Dr. Yang, Kai-Chien 's publons link picture


  • 2652-3597 (Lab) (Room No: N717)

  • Organ fibrosis and stromal biology
  • Cardiac regeneration
  • Non-coding RNA biology
  • Ion channel regulation and electrophysiology
  • Cardiac oxidative stress and arrhythmias

Education and Positions:
    • M.D. National Taiwan University
    • Ph.D. Washington University in St. Louis
    • Associate Professor, Department and Graduate Institute of Pharmacology, National Taiwan University
    • Attending physician, Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital

Highlight Detail

Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo

Dr. Yang, Kai-Chien
Science Advances, Jan 21, 2022




Although atherosclerosis preferentially develops at arterial curvatures and bifurcations where disturbed flow (DF) activates endothelium, therapies targeting flow-dependent mechanosensing pathways in the vasculature are unavailable. Here, we provided experimental evidence demonstrating a previously unidentified causal role of DF-induced endothelial TXNDC5 (thioredoxin domain containing 5) in atherosclerosis. TXNDC5 was increased in human and mouse atherosclerotic lesions and induced in endothelium subjected to DF. Endothelium-specific Txndc5 deletion markedly reduced atherosclerosis in ApoE-/- mice. Mechanistically, DF-induced TXNDC5 increases proteasome-mediated degradation of heat shock factor 1, leading to reduced heat shock protein 90 and accelerated eNOS (endothelial nitric oxide synthase) protein degradation. Moreover, nanoparticles formulated to deliver Txndc5-targeting CRISPR-Cas9 plasmids driven by an endothelium-specific promoter (CDH5) significantly increase eNOS protein and reduce atherosclerosis in ApoE-/- mice. These results delineate a new molecular paradigm that DF-induced endothelial TXNDC5 promotes atherosclerosis and establish a proof of concept of targeting endothelial mechanosensitive pathways in vivo against atherosclerosis.