Researchers have discovered a protein called ALK1 that plays a role in the buildup of low-density lipoprotein (LDL) cholesterol in blood vessels.
They mentioned in a news release that the results could help block LDL and prevent or slow the clogging of arteries that lead to heart disease.
Lead researcher Jan R. Kraehling, PhD, of Yale University’s School of Medicine in New Haven, Connecticut, and colleagues published their findings online Nov. 21 in Nature Communications.
“Detailed analysis shows that ALK1 fits the criteria for an endothelial cell specific, LDL-binding protein sufficient to promote LDL uptake and transcytosis,” the researchers wrote. “This is supported by knockdown or overexpression studies showing that ALK1 mediates LDL uptake and transcytosis in an LDL [receptor] and sterol sensing independent manner by the direct binding of LDL to the ectodomain of ALK1.”
The researchers used a genome-wide RNAi approach and evaluated 18,119 genes. Two other genes, called ANGPT4 and GPR182, fulfilled the researchers’ criteria for the follow-up screen. However, they noted that ANGPT4 was not well characterized as a ligand and GPR182 was an orphan receptor. Thus, they focused on ALK1, which they noted was a TGF-β-type 1 receptor that binds bone morphogenetic proteins−9 and −10 ligands with high affinity.
“The discovery of ALK1 as an LDL-binding protein implies that it might initiate the early phases of atherosclerosis," William C. Sessa, PhD, the study’s senior author, said in a news release. “If we can find a way of blocking ALK1 using small molecules or antibodies, it might be used in combination with lipid-lowering strategies.”
Executive Editor
Tim Casey joined TriMed Media Group in 2015 as Executive Editor. For the previous four years, he worked as an editor and writer for HMP Communications, primarily focused on covering managed care issues and reporting from medical and health care conferences. He was also a staff reporter at the Sacramento Bee for more than four years covering professional, college and high school sports. He earned his undergraduate degree in psychology from the University of Notre Dame and his MBA degree from Georgetown University.