From the Department of Vascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China (H.B.); Basic Medical College of Zhengzhou University, Henan, China (H.B., Y.X.); Vascular Biology and Therapeutics Program (H.B., H.H., T.W., T.I., S.L., J.G., H.L., K.W., S.O., X.G., B.Y., A.D.), Department of Surgery (H.B., H.H., T.W., T.I., S.L., J.G., H.L., K.W., S.O., X.G., B.Y., A.D.), and Department of Immunobiology (T.M.F.), Yale University School of Medicine, New Haven, CT; Department of Biomedical Engineering, Yale University, New Haven, CT (J.S.L., T.M.F.); and Department of Surgery, VA Connecticut Healthcare System, West Haven, CT (A.D.).
Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):195-205. doi: 10.1161/ATVBAHA.117.310372. Epub 2017 Nov 16.
Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-β (transforming growth factor-β) signaling plays a mechanistic role in the development of pseudoaneurysms.
Rat aortic pericardial patch angioplasty was associated with a high incidence (88%) of pseudoaneurysms at 30 days, with increased smad2 phosphorylation in small pseudoaneurysms but not in large pseudoaneurysms; TGF-β1 receptors were increased in small pseudoaneurysms and preserved in large pseudoaneurysms. Delivery of TGF-β1 via nanoparticles covalently bonded to the patch stimulated smad2 phosphorylation both in vitro and in vivo and significantly decreased pseudoaneurysm formation (6.7%). Inhibition of TGF-β1 signaling with SB431542 decreased smad2 phosphorylation both in vitro and in vivo and significantly induced pseudoaneurysm formation by day 7 (66.7%).
Normal healing after aortic patch angioplasty is associated with increased TGF-β1 signaling, and recruitment of smad2 signaling may limit pseudoaneurysm formation; loss of TGF-β1 signaling is associated with the formation of large pseudoaneurysms. Enhancement of TGF-β1 signaling may be a potential mechanism to limit pseudoaneurysm formation after vascular intervention.
血管手术后假性动脉瘤仍然是一个严重的并发症。我们假设 TGF-β（转化生长因子-β）信号在假性动脉瘤的发展中起机制作用。
大鼠主动脉心包补片血管成形术后 30 天假性动脉瘤的发生率很高（88%），小假性动脉瘤中 smad2 磷酸化增加，但大假性动脉瘤中 smad2 磷酸化没有增加；TGF-β1 受体在小假性动脉瘤中增加，在大假性动脉瘤中保留。通过共价结合到补片上的纳米颗粒递送 TGF-β1 在体外和体内均刺激 smad2 磷酸化，并显著降低假性动脉瘤形成（6.7%）。TGF-β1 信号抑制用 SB431542 降低了体外和体内的 smad2 磷酸化，并在第 7 天显著诱导假性动脉瘤形成（66.7%）。
主动脉补片血管成形术后的正常愈合与 TGF-β1 信号的增加有关，smad2 信号的募集可能限制假性动脉瘤的形成；TGF-β1 信号的丧失与大假性动脉瘤的形成有关。增强 TGF-β1 信号可能是限制血管介入后假性动脉瘤形成的潜在机制。
