Abstract
CD4+CD25+ regulatory T cells (Tregs) have been shown to protect against the development of abdominal aortic aneurysm (AAA). Cyclooxygenase‐2 (COX‐2), a pro‐inflammatory protein, can convert arachidonic acid into prostaglandins (PGs). The present study was aimed to investigate the effect of Tregs on COX‐2 expression in angiotension II (Ang II)‐induced AAA in ApoE−/− mice. Tregs were injected via tail vein in every 2 weeks. Ang II was continuously infused by a micropump for 28 days to induce AAA. In vivo, compared with the control group, adoptive transfer of Tregs significantly reduced the incidence of AAA, maximal diameter, and the mRNA and protein expression of COX‐2 in mice. Immunofluorescence showed that Tregs treatment reduced COX‐2 expression both in smooth muscle cells (SMCs) and macrophages in AAA. In vitro, the Western blot analysis showed that Tregs reduced Ang II‐induced COX‐2 expression in macrophages and SMCs. Meanwhile, ELISA showed that Tregs reduced Ang II‐induced prostaglandin E2 (PGE2) secretion. Moreover, Tregs increased SMC viability and induced transition of macrophages phenotype from M1 to M2. In conclusion, Tregs treatment dramatically decreased the expression of COX‐2 in vivo and in vitro, suggesting that Tregs could protect against AAA through inhibition of COX‐2. The study may shed light on the immune treatment of AAA.
Highlights
Abdominal aortic aneurysm (AAA), as a chronic vascular degener‐ ative disease, is characterized with a progressive dilation and re‐ modelling of the vessel wall, leading to a lethal risk of aortic rupture, especially in the elderly.[1,2] the pathogenesis of AAA is still not fully explained
We found that the expression of COX‐2 and prostaglandin E2 (PGE2) was markedly reduced by Tregs treatment as compared with the control group, while CD4+CD25− T cells had no effect on COX‐2 and PGE2 expression (P < 0.05, Figure 4A‐C)
The results showed that Tregs therapy reduced angiotension II (Ang II)‐induced COX‐2 and PGE2 expression both in macrophages and smooth muscle cells (SMCs)
Summary
Abdominal aortic aneurysm (AAA), as a chronic vascular degener‐ ative disease, is characterized with a progressive dilation and re‐ modelling of the vessel wall, leading to a lethal risk of aortic rupture, especially in the elderly.[1,2] the pathogenesis of AAA is still not fully explained. It has been demonstrated that immune system took part in the pathogenesis of many cardiovascular diseases.[12] CD4+CD25+ reg‐ ulatory T cells (Tregs), as an important component of the immune system, maintained immunological homeostasis and tolerance, and prevented excessive immune responses.[13] An impaired function or a deficiency of Tregs can result in immune dysregulation and autoim‐ mune disease.[13] It has been documented that Tregs have a protec‐ tive role in many cardiovascular disease, including atherosclerosis, hypertension, myocarditis and dilated cardiomyopathy.[14] Recently, Tregs have been showed to prevent the development of Ang II‐in‐ duced AAA in mice.[15,16]. By use of an AAA model, we attempt to investigate the potential mechanism and look for an immune treatment of AAA
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