Research Paper Volume 12, Issue 17 pp 16775—16802

Figure 3. Mechanism or interactive pathway of TFPI, ADAMTS7 and APOE in lipid metabolism homeostasis in longevity. TFPI rs7586970 TT, with normal function, can be formed lipoprotein-associated coagulation inhibitor (LACI) through C-terminal region glycophosphatidylinositol (GPI) anchoring point by binding to LDL receptor (LDLR)-related proteins, known as Low-Density Lipoprotein Receptor Associated Protein 1(LRP1). APOE also regulates blood cholesterol levels by binding to LDLR. When the blood lipid concentration increases, APOE transport of lipids by binding to LRP1. Then, TFPI rs7586970 TT interacts with APOE via the LRP1to carry out endocytosis. After that convert lipid to cholesterol ester (CE). The CE is broken down into VLDL by enzymolysis in lysosomes. In the meantime, ADAMTS7 rs3825807 AA activates PDGFR-β enzyme activity to bond PDGF. The combination of PDGF and PDGFR-β can result in VSMC migration in the MAPK pathway. PDGFR-β is a typical tyrosine receptor kinase that activates downstream growth factors, such as receptor-binding protein 2 (Grb2), son of sevenless (Sos), Ras and other factors, activating the MAPK pathway and stimulating hemichannel opening to release VLDL into the extracellular environment or adjacent cells.