◽  
J.F. Hamming ◽  
M.J. Goumans ◽  
...  
Keyword(s):  
Vein Graft ◽  
Intraplaque Hemorrhage ◽  
Atherosclerotic Lesions

scholarly journals Prolonged Hyperoxygenation Treatment Improves Vein Graft Patency and Decreases Macrophage Content in Atherosclerotic Lesions in ApoE3*Leiden Mice

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 336 ◽  
Author(s):  
Laura Parma ◽  
Hendrika A. B. Peters ◽  
Fabiana Baganha ◽  
Judith C. Sluimer ◽  
Margreet R. de Vries ◽  
...  
Keyword(s):  
Dna Damage ◽  
Vein Graft ◽  
Thrombus Formation ◽  
Graft Patency ◽  
Intraplaque Hemorrhage ◽  
Long Term Effects ◽  
Atherosclerotic Lesions ◽  
Ros Accumulation

Unstable atherosclerotic plaques frequently show plaque angiogenesis which increases the chance of rupture and thrombus formation leading to infarctions. Hypoxia plays a role in angiogenesis and inflammation, two processes involved in the pathogenesis of atherosclerosis. We aim to study the effect of resolution of hypoxia using carbogen gas (95% O2, 5% CO2) on the remodeling of vein graft accelerated atherosclerotic lesions in ApoE3*Leiden mice which harbor plaque angiogenesis. Single treatment resulted in a drastic decrease of intraplaque hypoxia, without affecting plaque composition. Daily treatment for three weeks resulted in 34.5% increase in vein graft patency and increased lumen size. However, after three weeks intraplaque hypoxia was comparable to the controls, as were the number of neovessels and the degree of intraplaque hemorrhage. To our surprise we found that three weeks of treatment triggered ROS accumulation and subsequent Hif1a induction, paralleled with a reduction in the macrophage content, pointing to an increase in lesion stability. Similar to what we observed in vivo, in vitro induction of ROS in bone marrow derived macrophages lead to increased Hif1a expression and extensive DNA damage and apoptosis. Our study demonstrates that carbogen treatment did improve vein graft patency and plaque stability and reduced intraplaque macrophage accumulation via ROS mediated DNA damage and apoptosis but failed to have long term effects on hypoxia and intraplaque angiogenesis.

scholarly journals PS210. Inhibition of VEGFR2 Reduces Angiogenic Microvessel Leakiness in Murine Vein Graft Atherosclerotic Lesions and Increased Plaque Stability

2014 ◽  
Vol 59 (6) ◽  
pp. 83S-84S
Author(s):  
Margreet de Vries ◽  
Rob C. de Jong ◽  
Erna H. Peters ◽  
Jaap F. Hamming ◽  
Marie José Goumans ◽  
...  
Keyword(s):  
Vein Graft ◽  
Plaque Stability ◽  
Atherosclerotic Lesions

IgG1 phosphorylcholine ameliorates plaque stability via reduced intraplaque angiogenesis and intraplaque haemorrhage in a murine atherosclerosis model

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M De Vries ◽  
F Baganha ◽  
R.C.M De Jong ◽  
H.A.B Peters ◽  
K Petterson ◽  
...  
Keyword(s):  
Vein Graft ◽  
Medical Center ◽  
Animal Experiments ◽  
Atherosclerotic Lesion ◽  
Inflammatory Cells ◽  
Intraplaque Hemorrhage ◽  
Funding Source ◽  
Plaque Stability

Abstract Background Phosphorylcholine, (PC) the polar headgroup of the dominating membrane phospholipid phosphatidylcholine, is one of the main oxLDL epitopes and an important pro-inflammatory damage associated molecular pattern. Experimental and epidemiologic data show that natural anti-PC IgM protect against cardiovascular disease. Within atherosclerotic lesions, inflammatory and angiogenesis processes are interdependent and contribute to plaque destabilization. Atherosclerotic lesion resident CD163+ macrophages promote leukocyte infiltration but also induce angiogenesis and vessel permeability by secreting VEGFA. PC antibodies are recognized for their anti-inflammatory properties. However, the effect of PC antibodies on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH), the main entrance route for inflammatory cells in advanced lesions, is unknown. Purpose To investigate the therapeutic effect of a new IgG1 PC antibody (PCmAB) on lesion development, IPA and IPH in murine vein graft atherosclerosis. Methods All animal experiments were performed in compliance with Dutch government guidelines and the Directive 2010/63/EU of the European Parliament. Hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery. Mice received weekly ip injections of (5mg/kg) PCmAb (n=11) or vehicle (n=12) until sacrifice at day 28. Immunohistochemistry was used to evaluate vein graft morphometry and lesion composition including IPA and IPH. PCmAB isolated effects on pro-angiogenic and pro-inflammatory behaviour was investigated in vitro in HUVECs and Hemoglobin (Hb):Haptoglobin (Hp)-cultured THP-1 macrophages. Results PCmAB treatment decreased vein graft media area (13%) and intima lesion (25%), but more importantly increased lumen area with 53% when compared to vehicle treatment. PCmAb improved lesion stability by increasing collagen content (18%) and by decreasing macrophages presence (31%). VCAM-1 and ICAM-1 expression in the vessel wall were also reduced (resp.29% and 36%) by PCmAb. PCmAb improved IPA by a significant reduction in neovessel density of 34%. This was supported in vitro by significant reduced EC proliferation and migration upon PCmAB with and without oxLDL stimulation. Moreover, PCmAb enhanced maturation of intraplaque angiogenic vessels by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a reduction of IPH of 62% in the PCmAB group. PCmAb resulted in decreased macrophages CD163+ content in vein grafts by 23% whereas CD163 expression was reduced by PCmAb in Hb:Hp stimulated macrophages. Conclusion PCmAB is an effective inhibitor of atherosclerotic lesion formation in ApoE3*Leiden mice. PCmAb reduces IPA and IPH by decreased neovessel density and (CD163+) macrophages influx via reduced expression of VCAM-1 and ICAM-1, and increased neovessel maturation in vein graft atherosclerosis. PCmAB holds a promise as a new therapeutic approach for plaque stability. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Leiden University Medical Center

scholarly journals Both Donor and Recipient Origins of Smooth Muscle Cells in Vein Graft Atherosclerotic Lesions

