Hepatocyte-Specific Knockout of YAP Protects Against Atherosclerosis via Inhibition of ANGPTL3 in Mice.

Arterioscler Thromb Vasc Biol 2026

Hou Y, Zhang X, Sun X, Qin Q, Jia M et al.

Abstract

BACKGROUND: Lipid-lowering therapy is a cornerstone in the treatment of atherosclerotic cardiovascular diseases. Although some lipid-lowering drugs have demonstrated positive effects in patients with atherosclerotic cardiovascular diseases, their effects are limited in those with homozygous familial hypercholesterolemia. It is essential to seek new lipid-lowering targets. YAP (Yes-associated protein) may be involved in lipid metabolism in the liver; therefore, we investigated the function of hepatocyte YAP in hyperlipidemia and atherosclerosis. METHODS: Hyperlipidemia models were generated in apoE knockout (apoE RESULTS: High-cholesterol diet-fed apoE CONCLUSIONS: Taken together, our findings revealed a novel role for the YAP-TEAD4-ANGPTL3 axis in lipid metabolism independent of LDLR. Inhibition of hepatocyte YAP may be an effective lipid-lowering strategy for homozygous familial hypercholesterolemia.

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