FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice.

ABSTRACT: Objective- Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member of several coronary artery disease-associated pathways. Thus, our objective is to determine the role of FURIN in atherosclerosis. Approach and Results- In vitro, FURIN inhibitor treatment resulted in reduced monocyte migration and reduced macrophage and vascular endothelial cell inflammatory and cytokine gene expression. In vivo, administration of an irreversible inhibitor of FURIN, α-1-PDX (α1-antitrypsin Portland), to hyperlipidemic Ldlr^-/-<

SUBMITTER: Yakala GK 

PROVIDER: S-EPMC6393193 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature