Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion.
OBJECTIVE
Early recognition of an acute coronary occlusion (ACO) improves clinical outcomes. Soluble fms-like tyrosine kinase-1 (sFLT1) is an endothelium-derived protein induced by hypoxia. We tested whether sFLT1 levels are elevated in ACO.


RESULTS
Serum sFLT1 levels were measured by enzyme-linked immunosorbent assay in patients with ST-segment elevations and angiographically confirmed ACO, unstable angina/non ST-segment elevation myocardial infarction, and 2 control groups. To further explore sFLT1 release, a mouse model of ACO and in vitro human coronary artery endothelial cell injury were used. sFLT1 levels were increased in ACO compared with unstable angina/non-ST-elevation myocardial infarction, catheterized controls, or healthy volunteers (200.7±15.5 versus 70.7±44.0 versus 10.2±4.0 versus 11.7±1.7 pg/mL respectively, P<0.001 versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (>15 pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of creatine kinase levels >10 ng/mL (P<0.01) and 85% had ultrasensitive troponin I levels >0.05 ng/mL (P<0.05). Within 60 minutes after symptom onset, sFLT1 was more sensitive than the MB isoform of creatine kinase or ultrasensitive troponin I for ACO (100% versus 20% versus 20% respectively; P≤0.01 for each). Within 60 minutes of ACO in mice, sFLT1 levels were elevated. Hypoxia and thrombin increased sFLT1 levels within 15 minutes in human coronary artery endothelial cells.


CONCLUSIONS
sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.
Molecular Cardiology Research Institute, Division of Cardiology, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. nkapur@tuftsmedicalcenter.org
Navin K
NK
Kapur
Kevin S
KS
Heffernan
Adil A
AA
Yunis
Tuan A
TA
Nguyen
Mark J
MJ
Aronovitz
Peter
P
Parpos
Szuhuei
S
Wilson
Corey K
CK
Baker
Michele L
ML
Esposito
Ameer
A
Shah
Carey D
CD
Kimmelstiel
Andrew
A
Weintraub
Richard H
RH
Karas
Michael E
ME
Mendelsohn
D000208:Acute Disease; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D054059:Coronary Occlusion / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*
C501162:FLT1 protein, human; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D003402:Creatine Kinase