Anti-inflammatory and Anti-thrombotic Efficacy of Targeted Ultrasound Microbubbles on LPS-induced HUVEC Cells

Sun, Jindong; Pan, Shijun; Yu, Huamin; Hu, Haiqiang; Sun, Yu; Yang, Zhijian; Hoffman, Robert M.; Yuan, Hong

doi:10.21873/anticanres.15291

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…An increased expression of ET-1 receptors has been found in inflammatory cells (macrophages, T lymphocytes) and in the smooth muscle fibers of the vessels. It has been suggested that foam cells and T-lymphocytes regulate a switch in expression from ETA to ETB-receptors in vascular endothelial smooth muscle fibers [45]. However, only in vitro data have reported that bosentan has the potential of suppressing inflammation through the modification of inflammatory agents like TNF-a and MCP-1 in models simulating atherosclerosis [46,47].…”

Section: Discussionmentioning

confidence: 99%

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

Stasinopoulou,

Kostomitsopoulos,

Kadoglou

2024

Preprint

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Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p&lt;0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p&lt;0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p&lt;0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p&lt;0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

Stasinopoulou,

Kostomitsopoulos,

Kadoglou

2024

Preprint

View full text Add to dashboard Cite

show abstract

“…An increased expression of ET-1 receptors has been found in inflammatory cells (macrophages, T lymphocytes) and in the smooth muscle fibers of the vessels. It has been suggested that foam cells and T-lymphocytes regulate a switch in expression from ET A to ET B receptors in vascular endothelial smooth muscle fibers [ 48 ]. However, only in vitro data have reported that bosentan has the potential of suppressing inflammation through the modification of inflammatory agents like TNF-a and MCP-1 in models simulating atherosclerosis [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study

Stasinopoulou,

Kostomitsopoulos,

Kadoglou

2024

IJMS

View full text Add to dashboard Cite

Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male ApoE−/− mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, p < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG (p < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG (p < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG (p < 0.05). Bosentan treatment in diabetic, atherosclerotic ApoE−/− mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

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Anti-inflammatory and Anti-thrombotic Efficacy of Targeted Ultrasound Microbubbles on LPS-induced HUVEC Cells

Abstract: Materials and MethodsLigand conjugation of microbubbles. One vial (800 μL) of streptavidin-labeled ultrasound microbubbles (MBs) USphere™ Labeler-LS (TRUST Bio-sonics, Zhubei, Taiwan, ROC) was 4761 This article is freely accessible online.

Cited by 2 publications

References 25 publications

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

The Anti-atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin – an Experimental Study

The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin—An Experimental Study

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