Endothelial transcriptomic changes induced by oxidized low density lipoprotein disclose an up-regulation of Jak–Stat pathway

ox‐LDL increases microRNA‐29a transcription through upregulating YY1 and STAT1 in macrophages

“…Our previous study (Yan et al, ) has identified the activity of JAK1/2 kinases was upregulated in ox‐LDL‐stimulating dendritic cell and responsible for the increased expression of YY1. Other researchers demonstrated that STAT1 was involved in the JAK1/2 kinases pathway in ox‐LDL‐stimulated endothelial cells (Maziere et al, ; Laguna‐Fernández et al, ). Thus, we speculated that the increased expression of miR‐29a by YY1 and STAT1 may be through JAK1/2 kinases pathway.…”

“…Recently, He et al () showed that STAT1 deletion alleviated inflammation of the arterial wall and decreased plaque burden through PDGFRβ pathway. Laguna‐Fernández et al () found that the upregulation of JAK‐STAT pathway induced endothelial transcriptomic changes after ox‐LDL treatment. Our study found that YY1 could directly bind to the promoter region of miR‐29a, and YY1 and STAT1 upregulation and translocation in the nucleus activated the transcription of miR‐29a through JAK1/2 pathway.…”

Oxidized LDLs as Signaling Molecules

“…However, as described here ( Figure 3 ), oxLDLs can function as signaling molecules at distant sites and are likely to play an important role in maintaining the systemic response to oxidative damage. Furthermore, oxLDL-induced changes in the interactome network could serve as biomarkers to follow the physio/pathological relevance of these signaling events [ 175 , 220 ]. In conclusion, as has happened with other “bad” molecules (e.g., amyloid-beta) [ 221 ], future studies may reveal that oxLDLs have hormetic effects, being useful in low concentrations and harmful in high quantities.…”

Pro‐atherogenic actions of signal transducer and activator of transcription 1 serine 727 phosphorylation in LDL receptor deficient mice via modulation of plaque inflammation

“…56 In addition, transcriptomic analysis of oxLDL stimulated endothelial cells revealed upregulation of STAT1 pathway. 57 The key role of STAT1 signaling was also suggested by data mining of atherosclerotic plaque transcriptomes 15 or by differential gene expression analysis of macrophages in atherosclerotic plaques informed by pathways identified via genome-wide association studies. 14 Suppressor of cytokine signaling-1-derived peptides, which inhibit both STAT-1 and -3 activation, improved inflammation and atherosclerosis in diabetic mice 58 so this represents one possible therapeutic avenue.…”

“…STAT1 signaling goes beyond IFN‐γ actions; for example, blockade of the cytokine tumor necrosis factor‐like weak inducer of apoptosis also reduced atherosclerotic lesion size and progression via inhibition of STAT1 signaling in diabetic mice 56 . In addition, transcriptomic analysis of oxLDL stimulated endothelial cells revealed upregulation of STAT1 pathway 57 . The key role of STAT1 signaling was also suggested by data mining of atherosclerotic plaque transcriptomes 15 or by differential gene expression analysis of macrophages in atherosclerotic plaques informed by pathways identified via genome‐wide association studies 14 .…”