2002 ◽  
Vol 91 (7) ◽  
Author(s):  
Yanhua Hu ◽  
Manuel Mayr ◽  
Bernhard Metzler ◽  
Martin Erdel ◽  
Fergus Davison ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vein Graft ◽  
Muscle Cells ◽  
Atherosclerotic Lesions

scholarly journals 4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Caroline Camaré ◽  
Corinne Vanucci-Bacqué ◽  
Nathalie Augé ◽  
Mélanie Pucelle ◽  
Corinne Bernis ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neutral Type ◽  
Intraplaque Hemorrhage ◽  
Atherosclerotic Lesions ◽  
Plaque Development ◽  
Pathway Activation ◽  
Close Relationship ◽  
Sphingosine 1 Phosphate ◽  
Angiogenic Effect

The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs) contribute to the formation of tubesviathe generation of sphingosine 1-phosphate (S1P), a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE), an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM) elicited the formation of tubes by human microvascular endothelial cells (HMEC-1), whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1) pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.

scholarly journals Establishment of a Novel Mouse Model for Atherosclerotic Vulnerable Plaque

2021 ◽  
Vol 8 ◽  
Author(s):  
Xueyu Wang ◽  
Yahong Fu ◽  
Zulong Xie ◽  
Muhua Cao ◽  
Wenbo Qu ◽  
...  
Keyword(s):  
Vulnerable Plaque ◽  
Plaque Rupture ◽  
Fold Increase ◽  
Cell Number ◽  
Intraplaque Hemorrhage ◽  
Aortic Sinus ◽  
Coronary Syndrome ◽  
Atherosclerotic Lesions ◽  
Unstable Plaques ◽  
Novel Model

Background and Aims: Acute coronary syndrome (ACS) is a group of clinical syndromes characterized by rupture or erosion of atherosclerotic unstable plaques. Effective intervention for vulnerable plaques (VP) is of great significance to reduce adverse cardiovascular events.Methods: Fbn1C1039G+/− mice were crossbred with LDLR−/− mice to obtain a novel model for atherosclerotic VP. After the mice were fed with a high-fat diet (HFD) for 12 or 24 weeks, pathological staining and immunohistochemistry analyses were employed to evaluate atherosclerotic lesions.Results: Compared to control mice, Fbn1C1039G+/−LDLR−/− mice developed more severe atherosclerotic lesions, and the positive area of oil red O staining in the aortic sinus was significantly increased after 12 weeks (21.7 ± 2.0 vs. 6.3 ± 2.1) and 24 weeks (32.6 ± 2.5 vs. 18.7 ± 2.6) on a HFD. Additional vulnerable plaque characteristics, including significantly larger necrotic cores (280 ± 19 vs. 105 ± 7), thinner fiber caps (14.0 ± 2.8 vs. 32.6 ± 2.7), apparent elastin fiber fragmentation and vessel dilation (3,010 ± 67 vs. 1,465 ± 49), a 2-fold increase in macrophage number (8.5 ± 1.0 vs. 5.0 ± 0.6), obviously decreased smooth muscle cell number (0.6 ± 0.1 vs. 2.1 ± 0.2) and an ~25% decrease in total collagen content (33.6 ± 0.3 vs. 44.9 ± 9.1) were observed in Fbn1C1039G+/−LDLR−/− mice compared with control mice after 24 weeks. Furthermore, spontaneous plaque rupture, neovascularization, and intraplaque hemorrhage were detected in the model mouse plaque regions but not in those of the control mice.Conclusions: Plaques in Fbn1C1039G+/−LDLR−/− mice fed a HFD show many features of human advanced atherosclerotic unstable plaques. These results suggest that the Fbn1C1039G+/−LDLR−/− mouse is a novel model for investigating the pathological and physiological mechanisms of advanced atherosclerotic unstable plaques.

The Cellular Origin in Atheromatous Lesion

1970 ◽  
Vol 28 ◽  
pp. 202-203
Author(s):  
T. M. Murad ◽  
H. A. I. Newman ◽  
K. F. Kern
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Rabbit Aorta ◽  
Mixed Population ◽  
The Other ◽  
Cellular Origin ◽  
Ultrastructural Studies ◽  
Atherosclerotic Lesions ◽  
Show Evidence ◽  
Early Lesion

The origin of lipid containing cells in atheromatous lesion has been disputed. Geer in his study on atheromatous lesions of rabbit aorta, suggested that the early lesion is composed mainly of lipid-laden macrophages and the later lesion has a mixed population of macrophages and smooth muscle cells. Parker on the other hand, was able to show evidence that the rabbit lesion is primarily composed of lipid-laden cells of smooth muscle origin. The above studies and many others were done on an intact lesion without any attempt of cellular isolation previous to their ultrastructural studies. Cell isolation procedures have been established for atherosclerotic lesions through collagenase and elastase digestion Therefore this procedure can be utilized to identify the cells involved in rabbit atheroma.

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