Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi.
OBJECTIVE
Organization, recanalization, and contraction are common to wound healing and thrombus resolution. Monocytes are essential to wound healing and are also found in venous thrombi. We measured endogenous levels of the monocyte chemotactic protein-1 (MCP-1) in naturally resolving venous thrombi and determined the effect of injecting MCP-1 into newly formed thrombus.


METHODS
Endogenous MCP-1 levels were estimated in rat blood, thrombi, and the adjacent vessel wall after thrombus formation, in cohorts of eight animals at 1, 7, and 14 days. In another group (n = 10), 1 microgram of MCP-1 was injected into newly formed thrombi. Carrier was injected into the thrombi of control animals (n = 10). Thrombi and adjacent vein walls were obtained for histology at 7 days. Thrombi were given an arbitrary organization score based on erythrocyte and extracellular matrix content, which was assessed by means of computerized and observer analysis. Specimen weight, thrombus area, and cellular and monocyte content were measured.


RESULTS
Endogenous MCP-1 increased between days 1 and 7 in the thrombus (1-day median, 1.1 ng/g wet wt; 1-day range, 0.8 to 1.4 ng/g wet wt; 7-day median, 5.4 ng/g wet wt; 7-day range, 1.5 to 7.4 ng/g wet wt; P <.0001) and vein wall (1-day median, 1.5 ng/g wet wt; 1-day range, 0.8 to 4.3 ng/g wet wt; 7-day median, 3.3 ng/g wet wt; 7-day range, 2.7 to 8.3 ng/g wet wt; P <. 05). At 14 days, thrombus was incorporated in the vein wall, and total MCP-1 levels remained high (median, 3.9 ng/g wet wt; range, 1.1 to 7.4 ng/g wet wt). Less MCP-1 was found in the thrombus than the adjacent vessel wall at day 1 (P <.05), but there was no difference at day 7. MCP-1 could not be detected in the blood. MCP-1 injection into thrombus increased the computer (P =.016) and observer (P =.004) organization scores, reduced the thrombus area (from median, 3. 4 mm(2), and range, 1.5 to 5.7 mm(2), to median, 0.2 mm(2), and range, 0.02 to 2.6 mm(2); P =.048), and increased the surrounding vessel wall monocyte content (P =.008). Specimen weights of treated animals were lower than those of control animals (P <.02).


CONCLUSIONS
Venous thrombus MCP-1 levels increase during natural resolution. MCP-1 treatment increased the organization and resolution of thrombi. MCP-1 may therefore be of therapeutic use.
Humphries
J
J
Academic Department of Surgery, Guy's, King's, and St Thomas' Medical School, London, United Kingdom.
McGuinness
C L
CL
Smith
A
A
Waltham
M
M
Poston
R
R
Burnand
K G
KG
D000818:Animals; D018932:Chemokine CCL2 / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014680:Veins / Q000378:metabolism; D020246:Venous Thrombosis / Q000473:pathology* / Q000628:therapy*; D014945:Wound Healing / Q000502:physiology
D018932:Chemokine CCL2; D011994:Recombinant Proteins