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Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque
Diana Bonderman1, Alexander Teml, Johannes Jakowitsch
1Department of Cardiology, University of Vienna, Austria.
Insights
Tissue factor (TF) released from atherosclerotic plaque causes no-reflow (NR) in coronary arteries. This study demonstrates TF
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pathophysiology
Background:
- No-reflow (NR) is an acute reduction in coronary blood flow without vessel obstruction.
- Tissue factor (TF) is present in atherosclerotic plaques and may contribute to NR.
Purpose of the Study:
- To investigate the role of TF in causing acute coronary NR.
- To determine if TF released from plaque is a cause of NR.
Main Methods:
- Measured TF activity in carotid artery plaque and particulate material from coronary blood.
- Assessed TF antigen levels in coronary blood during NR and after flow restoration in patients.
- Administered atherosclerotic material and purified TF into porcine coronary arteries to assess NR induction.
Main Results:
- TF activity was detected in atherosclerotic plaque and coronary particulate matter.
- TF antigen levels were significantly higher during NR compared to post-flow restoration.
- Intracoronary TF administration induced NR in a porcine model.
Conclusions:
- Active TF is released from dissected coronary atherosclerotic plaque.
- Blood-borne TF in the coronary circulation is a significant factor causing NR.
- TF plays a causal role in the no-reflow phenomenon.
Abstract:
Defined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.03 +/- 13.00 pg/cm(2) luminal plaque surface). Active TF was sedimented, indicating that TF was associated with membranes. Coronary blood was drawn from 6 patients undergoing coronary interventions with the distal protection device PercuSurge GuardWire (Traatek, Miami, FL). Fine particulate material that was recovered from coronary blood showed TF activity (corresponding to 91.1 +/- 62.16 pg/mL authentic TF). To examine the role of TF in acute coronary NR, blood was drawn via a catheter from coronary vessels in 13 patients during NR and after restoration of flow. Mean TF antigen levels were elevated during NR (194.3 +/- 142.8 pg/mL) as compared with levels after flow restoration (73.27 +/- 31.90 pg/mL; P =.02). To dissect the effects of particulate material and purified TF on flow, selective intracoronary injection of atherosclerotic material or purified relipidated TF was performed in a porcine model. TF induced NR in the model, thus strengthening the concept that TF is causal, not just a bystander to atherosclerotic plaque material. The data suggest that active TF is released from dissected coronary atherosclerotic plaque and is one of the factors causing the NR phenomenon. Thus, blood-borne TF in the coronary circulation is a major determinant of flow.