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Thromb Haemost 2006; 95(02): 272-281
DOI: 10.1160/TH05-02-0099
Platelets and Blood Cells
Schattauer GmbH

Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization

Peter K. Henke
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Manu R. Varma
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
K. Barry Deatrick
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Nicholas A. Dewyer
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Erin M. Lynch
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Andrea J. Moore
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Derek A. Dubay
2   Section of General Surgery, Department of Surgery
,
Pasu Sukheepod
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Charles G. Pearce
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Gilbert R. Upchurch Jr.
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
,
Steven L. Kunkel
3   Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
,
Michael G. Franz
2   Section of General Surgery, Department of Surgery
,
Thomas W. Wakefield
1   Jobst Vascular Research Laboratories, Section of Vascular Surgery
› Author AffiliationsFinancial support: Supported by Lifeline Foundation, vonLeibig Foundation, and NIH K-08 HL#69780 (PKH) and HL #70766 (TWW).
Further Information

Publication History

Received 09 February 2005

Accepted after revision 16 January 2005

Publication Date:
28 November 2017 (online)

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Summary

Early deep venous thrombosis (DVT) resolution is associated with neutrophil (PMN) influx. This study examined the role of PMNs in thrombus neovascularization and vein wall injury after DVT. A rat model of DVT by inferior vena cava (IVC) ligation was performed with control serum or rabbit anti-rat PMN serum administered perioperatively with sacrifice at 2 and 7 days. At 2 days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and 1.4-fold higher femoral venous pressures by water manometry (P = .008) but no difference in thrombus neovascularization was observed. By7 days, DVT sizes were similar, but vein wall injury persisted in the neutropenic rats with a 2.0-fold increase in vein wall stiffness by microtensiometry (P< .05), as well asa 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors were significantly increased in neutropenic IVC at7 days (all P< .05).Vein wall and intrathrombus uPA by Western immunoblotting, and intrathrombus MMP-9 gelatinase activity were significantly less in neutropenic rats than controls (P < .001). Conversely, MMP-2 was significantly elevated in neutropenic IVC at 2 days after DVT. However, neutropenia induced 24 hours after DVT formation resulted in no significant increase in vein wall stiffness or collagen levels at 7 days, despite 1.4-fold larger thrombi (P < .05). These data suggest a critical early role for PMN in post DVT vein wall remodeling.

Keywords

Animal models - tissue remodelling - leukocyte function / activation - deep vein thrombosis

* Presented in part at the 65th Annual Meeting of the Society of University Surgeons, February 13, 2004, St. Louis, MO, USA.


 

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