intraplaque angiogenesis

Vein grafting is a frequently used surgical intervention for cardiac revascularization. However, vein grafts display regions with intraplaque (IP) angiogenesis, which promotes atherogenesis and formation of unstable plaques. Graft neovessels are mainly composed of endothelial cells (ECs) that largely depend on glycolysis for migration and proliferation. In the present study, we aimed to investigate whether loss of the glycolytic flux enzyme phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) in ECs inhibits IP angiogenesis and as such prevents unstable plaque formation...

BACKGROUND: Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68 Ga-NODAGA-RGD, a specific αv β3 integrin ligand for PET. MATERIALS AND METHODS: The data of 44 patients who underwent 68 Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed...

Pathological angiogenesis is a crucial factor that causes atherosclerotic plaque rupture. Sinoporphyrin sodium-mediated sonodynamic therapy (DVDMS-SDT) induces regression of plaque neovascularization in humans without causing obvious side effects. However, a clinical noninvasive theranostic strategy for atherosclerotic plaque neovascularization is urgently needed. A nanoplatform designed for multimodality imaging-guided SDT in plaque angiogenesis theranostics, termed PFP-HMME@PLGA/MnFe2 O4 -ramucirumab nanoparticles (PHPMR NPs), is fabricated...

BACKGROUND: Growing experimental evidence has identified neovascularization from the adventitial vasa vasorum and induced intraplaque hemorrhage (IPH) as critical indicators during the development of vulnerable atherosclerotic plaques. In this study, we propose a mathematical model incorporating intraplaque angiogenesis and hemodynamic calculation of the microcirculation, to obtain the quantitative evaluation of the influences of intraplaque neovascularization and hemorrhage on vulnerable plaque development...

The vascular endothelium is a highly specialized barrier that controls passage of fluids and migration of cells from the lumen into the vessel wall. Endothelial cells assist leukocytes to extravasate and despite the variety in the specific mechanisms utilized by different leukocytes to cross different vascular beds, there is a general principle of capture, rolling, slow rolling, arrest, crawling, and ultimately diapedesis via a paracellular or transcellular route. In atherosclerosis, the barrier function of the endothelium is impaired leading to uncontrolled leukocyte extravasation and vascular leakage...

OBJECTIVE: Statins pleiotropically provide additional benefits in reducing atherosclerosis, but their effects on intraplaque angiogenesis (IPA) and hemorrhage (IPH) remain unclear. Therefore, we discriminated statin's lipid-lowering dependent and independent effects on IPA and IPH. APPROACH AND RESULTS: ApoE3*Leiden mice are statin-responsive due to ApoE and LDLR presence, but also allow to titrate plasma cholesterol levels by diet. Therefore, ApoE3*Leiden mice were fed a high-cholesterol-inducing-diet (HCD) with or without atorvastatin (A) or a moderate-cholesterol-inducing-diet (MCD)...

Combination of antiangiogenesis and immunotherapy may be an effective strategy for treatment of solid tumors. Our previous work reported that activation of CD137 signaling promotes intraplaque angiogenesis. A number of studies have demonstrated that vascular endothelial growth factor receptor 2 (VEGFR2) is a key target for angiogenesis. However, it is unknown whether CD137-mediated angiogenesis is related to VEGFR2. In this study, we investigated the effect of CD137 on the VEGFR2 expression and explored the underlying mechanisms of CD137-mediated angiogenesis...

Atherosclerosis, calcific aortic valve disease (CAVD), and bioprosthetic heart valve degeneration (alternatively termed structural valve deterioration, SVD) represent three diseases affecting distinct components of the circulatory system and their substitutes, yet sharing multiple risk factors and commonly leading to the extraskeletal calcification. Whereas the histopathology of the mentioned disorders is well-described, their ultrastructural pathology is largely obscure due to the lack of appropriate investigation techniques...

Multiple lines of evidence suggest that intraplaque (IP) neovascularization promotes atherosclerotic plaque growth, destabilization, and rupture. However, pharmacological inhibition of IP neovascularization remains largely unexplored due to the limited number of animal models that develop IP neovessels and the lack of reliable methods for visualizing IP angiogenesis. Here, we applied 3D confocal microscopy with an optimized tissue-clearing process, immunolabeling-enabled three-dimensional imaging of solvent-cleared organs, to visualize IP neovessels in apolipoprotein E-deficient (ApoE-/-) mice carrying a heterozygous mutation (C1039+/-) in the fibrillin-1 gene...

