Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion

Navin K. Kapur, Kevin S. Heffernan, Adil A. Yunis, Tuan A. Nguyen, Mark J. Aronovitz, Peter Parpos, Szuhuei Wilson, Corey K. Baker, Michele L. Esposito, Ameer Shah, Carey D. Kimmelstiel, Andrew Weintraub, Richard H. Karas, Michael E. Mendelsohn

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Keywords

  • acute coronary syndromes
  • coronary artery disease
  • coronary heart disease
  • endothelium
  • thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Kapur, N. K., Heffernan, K. S., Yunis, A. A., Nguyen, T. A., Aronovitz, M. J., Parpos, P., Wilson, S., Baker, C. K., Esposito, M. L., Shah, A., Kimmelstiel, C. D., Weintraub, A., Karas, R. H., & Mendelsohn, M. E. (2011). Elevated soluble fms-like tyrosine kinase-1 levels in acute coronary occlusion. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(2), 443-450. https://doi.org/10.1161/ATVBAHA.110.215897