Non-activatable mutant of inhibitor of kappa B kinase α (IKKα) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice

Tilstam, Pathricia V.; Soppert, Josefin; Hemmers, Christian; Harlacher, Eva; Döring, Yvonne; Vorst, Emiel P. C. van der; Schulte, C.; Alampour-Rajabi, Setareh; Theelen, Wendy; Asare, Yaw; Winther, Menno P.J. de; Lawrence, Toby; Bernhagen, Jürgen; Schober, Andreas; Zernecke, Alma; Jankowski, Joachim; Noels, Heidi

doi:10.1016/j.atherosclerosis.2019.10.023

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…The kinases phosphorylate the inhibitory protein IκBα leading to its degradation and to ensuing activation of NF-κB. Tilstam et al [84] studied the effect of knock-in of an activation-resistant mutant of IKKα on atherosclerosis in apolipoprotein E (apoE) -deficient mice. IKKα AA/AA ApoE − /− and IKKα +/+ ApoE − /− littermate controls were fed a Western diet for 13 weeks.…”

Section: Vascular Biologymentioning

confidence: 99%

The year 2020 in Atherosclerosis

Binder¹,

Borén²,

Catapano³

et al. 2021

Atherosclerosis

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Section: Vascular Biologymentioning

confidence: 99%

The year 2020 in Atherosclerosis

Binder¹,

Borén²,

Catapano³

et al. 2021

Atherosclerosis

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“…However, when blood vessels are damaged or stimulated, SMC is converted into a synthetic phenotype that is hypertrophic and promotes proliferation and migration, and reduces vascular compliance (Mathieu et al, 2020). Pathology-based studies have also documented that synthetic SMC dominates in the fibrous caps of atherosclerotic plaques and create fibrous caps that are thinner and more unstable; collectively, these features can result in an acute coronary event (Tilstam et al, 2020). Maintaining the contractile phenotype of SMC and stabilizing the extracellular matrix (ECM) are important factors when considering how to stabilize atherosclerotic plaques.…”

Section: Introductionmentioning

confidence: 99%

ShenLian Extract Enhances TGF-β Functions in the Macrophage-SMC Unit and Stabilizes Atherosclerotic Plaques

Liu

Yin

et al. 2021

Front. Pharmacol.

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Background/Aim: Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques.Methods: The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE−/− mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining.Results: Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE−/− mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL.Conclusion: Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability.

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LncRNA TUG1 silencing enhances proliferation and migration of ox-LDL-treated human umbilical vein endothelial cells and promotes atherosclerotic vascular injury repairing via the Runx2/ANPEP axis

Yang

Zhang

et al. 2021

International Journal of Cardiology

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Non-activatable mutant of inhibitor of kappa B kinase α (IKKα) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice

Cited by 4 publications

References 45 publications

The year 2020 in Atherosclerosis

The year 2020 in Atherosclerosis

ShenLian Extract Enhances TGF-β Functions in the Macrophage-SMC Unit and Stabilizes Atherosclerotic Plaques

LncRNA TUG1 silencing enhances proliferation and migration of ox-LDL-treated human umbilical vein endothelial cells and promotes atherosclerotic vascular injury repairing via the Runx2/ANPEP axis

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