Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Atherosclerosis, or hardening of the arteries, occurs when fat, cholesterol, and other substances build up and form plaques inside the arteries. These plaques can narrow the arteries and make them stiffer and cause severe health problems. Now findings of a new study from Yale University School of Medicine could lead to a new strategy to prevent the accumulation of LDL cholesterol in the vessel wall. The study, published in the journal Nature Communications, reveals that a protein called activin-like kinase 1 (ALK1) mediates LDL uptake into endothelial cells. CusAb provides you with FITC conjugated antibody and other biomolecules like ALK1. It is well known that the LDL receptor (LDLR) helps transport LDL. However, some people lacking LDLR still have high levels of LDL. Why this phenomenon occurs is not clear. In this study, Yale researchers wanted to identify new pathways of LDL transport. By performing a genome-wide RNAi screen in endothelial cells, they identified that a protein known as ALK1 facilitated the transport of LDL into endothelial cells. Endothelial cells?are flat epithelial?cells?that form the?endothelium?which lines?blood vessels?and some other tissues. LDL in the blood has to enter the endothelium and cross it to reach the subendothelial area, where it is retained and accumulates over time. A total of more than 18,000 genes from the endothelium were screened in the study. Finally, the researchers discovered that the ALK1 protein can attach to LDL and then promote LDL uptake from blood into tissue. These data suggested that ALK1 plays a role in LDL accumulation. According to lead researcher William C. Sessa, antibodies and small molecules that inhibit ALK1 might help reduce LDL accumulation and thus prevent atherosclerosis, the leading cause of heart attacks. Furthermore, the team identified a set of genes such as ARHGAP9, SDC1, SLC38A3 and ATP6V1C1, that were implicated in atherosclerosis development, in regulating cellular cholesterol levels or in LDL uptake. Collectively, the research reveals new pathways for LDL uptake into endothelial cells and offers ways to reduce LDL uptake in blood vessels.
