Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization
Peter K. Henke 1 , Manu R. Varma 1 , K. Barry Deatrick1 , Nicholas A. Dewyer 1 , Erin M. Lynch1 , Andrea J. Moore1 , Derek A. Dubay 2 , Pasu Sukheepod1 , Charles G. Pearce1 , Gilbert R.Upchurch, Jr. 1 , Steven L. Kunkel3 , Michael G. Franz 2 , Thomas W
1 Jobst Vascular Research Laboratories, Section of Vascular Surgery; 2 Section of General Surgery, Department of Surgery; and 3 Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Summary
Early deep venous thrombosis (DVT) resolution is associatedwith neutrophil (PMN) influx. This study examined the role ofPMNs in thrombus neovascularization and vein wall injury afterDVT.A rat model of DVT by inferior vena cava (IVC) ligation wasperformed with control serum or rabbit anti-rat PMN serumadministered perioperatively with sacrifice at 2 and 7 days.At 2days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and1.4-fold higher femoral venous pressures by water manometry(P = .008) but no difference in thrombus neovascularization wasobserved. By 7 days, DVT sizes were similar, but vein wall injurypersisted in the neutropenic rats with a 2.0-fold increase in veinwall stiffness by microtensiometry (P < .05), as well as a 1.2-fold increased thickness (P = .04). Collagen and profibrotic growthfactors were significantly increased in neutropenic IVC at 7 days(all P < .05).Vein wall and intrathrombus uPA byWestern immunoblotting,and intrathrombus MMP-9 gelatinase activity were significantlyless in neutropenic rats than controls (P < .001). Conversely,MMP-2 was significantly elevated in neutropenic IVC at2 days after DVT. However, neutropenia induced 24 hours afterDVT formation resulted in no significant increase in vein wallstiffness or collagen levels at 7 days, despite 1.4-fold largerthrombi (P < .05). These data suggest a critical early role forPMN in post DVT vein wall remodeling. Keywords
Deep vein thrombosis, Animal models, tissue remodelling, leukocyte function / activation
DOI
http://dx.doi.org/10.1160/TH05-02-0099