Induction of the Coxsackievirus and Adenovirus Receptor in Macrophages During the Formation of Atherosclerotic Plaques

Abstract

<jats:title>Abstract</jats:title> <jats:p>Multiple viruses are implicated in atherosclerosis but the mechanisms of how they infect cells and contribute to plaque formation in arterial walls are not well understood. Based on reports showing the presence of enterovirus in atherosclerotic plaques we hypothesized that the coxsackie- and adenovirus receptor (CXADR), although absent in normal arteries, could be induced during plaque formation. Large-scale microarray and mass-spectrometry analyses revealed significant upregulation of CXADR mRNA and protein levels in plaque-invested carotid arteries compared to control arteries. Macrophages were identified as a previously unknown cellular source of CXADR in human plaques and plaques from Ldr-/- Apob100/100 mice. CXADR specifically associated with M1-polarized macrophages and foam cells and was experimentally induced during macrophage differentiation. Furthermore, CXADR significantly correlated with receptors for other viruses linked to atherosclerosis. The results show that CXADR is induced in macrophages during plaque formation, suggesting a mechanism by which enterovirus infect cells in atherosclerotic plaques.</jats:p>

Roles of Macrophages in Atherogenesis

“…The enterovirus receptor CXADR is upregulated in Mφs in atherosclerotic plaques. CXADR expression was associated with M1 Mφ polarization and foam cells formation, suggesting a mechanism by which enterovirus may infect the cells in atherosclerotic lesions (Nilchian et al, 2020).…”

Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity

“…Hexon is the most abundant capsid protein of Ad5 and is the main target of Ad5-neutralizing antibodies (Nabs) [36] . In contrast to the HeLa and A549 cells, the 3T3 cells and THP-1 do not express CAR [37] , [38] , [39] . These findings were consistent with the observations that the transgene expression of Ad5-luc in 3T3 cells and THP-1 was much lower than that in HeLa and A549 cells ( Fig.…”

Activation of Annexin A2 signaling at the blood–brain barrier in a mouse model of multiple sclerosis

“…During inflammation, CXADR is up-regulated in migratory cells and has been shown to be significantly up-regulated in macrophages at the mRNA and protein levels (Nilchian et al, 2020). In the present study, the isolated vascular fraction did not contain blood cells because the vessels were perfused with PBS immediately before the isolation of the brain capillaries.…”

“…In contrast, it appears that the expression of CXADR (3.5‐fold), which along with ESAM, CADM, and HEPECAM, are members of the IgSFCAM family, was increased for the first time (Figure 3b). During inflammation, CXADR is up‐regulated in migratory cells and has been shown to be significantly up‐regulated in macrophages at the mRNA and protein levels (Nilchian et al, 2020). In the present study, the isolated vascular fraction did not contain blood cells because the vessels were perfused with PBS immediately before the isolation of the brain capillaries.…”