Related Experiment Videos
[Coagulation/fibrinolytic system and platelet in acute coronary syndrome]
1Department of Molecular and Laboratory Medicine, Kagoshima University School of Medicine.
Insights
The coagulation/fibrinolytic system and platelets are key in acute coronary syndrome (ACS) and atherosclerosis. Oxidized LDL and AGEs impair blood vessel antithrombotic function, contributing to ACS.
Area of Science:
- Cardiovascular Medicine
- Hematology
Background:
- Coronary atherosclerosis is a primary condition underlying acute coronary syndrome (ACS).
- Hypercholesterolemia and diabetes mellitus (DM) are significant risk factors for coronary atherosclerosis and ACS.
- The coagulation/fibrinolytic system and platelet function are implicated in both atherosclerosis and ACS pathogenesis.
Purpose of the Study:
- To review the roles of the coagulation/fibrinolytic system and platelets in coronary atherosclerosis and ACS.
- To elucidate the mechanisms by which risk factors like oxidized LDL and advanced glycation end products (AGEs) contribute to ACS.
Main Methods:
- Literature review focusing on the involvement of hemostatic factors in coronary atherosclerosis and ACS.
- Analysis of cellular and molecular pathways affected by hypercholesterolemia and diabetes.
Main Results:
- Oxidized LDL and AGEs activate endothelial cells, down-regulating thrombomodulin and tissue plasminogen activator (t-PA) expression.
- Oxidized LDL and AGEs up-regulate tissue factor and PAI-1 (t-PA inhibitor), impairing endothelial antithrombotic function and promoting ACS.
- High shear stress in atherosclerotic lesions may induce shear stress-induced platelet aggregation (SIPA), contributing to ACS pathogenesis.
Conclusions:
- Impaired endothelial antithrombotic function due to oxidized LDL and AGEs is a key mechanism in coronary atherosclerosis and ACS.
- Shear stress-induced platelet aggregation may play a significant role in the development of ACS.
Abstract:
Coagulation/fibrinolytic system and platelet function play roles not only in the onset of acute coronary syndrome (ACS) but also in the development of atherosclerosis, which is a major underlying condition of ACS. In this paper we reviewed the involvement of coagulation/fibrinolytic system and platelet in coronary atherosclerosis and ACS. It is well known that hyperchoresterolemia and diabetes mellitus (DM) are the important risk factor for coronary atherosclerosis and ACS. Both oxidized LDL and advanced glycation endproduct (AGE) activate endothelial cells with down-regulating thrombomodulin and tissue plasminogen activator(t-PA) expression. Moreover the oxidized LDL and AGE up-regulate the expression of tissue factor, and t-PA inhibitor, PAI-1. Thus Ox-LDL and AGE impair the endothelial antithrombotic function and result ACS. These may explain the pathomechanism of coronary sclerosis and ACS. In the atherosclerotic lesion with narrowing the lumen, high shear stress may be occurred. Recent observations suggested that high shear stress induces platelets aggregation named as shear stress induced platelet aggregation (SIPA), which may also have very important role for the pathogenesis in ACS.