Neutrophils modulate post-thrombotic vein wall remodeling but not thrombus neovascularization.
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. By 7 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 as a 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors 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 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.
Henke
Peter K
PK
University of Michigan Health System, 1500 E. Medical Center Drive, 2210 Taubman Health Care Center, Ann Arbor, MI 48109-0329 USA. henke@umich.edu
Varma
Manu R
MR
Deatrick
K Barry
KB
Dewyer
Nicholas A
NA
Drewyer
Nicholas A
NA
Lynch
Erin M
EM
Moore
Andrea J
AJ
Dubay
Derek A
DA
Sukheepod
Pasu
P
Pearce
Charles G
CG
Upchurch
Gilbert R
GR
Kunkel
Steven L
SL
Franz
Michael G
MG
Wakefield
Thomas W
TW
D000818:Animals; D003094:Collagen / Q000032:analysis; D006133:Growth Substances / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D018919:Neovascularization, Physiologic; D009503:Neutropenia; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D014680:Veins / Q000502:physiology*; D020246:Venous Thrombosis / Q000473:pathology*
D006133:Growth Substances; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9