Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution.
Human abdominal aortic aneurysm (AAA) expansion has been linked to the presence of a mural thrombus. Here we explored the mechanism of the continual luminal renewal of this thrombus and its ability to release biological markers potentially detectable in plasma. We also explored the ability of platelet inhibition to pacify the thrombus and to limit aneurysm progression in an experimental model. Blood samples and mural thrombi were collected in 20 AAA patients. In parallel, segments of sodium dodecyl sulfate-decellularized guinea pig aorta were xenografted onto the abdominal aorta of 30 rats to induce aneurysms. Fifteen rats received abciximab treatment and fifteen received irrelevant immunoglobulins. Procoagulant activity and platelet activation markers (microparticles, sP-selectin, sGPV, sCD40L) were increased threefold to fivefold in eluates from the luminal thrombus layer compared to other layers. All these markers were increased twofold to fivefold in patients' plasma compared to matched controls (P < 0.005). In the rat model, abciximab reduced both thrombus area and aneurysmal enlargement (P < 0.05). Platelet aggregation is probably responsible for the renewal of the thrombus in AAA. The luminal thrombus released markers of platelet activation that could easily be detected in plasma. Platelet inhibition limited aortic aneurysm expansion in a rat model, providing new therapeutic perspectives in the prevention of AAA enlargement.
Touat
Ziad
Z
INSERM U698, Cardiovascular Haematology, Bioengineering, and Remodeling, Centre Hospitalo-Universitaire, Bichat, Paris, France.
Ollivier
Veronique
V
Dai
Jianping
J
Huisse
Marie-Genevieve
MG
Bezeaud
Annie
A
Sebbag
Uriel
U
Palombi
Tony
T
Rossignol
Patrick
P
Meilhac
Olivier
O
Guillin
Marie-Claude
MC
Michel
Jean-Baptiste
JB
D000077284:Abciximab; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017544:Aortic Aneurysm, Abdominal / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000473:pathology; D023201:CD40 Ligand / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D006168:Guinea Pigs; D006331:Heart Diseases / Q000097:blood / Q000150:complications* / Q000473:pathology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D051381:Rats; D013927:Thrombosis / Q000097:blood / Q000150:complications* / Q000473:pathology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D023201:CD40 Ligand; D000077284:Abciximab