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Impaired fibrinolysis in coronary artery disease
R B Francis1, D Kawanishi, T Baruch
1Division of Hematology, University of Southern California School of Medicine, Los Angeles.
Insights
Impaired fibrinolysis, characterized by increased plasminogen activator inhibitor (PAI) activity and reduced tissue-type plasminogen activator (t-PA) release, is associated with coronary artery disease (CAD). This suggests a link between blood clot breakdown and heart disease risk.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Biochemistry
Background:
- Coronary artery disease (CAD) is a leading cause of mortality worldwide.
- Fibrinolysis, the breakdown of blood clots, plays a crucial role in cardiovascular health.
- Endothelial dysfunction is implicated in the pathogenesis of CAD.
Purpose of the Study:
- To investigate endogenous fibrinolytic function in patients with CAD.
- To assess the role of tissue-type plasminogen activator (t-PA) and its inhibitor (PAI) in CAD.
- To explore potential differences in fibrinolysis between CAD patients and healthy controls.
Main Methods:
- Assessed plasma levels of t-PA antigen, t-PA activity, PAI activity, plasminogen, and alpha-2 plasmin inhibitor (alpha-2 PI) in 99 CAD patients and 28 controls.
- Measured endothelial release of t-PA via venous occlusion testing.
- Analyzed correlations between fibrinolytic parameters and plasma fibrinogen levels.
Main Results:
- CAD patients exhibited significantly higher PAI activity and lower t-PA activity post-venous occlusion compared to controls.
- Younger CAD patients (<45 years) showed significantly reduced t-PA antigen release.
- Elevated plasma fibrinogen levels were observed in CAD patients, correlating positively with PAI activity.
Conclusions:
- Impaired fibrinolysis, involving increased PAI activity and reduced endothelial t-PA release, is associated with CAD.
- These findings suggest a contribution of dysregulated fibrinolysis to the development of coronary artery disease.
- Targeting fibrinolytic pathways may offer therapeutic potential for CAD management.
Abstract:
We assessed endogenous endothelial-dependent fibrinolysis in 99 subjects with coronary artery disease (CAD) documented by angiography and in 28 control subjects with normal coronary arteries on angiography. We used specific, sensitive assays for plasma tissue-type plasminogen activator (t-PA) antigen, t-PA activity, plasminogen activator inhibitor (PAI) activity, plasminogen, and alpha-2 plasmin inhibitor (alpha-2 PI). Mean PAI activity was significantly higher, and mean t-PA activity after venous occlusion of the upper arm (a standard test of the capacity of vascular endothelium to release t-PA) was significantly lower in subjects with CAD than in subjects with normal coronary arteries. The mean increment in t-PA antigen after venous occlusion was significantly lower than normal in subjects with CAD with onset of symptoms before age 45 years. Subjects with CAD had a significantly increased mean plasma fibrinogen level compared with control subjects, and a significant positive correlation was observed between PAI activity and plasma fibrinogen in subjects with CAD. No significant abnormalities of plasminogen or alpha-2 PI were observed in any subset of subjects with CAD. These data support an association between impaired fibrinolysis and CAD, with contributions from both increased PAI activity and in younger subjects from reduced endothelial t-PA release.