Abdominal aortic aneurysm (AAA) is a fatal vascular disease with insidious symptoms. However, the mechanism behind its development remains unclear. The transient receptor potential vanilloid (TRPV) family has crucial protective effects against cardiovascular diseases, but the role of TRPV5 in AAA has yet to be reported. In this study, ApoE^−/− mice were intraperitoneally injected with AAV-GFP or AAV-TRPV5. After 30 days, mice were further administered with angiotensin II (Ang II, 1.44 mg/kg/day) by using osmotic pumps to induce the AAA model or Saline for 28 days, (i.e., Saline + AAV-GFP, Saline + AAV-TRPV5, Ang II + AAV-GFP and Ang II + AAV-TRPV5 groups were established). Compared with the control group, the incidence of AAA and the maximal diameter of the abdominal aorta markedly decreased in Ang II + AAV-TRPV5, which was detected by vascular ultrasound at 28 day. Meanwhile, less collagen and elastin degradation were observed in the Ang II + AAV-TRPV5 group by using Masson and Elastin stains. Moreover, more α-SMA and less MMP2 was observed in the abdominal aortas collected at 28 day by immunohistochemistry. In vitro, primary mouse vascular smooth muscle cells (VSMCs) were treated with Ang II (1 μM) to induce phenotype switch. Sh-TRPV5 and AdTRPV5 were used to transfect VSMCs. PCR and Western blotting were used to access the expression of contractile marker, including α-SMA and SM-22α. The results showed that the mRNA and protein level of α-SMA and SM-22α were decreased under the stimulation of Ang II, but could be attenuated by TRPV5 overexpression. The cell scratch assay demonstrated that the migration ability of VSMCs was increased in Ang II treated group and could be ameliorated by TRPV5 overexpression. Above all, VSMCs transformed from the contractile into secretory phenotype under Ang II stimuli, but could be rescued by TRPV5 overexpression. Furthermore, TRPV5 overexpression suppressed the increased expression of KLF4 induced by Ang II treatment in VSMCs. The data demonstrated that TRPV5 could inhibit AAA formation and play a critical role in the VSMC phenotype switch by downregulating KLF4, suggesting TRPV5 as a new strategy for treating AAA.

腹主动脉瘤（AAA）是一种致命的血管疾病，具有隐匿性症状。但是，其发展背后的机制仍不清楚。暂时性受体电位香草类（TRPV）家族对心血管疾病具有至关重要的保护作用，但尚未报道TRPV5在AAA中的作用。在这项研究中，ApoE ^-/-腹膜内注射AAV-GFP或AAV-TRPV5。30天后，通过使用渗透泵诱导AAA模型或生理盐水28天（即生理盐水+ AAV-GFP，生理盐水+ AAV--）进一步向小鼠施用血管紧张素II（Ang II，1.44 mg / kg /天）建立了TRPV5，Ang II + AAV-GFP和Ang II + AAV-TRPV5组。与对照组相比，Ang II + AAV-TRPV5中AAA的发生率和腹主动脉最大直径明显减少，这是在28天时通过血管超声检测到的。同时，通过使用Masson和Elastin染色剂，在Ang II + AAV-TRPV5组中观察到较少的胶原蛋白和弹性蛋白降解。此外，通过免疫组织化学观察，在第28天收集的腹主动脉中观察到更多的α-SMA和更少的MMP2。体外，用Ang II（1μM）处理小鼠原代血管平滑肌细胞（VSMC），以诱导表型转换。Sh-TRPV5和AdTRPV5用于转染VSMC。PCR和Western blotting用于检测包括α-SMA和SM-22α在内的收缩标志物的表达。结果表明，在Ang II刺激下，α-SMA和SM-22α的mRNA和蛋白水平降低，但可能被TRPV5的过表达所减弱。细胞刮擦试验表明，Ang II处理组中VSMC的迁移能力增加，并且TRPV5过表达可以改善其迁移能力。最重要的是，VSMCs在Ang II刺激下从收缩型转变为分泌型，但可以通过TRPV5的过表达来挽救。此外，TRPV5过表达抑制了VSMC中Ang II处理诱导的KLF4表达增加。数据表明，TRPV5可以通过下调KLF4抑制AAA的形成并在VSMC表型转换中起关键作用，这表明TRPV5是治疗AAA的新策略。