Animal Models of Neointimal Hyperplasia and Restenosis

Ebert, Max L.A.; Schmidt, Volker J.; Pfaff, Lena; Thaden, Anne von; Kimm, Melanie A.; Wildgruber, Moritz

doi:10.1016/j.jacbts.2021.06.006

Cited by 18 publications

(5 citation statements)

References 143 publications

(151 reference statements)

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“…Upon macroscopic examination, it was evident that the exterior diameter of the right common carotid artery had expanded significantly and the vascular wall had become considerably thickened and rigid and lost its elasticity (Figure I). Moreover, the intima of the right common carotid artery was thickened and uneven, and there was a substantial aggregation of macrophages and foam cells (Figure J), which was consistent with previous reports . The modeling success rate of this method was 85.7%.…”

Section: Resultssupporting

confidence: 90%

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Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis

Wen,

Fu,

Zhang

et al. 2024

ACS Appl. Mater. Interfaces

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophageaffinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn 0.4 Fe 2.6 O 4 ) as T 1 contrast agents were synthesized and modified with dopamine, 3,4dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T 1 relaxivity for different surface charged Zn 0.4 Fe 2.6 O 4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn 0.4 Fe 2.6 O 4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.

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Section: Resultssupporting

confidence: 90%

“…Moreover, the intima of the right common carotid artery was thickened and uneven, and there was a substantial aggregation of macrophages and foam cells (Figure 4J), which was consistent with previous reports. 48 The modeling success rate of this method was 85.7%. 5A).…”

Section: Rabbit Model Of Carotid Atherosclerotic Plaquementioning

confidence: 90%

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis

Wen,

Fu,

Zhang

et al. 2024

ACS Appl. Mater. Interfaces

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“…10,11,21 Unlike mice and pigs, rabbits have abundant plasma CETP activity which plays a significant role in human lipid metabolism. 40 Furthermore, considering the sensitivity to cholesterol diet of rabbits, we generated Lp-PLA 2 knockout rabbits using the CRISPR/Cas9 system to investigate the role of Lp-PLA 2 in lipid metabolism and atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Chen

Zhang

et al. 2023

ATVB

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Background: Elevated plasma Lp-PLA 2 (lipoprotein-associated phospholipase A 2 ) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA 2 is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA 2 could be a potential preventative target of atherosclerosis, we generated Lp-PLA 2 knockout rabbits and investigated the pathophysiological functions of Lp-PLA 2 . Methods: Lp-PLA 2 KO rabbits were generated using CRISPR/Cas9 system to assess the role of Lp-PLA 2 in plasma lipids regulation and identify its underlying molecular mechanisms. Homozygous knockout rabbits along with wild-type rabbits were fed a cholesterol-rich diet for up to 14 weeks and their atherosclerotic lesions were compared. Moreover, the effects of Lp-PLA 2 deficiency on the key cellular behaviors in atherosclerosis were assessed in vitro. Results: When rabbits were fed a standard diet, Lp-PLA 2 deficiency led to a significant reduction in plasma lipids. The decreased protein levels of SREBP2 (sterol regulatory element-binding protein 2) and HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) in livers of homozygous knockout rabbits indicated that the cholesterol biosynthetic pathway was impaired with Lp-PLA 2 deficiency. In vitro experiments further demonstrated that intracellular Lp-PLA 2 efficiently enhanced SREBP2-related cholesterol biosynthesis signaling independently of insulin-induced genes ( INSIG s). When fed a cholesterol-rich diet, homozygous knockout rabbits exhibited consistently lower level of hypercholesterolemia, and their aortic atherosclerosis lesions were significantly reduced by 60.2% compared with those of wild-type rabbits. The lesions of homozygous knockout rabbits were characterized by reduced macrophages and the expression of inflammatory cytokines. Macrophages of homozygous knockout rabbits were insensitive to M1 polarization and showed reduced DiI-labeled lipoprotein uptake capacity compared with wild-type macrophages. Lp-PLA 2 deficiency also inhibited the adhesion between monocytes and endothelial cells. Conclusions: These results demonstrate that Lp-PLA 2 plays a causal role in regulating blood lipid homeostasis and Lp-PLA 2 deficiency protects against dietary cholesterol-induced atherosclerosis in rabbits. Lp-PLA 2 could be a potential target for the prevention of atherosclerosis.

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“…As discussed above, the DMSs embedded in the vessel wall continue alkalization and hydrogen bubbling, which cause the death of surrounding vascular cells and the release of cellular calcium and phosphorus components, thus forming a local environment rich in apoptotic and inflammatory signals and with phosphorus and calcium buildup. The endothelial dysfunction that is once occurred due to the rupture of endothelium and subendothelial space also recurs, e.g. , increased endothelial permeability and activation.…”

Section: Modification Of the Vascular Microenvironment After Stent Im...mentioning

confidence: 99%

Adaptation of Vascular Smooth Muscle Cell to Degradable Metal Stent Implantation

Xun

Chen

2023

ACS Biomater. Sci. Eng.

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Iron-, magnesium-, or zinc-based metal vessel stents support vessel expansion at the period early after implantation and degrade away after vascular reconstruction, eliminating the side effects due to the long stay of stent implants in the body and the risks of restenosis and neoatherosclerosis. However, emerging evidence has indicated that their degradation alters the vascular microenvironment and induces adaptive responses of surrounding vessel cells, especially vascular smooth muscle cells (VSMCs). VSMCs are highly flexible cells that actively alter their phenotype in response to the stenting, similarly to what they do during all stages of atherosclerosis pathology, which significantly influences stent performance. This Review discusses how biodegradable metal stents modify vascular conditions and how VSMCs respond to various chemical, biological, and physical signals attributable to stent implantation. The focus is placed on the phenotypic adaptation of VSMCs and the clinical complications, which highlight the importance of VSMC transformation in future stent design.

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Animal Models of Neointimal Hyperplasia and Restenosis

Abstract: Central Illustration

Cited by 18 publications

References 143 publications

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis

Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Adaptation of Vascular Smooth Muscle Cell to Degradable Metal Stent Implantation

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Animal Models of Neointimal Hyperplasia and Restenosis

Abstract: Central Illustration

Cited by 18 publications

References 143 publications

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis

Tailoring Zinc Ferrite Nanoparticle Surface Coating for Macrophage-Affinity Magnetic Resonance Imaging of Atherosclerosis

Lp-PLA 2 (Lipoprotein-Associated Phospholipase A 2 ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits

Adaptation of Vascular Smooth Muscle Cell to Degradable Metal Stent Implantation

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Product

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Lp-PLA ₂ (Lipoprotein-Associated Phospholipase A ₂ ) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits