Human coronary thrombus formation is associated with degree of plaque disruption and expression of tissue factor and hexokinase II.
BACKGROUND
Atherosclerotic plaque thrombogenicity is a critical factor that affects thrombus formation and the onset of acute myocardial infarction (AMI). The aim of this study was to identify the vascular factors involved in thrombus formation and AMI onset.


RESULTS
Culprit lesions in 40 coronary arteries with thrombi at autopsy after lethal AMI and non-cardiac death (asymptomatic plaque disruption) were analyzed on histology. Thrombus size, ratio of thrombus to lumen area, length of plaque disruption, and immunopositive areas for tissue factor (TF) and hexokinase (HK)-II were significantly larger in coronary arteries with AMI than with asymptomatic plaque disruption. The size of coronary thrombus positively correlated with the length of plaque disruption (r=0.80) and with immunopositive areas for TF (r=0.38) and HK-II (r=0.40). Because both M1 and M2 macrophages express TF and HK-II in symptomatic plaques, we assessed TF and HK-II expression in M1- and M2-polarized macrophages. The expression of TF was increased and that of HK-II was decreased in M2-, compared with M1-polarized THP-1 macrophages. Inhibiting glycolysis enhanced TF expression in the macrophages partly via hypoxia inducible factor-1α.


CONCLUSIONS
The degree of plaque disruption and expression of TF and HK-II appear to be important vascular factors for AMI onset, and polarized macrophages make a distinct contribution to thrombogenicity and glucose metabolism.
Department of Pathology, Miyazaki University Hospital, University of Miyazaki.
Nozomi
N
Okuyama
Shuntaro
S
Matsuda
Atsushi
A
Yamashita
Sayaka
S
Moriguchi-Goto
Naoki
N
Sameshima
Takashi
T
Iwakiri
Yunosuke
Y
Matsuura
Yuichiro
Y
Sato
Yujiro
Y
Asada
D001344:Autopsy; D016022:Case-Control Studies; D002423:Cause of Death; D002460:Cell Line; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D003328:Coronary Thrombosis / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D003331:Coronary Vessels / Q000201:enzymology* / Q000473:pathology*; D005786:Gene Expression Regulation; D006019:Glycolysis; D006593:Hexokinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology; D009203:Myocardial Infarction / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013925:Thromboplastin; C000609700:HK2 protein, human; D006593:Hexokinase