Ramping up RANTES in the acute response to arterial injury
Timothy Hla, Myat Lin Oo
Timothy Hla, Myat Lin Oo
Published December 28, 2009
Citation Information: J Clin Invest. 2010;120(1):90-92. https://doi.org/10.1172/JCI41738.
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Commentary

Ramping up RANTES in the acute response to arterial injury

Abstract

Arterial injury results in the formation of neointimal lesions. Lack of resolution of the pathologic neointima leads to stenosis, tissue ischemia, and organ dysfunction. In this issue of the JCI, Kovacic et al. show that, in response to arterial injury in mice, the cytokine TNF-α triggers a novel signaling pathway involving the combinatorial action of two transcription factors, STAT3 and NF-κB (p65 subunit), in VSMCs (see the related article beginning on page 303). Upon activation, these factors turn on transcription of a potent T cell chemokine, RANTES, which selectively recruits T cells into the vessel wall as part of the vascular wound–healing response.

Authors

Timothy Hla, Myat Lin Oo

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Figure 1

Schematic representation of VSMC signaling mechanisms involved in T cell recruitment following acute arterial injury.

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Schematic representation of VSMC signaling mechanisms involved in T cell...
During vascular injury and deendothelialization, VSMC migration and activation recruits immune cells such as macrophages and T cells, resulting in the formation of a neointimal lesion. In their study in this issue of the JCI, Kovacic et al. show that TNF-α activation of TNF-α–R1 on VSMCs results in the stimulation of NF-κB (p65 subunit) and STAT3 pathways (9). The complexes formed by NF-κB, STAT3, and p21Cip1 are found in the activated, neointimal VSMCs. Combinatorial action of NF-κB and STAT3 turns on the transcription of the RANTES gene, which encodes the T cell chemokine RANTES (also known as CCL5). Secreted RANTES acts on its receptor, CCR5, on T cells to induce chemotaxis, thus allowing T cell entry into the neointimal lesion. TRADD, TNFRSF1A-associated via death domain.