In the maintenance of the vascular system and homeostasis, the endothelial cells, the collagen in the subendothelial tissue, and the tissue factor (TF) are important. In particular, the endothelial cells form tunica intima and have three thromboregulators inhibiting thrombus formation: nitric oxide, prostacyclin, and ectonucleotidase CD39 [2].

Atherosclerosis is a chronic inflammatory disease developed by innate and adaptive immunity with the lipids in the artery wall as major components (Fig. 1.4). At first, it is accompanied by dysfunction in the vascular endothelial cells, and as the blood vessels are exposed to excessive lipids (low-density lipoprotein, LDL), the lipids start to accumulate under the intima. If a person is frequently exposed to different risk factors (hypertension, diabetes, smoking, infection, stress, etc.), the damage in endothelial cells becomes severe, and due to the damaged endothelial cells, more LDL cholesterol particles accumulate in the extracellular matrix (ECM), which becomes the place where the damage caused by the oxidation and decomposition enzymes most frequently occurs. The modified LDL activates various inflammatory responses, and its major mechanism is the infiltration of monocytes, which plays the most important role in innate immunity. Also, it is known that adaptive immunity, including the helper T cells (Th1 and Th2) and the antibodies, plays a significant role in the expansion of arteriosclerosis. If monocytes infiltrate and reach the subendothelial region, they are differentiated into macrophage by the macrophage colony-stimulating factor. Macrophage can be differentiated into subtypes with various types and functions according to the environment around it, and such a process is called “polarization.” There are two macrophage subtypes that can be very clearly distinguished from each other depending on the atherosclerosis process, which are known as M1 and M2 (Fig. 1.5). A differentiated macrophage goes through a lipid-containing macrophage while expressing a surface pattern recognition receptor well receiving the modified LDL and changes to a foam cell. As the foam cell secretes cytokines and growth factors, lesions progress, and the vascular smooth muscle cell (VSMC) moves from the media to the intima, where ECM materials, which are important in fibrous cap formation, are produced. In fact, many lipid-containing macrophages are removed by M2 macrophage through the process called “efferocytosis” after initially going through the process of apoptosis. Nevertheless, as macrophage excessively takes apoptosis cells, the endoplasmic reticulum is stressed. Consequently, defects in efferocytosis occur, which isolates the death of the macrophage and lipids, the inflammatory factor, the coagulation factor such as TF, and the matrix metalloproteinases (MMPs). MMP induces the rupture of the atherosclerotic plaque while decomposing the ECM scaffold such as the fibrous cap. The plaque vulnerability is exacerbated as the infiltration of VSMC becomes smaller, and more immature and leaky microvessels occur in the core necrotic plaque.