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

Peter K. Henke; Manu R. Varma; K. Barry Deatrick; Nicholas A. Dewyer; Erin M. Lynch; Andrea J. Moore; Derek A. Dubay; Pasu Sukheepod; Charles G. Pearce; Gilbert R. Upchurch Jr.; Steven L. Kunkel; Michael G. Franz; Thomas W. Wakefield

doi:10.1160/TH05-02-0099

Thrombosis and Haemostasis, Table of Contents

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

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Manu R. Varma

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

K. Barry Deatrick

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Nicholas A. Dewyer

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Erin M. Lynch

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Andrea J. Moore

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Derek A. Dubay

²Section of General Surgery, Department of Surgery

,

Pasu Sukheepod

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Charles G. Pearce

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Gilbert R. Upchurch Jr.

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

,

Steven L. Kunkel

³Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA

,

Michael G. Franz

²Section of General Surgery, Department of Surgery

,

Thomas W. Wakefield

¹Jobst Vascular Research Laboratories, Section of Vascular Surgery

› Author Affiliations

Abstract

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

Full Text

References

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