Cathepsin L promotes vascular intimal hyperplasia after arterial injury

Jingjing Cai, Hua Zhong, Jinze Wu, Rui Fang Chen, Huan Yang, Yousef Al-Abed, Ying Li, Xiaohui Li, Weihong Jiang, Marcelo F. Montenegro, Hong Yuan, Timothy R. Billiar*, Alex F. Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


The inflammatory pathways that drive the development of intimal hyperplasia (IH) following arterial injury are not fully understood. We hypothesized that the lysosomal cysteine protease cathepsin L activates processes leading to IH after arterial injury. Using a mouse model of wire-induced carotid artery injury, we showed that cathepsin L activity peaks at d 7 and remains elevated for 28 d. Genetic deletion of cathepsin L prevented IH and monocyte recruitment in the carotid wall. The injury-induced increases in cathepsin L mRNA and activity were mitigated in mice with myeloid-specific deletion of toll-like receptor 4 (TLR4) or myeloid differentiation primary response gene 88 (MyD88). We further discovered that the HIV protease inhibitor saquinavir (SQV), which is known to block recombinant mouse cathepsin L activity in vitro, prevented IH after arterial injury. SQV also suppressed LPS (TLR4 agonist)-induced monocyte adhesion to endothelial monolayers. These findings establish cathepsin L as a critical regulator of the inflammation that leads to IH and that the TLR4-MyD88 pathway in myeloid lineages regulates cathepsin L expression in the vessel wall following wire injury. The Food and Drug Administration-approved drug SQV blocks IH though mechanisms that may include the suppression of cathepsin L.

Original languageEnglish
Pages (from-to)92-100
Number of pages9
JournalMolecular medicine (Cambridge, Mass.)
StatePublished - 2017
Externally publishedYes


  • Al-Abed
  • Arterial injury
  • Arterial occlusive disease
  • Billiar
  • Cai
  • Cathepsin L
  • Cathepsins
  • Chen
  • IH
  • Inflammation
  • Intimal hyperplasia
  • Jiang
  • Li
  • Lysosomal cysteine protease
  • Montenegro
  • SQV
  • Saquinavir
  • Wu
  • Yang
  • Yuan
  • Zhong


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