Elevated tissue expression of thrombomodulatory factors correlates with acute symptomatic carotid plaque phenotype.
OBJECTIVE
Thrombomodulatory factors have been implicated in plaque instability. The aim was to examine the relationship between thrombomodulatory gene expression, timing of clinical events and plaque histology.


METHODS
Plaques were obtained from 40 consecutive patients undergoing carotid endarterectomy and divided into three groups (group 1, early symptomatic, within 1 month; group 2, late symptomatic, 1-6 months and group 3, asymptomatic). Total RNA was isolated to determine the expression of tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), plasminogen activator inhibitor-1 (PAI-1), tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), CD68 and vascular endothelial-cadherin (VE-Cadherin).


RESULTS
Expression of t-PA, PAI-1, TF, TFPI, TM, CD68 and VE-cadherin were significantly increased in the early symptomatic group (p=0.019, 0.028, 0.018, 0.025, 0.038, 0.016 and 0.027 respectively), but the level of gene expression in the late symptomatic group was indistinguishable from the asymptomatic group. The incidence of plaque rupture and intraplaque haemorrhage was significantly increased in the early symptomatic groups (58% versus 18%/18% group 2/3, and 55% versus 6%/9% respectively, p<0.05 for both).


CONCLUSIONS
Expression of thrombomodulatory genes is increased in unstable plaques, though levels after 1 month are comparable to asymptomatic plaques. This transient rise may influence plaque instability, and rapid resolution mirrors the clinical reduction in risk of further thrombo-embolic events.
St George's Vascular Institute, St Georges Healthcare NHS Trust, London, UK.
S
S
Sayed
G W
GW
Cockerill
E
E
Torsney
R
R
Poston
M M
MM
Thompson
I M
IM
Loftus
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics*; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000235:genetics*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002339:Carotid Arteries / Q000378:metabolism* / Q000601:surgery; D002341:Carotid Artery Thrombosis / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D004247:DNA / Q000235:genetics*; D016894:Endarterectomy, Carotid; D004730:Endothelium, Vascular / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018180:Thrombomodulin / Q000096:biosynthesis / Q000235:genetics; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics; D000099152:Cadherin 5; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001779:Blood Coagulation Factors; D015820:Cadherins; D004247:DNA; D065427:Factor Xa Inhibitors; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D000099152:Cadherin 5; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C051928:lipoprotein-associated coagulation inhibitor