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Cardiovascular Drugs and Therapy
Erschienen in: Cardiovascular Drugs and Therapy 2/2022

18.01.2021 | Original Article

HIV Protein Tat Induces Macrophage Dysfunction and Atherosclerosis Development in Low-Density Lipoprotein Receptor–Deficient Mice

verfasst von: Zhaojie Meng, Rebecca Hernandez, Jingwei Liu, Taesik Gwag, Weiwei Lu, Tzung K Hsiai, Marcus Kaul, Tong Zhou, Changcheng Zhou

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 2/2022

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Abstract

Purpose

HIV infection is consistently associated with an increased risk of atherosclerotic cardiovascular disease, but the underlying mechanisms remain elusive. HIV protein Tat, a transcriptional activator of HIV, has been shown to activate NF-κB signaling and promote inflammation in vitro. However, the atherogenic effects of HIV Tat have not been investigated in vivo. Macrophages are one of the major cell types involved in the initiation and progression of atherosclerosis. We and others have previously revealed the important role of IκB kinase β (IKKβ), a central inflammatory coordinator through activating NF-κB, in the regulation of macrophage functions and atherogenesis. This study investigated the impact of HIV Tat exposure on macrophage functions and atherogenesis.

Methods

To investigate the effects of Tat on macrophage IKKβ activation and atherosclerosis development in vivo, myeloid-specific IKKβ-deficient LDLR-deficient (IKKβΔMyeLDLR−/−) mice and their control littermates (IKKβF/FLDLR−/−) were exposed to recombinant HIV protein Tat.

Results

Exposure to Tat significantly increased atherosclerotic lesion size and plaque vulnerability in IKKβF/FLDLR−/− but not IKKβΔMyeLDLR−/− mice. Deficiency of myeloid IKKβ attenuated Tat-elicited macrophage inflammatory responses and atherosclerotic lesional inflammation in IKKβΔMyeLDLR−/− mice. Further, RNAseq analysis demonstrated that HIV protein Tat affects the expression of many atherosclerosis-related genes in vitro in an IKKβ-dependent manner.

Conclusions

Our findings reveal atherogenic effects of HIV protein Tat in vivo and demonstrate a pivotal role of myeloid IKKβ in Tat-driven atherogenesis.
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Metadaten
Titel
HIV Protein Tat Induces Macrophage Dysfunction and Atherosclerosis Development in Low-Density Lipoprotein Receptor–Deficient Mice
verfasst von
Zhaojie Meng
Rebecca Hernandez
Jingwei Liu
Taesik Gwag
Weiwei Lu
Tzung K Hsiai
Marcus Kaul
Tong Zhou
Changcheng Zhou
Publikationsdatum
18.01.2021
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 2/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07141-x

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