TY - JOUR
T1 - Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion
AU - Kapur, Navin K.
AU - Heffernan, Kevin S.
AU - Yunis, Adil A.
AU - Nguyen, Tuan A.
AU - Aronovitz, Mark J.
AU - Parpos, Peter
AU - Wilson, Szuhuei
AU - Baker, Corey K.
AU - Esposito, Michele L.
AU - Shah, Ameer
AU - Kimmelstiel, Carey D.
AU - Weintraub, Andrew
AU - Karas, Richard H.
AU - Mendelsohn, Michael E.
PY - 2011/2
Y1 - 2011/2
N2 - 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. Methods and 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. Conclusion-: sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.
AB - 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. Methods and 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. Conclusion-: sFLT1 levels may be an early indicator of endothelial hypoxia in ACO.
KW - acute coronary syndromes
KW - coronary artery disease
KW - coronary heart disease
KW - endothelium
KW - thrombosis
UR - http://www.scopus.com/inward/record.url?scp=79551493677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551493677&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.110.215897
DO - 10.1161/ATVBAHA.110.215897
M3 - Article
C2 - 21071694
AN - SCOPUS:79551493677
SN - 1079-5642
VL - 31
SP - 443
EP - 450
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 2
ER -