# Phage Display Preparation of Specific Polypeptides in Atherosclerotic Foam Cells
## 1 Introduction  
Atherosclerotic lesion (atheroma) is a progressive chronic inflammatory disease characterized by a gradual asymmetric focal thickening of the intima of an artery, and hardening of the artery that ultimately leads to a reduction in lumen diameter and potentially results in ischemia following plaque rupture [1]; atherosclerotic complications are the most common causes of death in modern societies. Atherosclerosis is an inflammatory disease with high plasma concentrations of cholesterol, particularly those of low-density lipoprotein (LDL) cholesterol, which is one of the principal risk factors for atherosclerosis [2]. Previous studies have clarified that the process of atherogenesis consists of much more than the accumulation of lipids within the artery wall; atherogenesis involves cells, connective-tissue elements, lipids, and debris [3]. Blood-borne inflammatory and immune cells constitute an essential part of atheroma, with the remainder including vascular endothelial and smooth muscle cells. Atheroma is preceded by a fatty streak, the earliest type of lesion, which is an accumulation of lipid-laden cells beneath the endothelium. Most of these cells in the fatty streak are macrophages, together with some T cells. Fatty streaks are prevalent in infants and young people, never cause symptoms, and may progress to atheroma or eventually disappear [4]. In the center of an atheroma, foam cells and extracellular lipid droplets form a core region surrounded by a cap of smooth muscle cells and a collagen-rich matrix.  
T cells, macrophages, and mast cells infiltrate the lesion and are particularly abundant in the shoulder region where the atheroma grows [5].  
The formation of macrophage foam cells in the intima of arteries is a major hallmark of early-stage atherosclerotic lesions. Uncontrolled uptake of oxidized low-density lipoprotein (ox-LDL), excessive cholesterol esterification, or impaired cholesterol release result in accumulation of cholesterol ester stored as cytoplasmic lipid droplets and subsequently trigger the formation of foam cells [6]. Scavenger receptors (SRs), such as CD36 and SR class A (SR-A), are the principal receptors responsible for the binding and uptake of ox-LDL in macrophages. ATP-binding cassette (ABC) transporter A1(ABCA1), ABCG1, and scavenger receptor BI (SR-BI) mediate cholesterol export from macrophages. Acyl coenzyme A, cholesterol acyltransferase 1 (ACAT1), and neutral cholesteryl ester hydrolase (nCEH) play critical roles in cholesterol esterification [7; 8; 9]. The two main contributing factors of the acellular lipid core of advanced atherosclerosis are the accumulation of extracellular lipid and the death of macrophage foam cells. In addition, advanced atherosclerotic lesions develop from smaller lesions, fatty dots, and streaks composed almost entirely of macrophage foam cells [10; 11; 12; 13]. From early fatty streak lesions to advanced plaques, macrophage-derived foam cells are integral to the development and progression of atherosclerosis. Thus, early diagnosis of foam cells plays a vital role in atherosclerosis intervention, and therefore, as a starting point, in this study, we aimed to isolate and prepare foam cell-specific polypeptides using a phage display platform, the QD-based fluorescence image also revealed the binding of these prepared polypeptides with foam cells (Figure 1). The polypeptides we obtained in this study could lay the foundation for developing a rapid detection kit for early atherosclerosis lesions and could provide new materials for research on the mechanisms of foam cell formation and the development of blocking drugs.