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Transforming Growth Factor-?1 Inhibits Pseudoaneurysm Formation After Aortic Patch Angioplasty.

ABSTRACT: OBJECTIVE:Pseudoaneurysms remain a significant complication after vascular procedures. We hypothesized that TGF-? (transforming growth factor-?) 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-?1 receptors were increased in small pseudoaneurysms and preserved in large pseudoaneurysms. Delivery of TGF-?1 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-?1 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-?1 signaling, and recruitment of smad2 signaling may limit pseudoaneurysm formation; loss of TGF-?1 signaling is associated with the formation of large pseudoaneurysms. Enhancement of TGF-?1 signaling may be a potential mechanism to limit pseudoaneurysm formation after vascular intervention.

SUBMITTER: Bai H

PROVIDER: S-EPMC5746454 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

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