This paper presents a mathematical characterization of the main features of the molecular communication between platelets and endothelial cells via CD40 signaling during the initial phases of atherosclerosis, known also as atherogenesis. We demonstrate through laboratory experimentation that the release of soluble CD40L molecules from platelets in a fluid medium is enough to trigger expression of adhesion molecules on endothelial cell's surface; that is, physical contact between the platelets and the endothelial cells is not necessary. We also propose the mathematical model of this communication, and we quantify the model parameters by matching the experiment results to the model. In addition, this mathematical model of platelet-endothelium interaction, along with propagation models typical of blood vessels, is incorporated into a simulation platform. Analysis of the simulation results indicates that these enhancements render the simulator a useful tool upon which to base discussion for planning research, and has the potential to be an important step in the understanding, diagnosis, and treatment of cardiovascular diseases.