Genetic or therapeutic neutralization of ALK1 reduces LDL transcytosis and atherosclerosis in mice.

ABSTRACT: Low-density lipoprotein (LDL) accumulation in the arterial wall contributes to atherosclerosis initiation and progression¹. Activin A receptor-like type 1 (ACVRL1, called activin-like kinase receptor (ALK1)) is a recently identified receptor that mediates LDL entry and transcytosis in endothelial cells (ECs)^2,3. However, the role of this pathway in vivo is not yet known. In the present study, we show that genetic deletion of ALK1 in arterial ECs of mice substantially limits LDL accumulation, macrophage infiltration and atherosclerosis without affecting cholesterol or triglyceride levels. Moreover, a selective monoclonal antibody binding ALK1 efficiently blocked LDL transcytosis, but not bone morphogenetic protein-9 (BMP9) signaling, dramatically reducing plaque format

SUBMITTER: Lee S 

PROVIDER: S-EPMC11358031 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature