Effects Of CD40-CD40 Ligand Interaction On Human Umbilical Vein Endothelial Cells Expression Of Tissue Factor, Matrix Metalloproteinases And Their Inhibitors

[Background] Acute coronary syndrome (ACS), including unstable angina, acute myocardial infarction and ischemic sudden death, are one of the main public health problems and the leading cause of death in the industrialized world. It is of paramount significance to explore the underlying pathophysiological mechanism for the prevention and treatment of ACS. Acute coronary thrombus formation secondary to vulnerable atherosclerotic plaque is the main pathological basis of ACS. By overexpressing tissue factor (TF) and matrix metalloproteinases (MMPs), the endothelial cells overlying vulnerable atherosclerotic plaque participate actively in fibrous cap destruction, new blood vessel formation, endothelial cells desquamation, and superficial thrombus elicitation, the processes that have great relevance to plaque stability. The signals that induce these changes remain obscure. Recent studies have localized CD40 ligand (CD40L), an immunoregulatory signaling molecule, and its receptor CD40 in human atherosclerotic lesions, especially on macrophages and endothelial cells in vulnerable plaque. The amount and distribution pattern of CD40 and CD40L parallel endothelial cells expression of TF and MMPs, which suggests that CD40-CD40L interaction may be the key pathway in inducing endothelial dysfunction favoring ACS.[Objective] The effects of CD40-CD40L interaction on human umbilical vein...