Regulatory T cells protected against abdominal aortic aneurysm by suppression of the COX‐2 expression

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.

Mouse models for abdominal aortic aneurysm

“…An array of different inflammation modifying regimens have recently been reported to inhibit or promote the incidence and/or rupture of AAAs formed in the different mouse models (Figure 2 and Table S1) (Amin et al, 2019;Hiromi et al, 2020;Krishna et al, 2019;Li, Nie, et al, 2019;Li, Xia, et al, 2019;Liu, Fitzgerald, et al, 2019;Liu, Kong, et al, 2019;Nie et al, 2019;Paige et al, 2019;Peshkova et al, 2019;Ren et al, 2020;Sharma, Dev, Belenchia, et al, 2019;Suehiro et al, 2019;Suh et al, 2020). The nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain-containing receptor 3 (NLRP3)-inflammasome plays an important role in innate immunity through controlling the secretion of pro-inflammatory cytokines.…”

“…A large body of published research suggests that Foxp3 + regulatory T cells inhibit AAA development within both the angiotensin II and CaCl 2 models (Golledge, 2019;Liu, Kong, et al, 2019;Suh et al, 2020;Yodoi et al, 2015). Of potential clinical application, it was recently reported that ex vivo expansion and administration of Foxp3 + regulatory enriched T cells reduced the size of CaCl 2 -induced AAAs (Suh et al, 2020).…”

“…CD95L deficiency was associated with caspase-8 deficiency, which is believed to play an important role in activation of the NLRP3 inflammasome through cleaving pro-IL-1β (Liu, Kong, et al, 2019).…”

Prenatal High‐Sucrose Diet Induced Vascular Dysfunction in Thoracic Artery of Fetal Offspring

“…[ 9 ] Notably, alteration of AII receptors or/and the down‐stream signaling could increase the risk in many important processes underlying vascular injury in cardiovascular diseases. [ 10–14 ] Therefore, AII was used to test the basic vascular function in the present study. Ca 2+ is an important factor to regulate vascular contractions following stimulation of AII.…”

Patent Highlights December 2019–January 2020

“…Ruptures are fatal in 80% of cases and associated with extreme disability if survived [19]. No specific pharmacological treatment is available during the asymptomatic stage, although COX-2 inhibitors could be expected to have some effect on aneurysm growth and in preventing or delaying wall dissection [20,21]. The inventors have shown increased expression of tyrosine hydroxylase (the rate-limiting enzyme in catecholamine synthesis) in samples of patients with abdominal aortic aneurysm.…”