Abstract:
BACKGROUND:Loss of critical endothelial cell function and subsequent vascular smooth muscle cell (VSMC) migration is central to the pathology of injury-induced neointimal hyperplasia and recurrent stenosis. Thrombomodulin (TM), well known for its function as an endothelial surface anticoagulant, may have an unknown direct effect on VSMC physiology that would be lost after injury. Here, we examined a novel effect of TM on VSMC by testing the hypothesis that direct application of TM induces favorable changes to the morphology of VSMC and inhibits their migration. METHODS:Primary human VSMC were harvested using the explant technique and used in early passage (1-4) for all experiments. Laser-scanning confocal fluorescent imaging was performed to assess the effect of soluble TM on VSMC morphology. In vitro, migration of VSMC was measured using: (1) a 4-hr modified Boyden chemotaxis assay and (2) a 24-hr electric cell-substrate impedance sensing injury migration assay. Migration experiments were conducted with VSMC exposed to increasing doses of soluble recombinant TM. Recombinant thrombin served as a positive control and serum-free media as a negative control for all experimentation. Data were analyzed using a Student's t-test or repeated measures analysis of variance where appropriate (α < 0.05). RESULTS:VSMC exposed to TM clearly demonstrated a quiescent morphology with organized stress fibers consistent with a quiescent, differentiated, contractile phenotype; whereas, thrombin stimulation led to an activated, dedifferentiated, synthetic phenotype. VSMC demonstrated a low, baseline level of migration in unstimulated serum-free conditions. Thrombin significantly stimulated VSMC migration as expected. TM, independent of thrombin, significantly inhibited baseline VSMC migration in a dose-response fashion. The maximal inhibition was observed at (5 μg/mL) with 70% reduction (56 ± 1.7 vs. 18 ± 3.5 cells/5 high-power fields, P = 0.0005). CONCLUSIONS:TM has a direct effect on VSMC resulting in a quiescent, differentiated and contractile phenotype, and inhibition of migration. This effect is independent of the presence of thrombin. These findings provide new knowledge in understanding the pathophysiology of vascular injury and support a strategy focused on restoring key endothelial function to prevent intimal hyperplasia.
journal_name
Ann Vasc Surgjournal_title
Annals of vascular surgeryauthors
Bass HM,Beard RS Jr,Cha BJ,Yuan SY,Nelson PRdoi
10.1016/j.avsg.2015.10.002subject
Has Abstractpub_date
2016-01-01 00:00:00pages
149-56eissn
0890-5096issn
1615-5947pii
S0890-5096(15)00776-1journal_volume
30pub_type
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journal_title:Annals of vascular surgery
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journal_title:Annals of vascular surgery
pub_type: 杂志文章,评审
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abstract::Cases of malignant fibrous histiocytoma arising from the aorta are rare and have a dismal outlook despite treatment. The longest reported survival period following resection is only 28 months. A patient with malignant fibrous histiocytoma of the descending thoracic aorta was successfully treated with resection and rec...
journal_title:Annals of vascular surgery
pub_type: 杂志文章
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2016.10.066
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journal_title:Annals of vascular surgery
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doi:10.1016/j.avsg.2016.08.028
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journal_title:Annals of vascular surgery
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2020.11.024
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2019.01.006
更新日期:2019-07-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1007/s10016-001-0184-7
更新日期:2002-05-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1007/s10016-001-0336-9
更新日期:2003-01-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1007/s10016-006-9089-9
更新日期:2006-11-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2017.10.004
更新日期:2018-05-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章,评审
doi:10.1007/BF02000153
更新日期:1993-11-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2011.06.002
更新日期:2011-10-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
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更新日期:2017-07-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2017.04.033
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2010.07.016
更新日期:2011-02-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1007/s10016-001-0057-0
更新日期:2002-03-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1007/s10016-003-0031-0
更新日期:2003-07-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2018.01.083
更新日期:2018-07-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1016/j.avsg.2013.03.005
更新日期:2013-10-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type:
doi:10.1016/j.avsg.2020.07.020
更新日期:2020-11-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
doi:10.1007/BF02016753
更新日期:1991-03-01 00:00:00
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journal_title:Annals of vascular surgery
pub_type: 杂志文章
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更新日期:2005-11-01 00:00:00
abstract:BACKGROUND:Controversies on chemical venous thromboembolic (VTE) prophylaxis in patients undergoing lung resection for malignancy exist. The available guidelines on VTE do not specifically address its prophylaxis in patients undergoing oncologic lung resections. The goal of this survey was to evaluate the perception of...
journal_title:Annals of vascular surgery
pub_type: 杂志文章
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更新日期:2017-10-01 00:00:00