AIMS: Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention with respect to atherosclerosis, since both KP-10 and GPR54 are expressed at high levels in atheromatous plaques and restenotic lesions after wire-injury. The present review introduces the emerging roles of the KP-10/GPR54 system in atherosclerosis. DATA SYNTHESIS: KP-10 suppresses migration and proliferation of human umbilical vein endothelial cells (HUVECs), and induces senescence in HUVECs...

OBJECTIVE: Intraplaque neovascularization is an important feature of unstable human atherosclerotic plaques. However, its impact on plaque formation and stability is poorly studied. Because proliferating endothelial cells generate up to 85% of their ATP from glycolysis, we investigated whether pharmacological inhibition of glycolytic flux by the small-molecule 3PO (3-[3-pyridinyl]-1-[4-pyridinyl]-2-propen-1-one) could have beneficial effects on plaque formation and composition. Approach and Results: ApoE-/ - (apolipoprotein E deficient) mice treated with 3PO (50 µg/g, ip; 4×/wk, 4 weeks) showed a metabolic switch toward ketone body formation...

During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture...

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...

This study aimed to explore the interactions among long non-coding RNA H19, transcriptional factor CCCTC-binding factor (CTCF) and polycystic kidney disease 1 (PKD1), and to investigate its potentially regulatory effect on vulnerable plaque formation and angiogenesis of atherosclerosis. We established an atherosclerosis mouse model in ApoE knockout mice, followed by gain- and loss-of-function approaches. H19 was upregulated in aortic tissues of atherosclerosis mice, but silencing of H19 significantly inhibited atherosclerotic vulnerable plaque formation and intraplaque angiogenesis, accompanied by a downregulated expression of MMP-2, VEGF, and p53 and an upregulated expression of TIMP-1...

OBJECTIVES: Intraplaque angiogenesis and inflammation are key promoters of atherosclerosis and are mediated by the alpha-V beta-3 (αv β3 ) integrin pathway. We investigated the applicability of the αv β3 -integrin receptor-selective positron emission tomography (PET) radiotracer 18F-fluciclatide in assessing human aortic atherosclerosis. METHODS: Vascular 18F-fluciclatide binding was evaluated using ex vivo analysis of carotid endarterectomy samples with autoradiography and immunohistochemistry, and in vivo kinetic modelling following radiotracer administration...

Progression of atherosclerotic plaques into life-threatening lesions is associated with angiogenesis which contributes to intraplaque hemorrhages and plaque instability. The lack of adequate models for the study of human plaque-induced angiogenesis has limited progress in this field. We describe here a novel ex vivo model which fills this gap. Plaques obtained from 15 patients who underwent endarterectomy procedures were co-cultured in collagen gels with rat aorta rings which served as read-out of human plaque angiogenic activity...

Coronary artery disease remains an important cause of morbidity and mortality. Previous work, including ours, has focused on the role of intraplaque hemorrhage, particularly from immature microvessel angiogenesis, as an important contributor to plaque progression via increases in vascular permeability leading to further intraplaque hemorrhage, which increases red cell membrane-derived free cholesterol in plaque content and inflammatory cell recruitment. Evans Blue Dye (EBD) assay is widely used as a standard assay for vasculature permeability...

Excessive neovascularization of atherosclerotic lesions increases plaque vulnerability and the susceptibility to rupture. Semaphorin 7A (Sema7A), a semaphorin family member, was recently reported to promote atherosclerotic plaque formation by mediating d-flow-induced endothelial phenotypic change and leukocyte adhesion. To extend our understanding of the proatherogenic role of Sema7A, we investigated the role of endothelial Sema7A in angiogenesis and atherosclerotic neovascularization. Sema7A overexpression in human umbilical vein endothelial cells (HUVECs) significantly upregulated VEGFA/VEGFR2 and promoted cell migration and angiogenesis...

We propose a multiphysical mathematical model by fully coupling lipid deposition, monocytes/macrophages recruitment and angiogenesis to investigate the pathophysiological responses of an atherosclerotic plaque to the dynamic changes in the microenvironment. The time evolutions of cellular (endothelial cells, macrophages, smooth muscle cells, etc.) and acellular components (low density lipoprotein, proinflammatory cytokines, extravascular plasma concentration, etc.) within the plaque microenvironment are assessed quantitatively...

BACKGROUND: Carotid endarterectomy (CEA) is known to reduce stroke risk in patients with symptomatic, moderate to severe carotid stenosis but has no apparent impact in patients with symptomatic, mild (less than 50%) carotid stenosis. However, recent development of noninvasive imaging modalities has shown that a certain subgroup of patients are at high risk for further ischemic events despite antiplatelet therapy. This study, therefore, aimed to clarify the patients' clinical features and explore the impact of CEA for them...