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Arterioscler Thromb Vasc Biol. 2018 Jan;38(1):195-205. doi: 10.1161/ATVBAHA.117.310372. Epub 2017 Nov 16.

Transforming Growth Factor-β1 Inhibits Pseudoaneurysm Formation After Aortic Patch Angioplasty.

Author information

1
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.).
2
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.). alan.dardik@yale.edu.

Abstract

OBJECTIVE:

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.

APPROACH AND RESULTS:

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%).

CONCLUSIONS:

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.

KEYWORDS:

TGF beta; animal model; nanoparticle; pseudoaneurysm; smad2

PMID:
29146747
PMCID:
PMC5746454
DOI:
10.1161/ATVBAHA.117.310372
[Indexed for MEDLINE]
Free PMC Article

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