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Cathepsin L Promotes Vascular Intimal Hyperplasia after Arterial Injury.
- Source :
-
Molecular Medicine . 2017, Vol. 23, p92-100. 9p. 1 Diagram, 3 Graphs. - Publication Year :
- 2017
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10761551
- Volume :
- 23
- Database :
- Academic Search Index
- Journal :
- Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 135381054
- Full Text :
- https://doi.org/10.2119/molmed.2016.00222