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

Xue Xiao, Lin Xu, Junhui Zhang, Xiaoyue Hu, Evanthia Pashos, George Tellides, Philip W. Shaul, Warren L. Lee, Carlos Fernandez-Hernando, Anne Eichmann, William C. Sessa, Sungwoon Lee, Hubertus Schleer, Hyojin Park, Erika Jang, Michael Boyer, Bo Tao, Ana María Gámez Méndez, Abhishek Singh, Ewa Folta-StogniewXinbo Zhang, Lingfeng Qin

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4 Citas (Scopus)


Low-density lipoprotein (LDL) accumulation in the arterial wall contributes to atherosclerosis initiation and progression 1 . 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 formation in LDL receptor knockout mice fed a high-fat diet. Thus, our results demonstrate that blocking LDL transcytosis into the endothelium may be a promising therapeutic strategy that targets the initiating event of atherosclerotic cardiovascular disease.
Idioma originalEnglish
Páginas (desde-hasta)438-448
Número de páginas11
PublicaciónNature cardiovascular research
EstadoPublished - may 2023
Publicado de forma externa

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© 2023, The Author(s).


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