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 (200.7Ϯ15.5 versus 70.7Ϯ44.0 versus 10.2Ϯ4.0 versus 11.7Ϯ1.7 pg/mL respectively, PϽ0.001 versus ACO). At presentation, all ACO patients had elevated sFLT1 levels (Ͼ15 pg/mL, 99th percentile in controls), whereas 57% had levels of the MB isoform of creatine kinase levels Ͼ10 ng/mL (PϽ0.01) and 85% had ultrasensitive troponin I levels Ͼ0.05 ng/mL (PϽ0.05). 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; PՅ0.01 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. Key Words: acute coronary syndromes Ⅲ coronary artery disease Ⅲ coronary heart disease Ⅲ endothelium Ⅲ thrombosis A cute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. During acute coronary occlusion (ACO), a delay in diagnosis beyond 2 hours after symptom onset reduces the benefits of reperfusion therapy by Ϸ50%. 1-3 In most cases, ACO is clinically diagnosed based on electrocardiographic (ECG) evidence of ST-segment elevation (STE) and symptoms consistent with myocardial ischemia. However, STE alone is not specific to coronary occlusion. Conversely, patients with ACO may have no evidence of STE. 4 The difficulty of timely identification of ACO is increased further because currently used biomarkers for the diagnosis of AMI, 5 such as the MB isoform of creatine (CK) kinase (CK-MB), myoglobin, and standard or ultrasensitive troponin require cardiomyocyte damage and may not be specific to coronary occlusion. 6,7 Therefore, relying on the ECG or biomarkers of myocyte necrosis to distinguish ACO from noncardiac causes of chest pain may be accompanied by both false-positive and negative results.Human vascular endothelial growth factor receptor-1, also known as fms-like tyrosine kinase-1 (FLT1), was originally identified in human placental tissue and later characterized as a receptor for the angiogenic factors vascular endothelial growth factor-A, vascular endothelial growth factor-B, and placental growth factor. 8 FLT1 is highly expressed by endothelial cells, vascular smooth muscle cells, and monocytes. 9,10 A trunca...