Characterizing cathepsin activity and macrophage subtypes in excised human carotid plaques

Ihab Abd-Elrahman, Karen Meir, Hisanori Kosuge, Yael Ben-Nun, Tommy Weiss Sadan, Chen Rubinstein, Yaacov Samet, Michael V. McConnell, Galia Blum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Background and Purpose-Atherosclerosis is a leading cause of mortality worldwide, contributing to both strokes and heart attacks. Macrophages are key players in atherogenesis, promoting vascular inflammation and arterial remodeling through cysteine cathepsin proteases. We used a cathepsin-targeted activity-based probe in human carotid plaque to assess its diagnostic potential and evaluate macrophage subtypes ex vivo. Methods-Carotid plaque specimens surgically removed during endarterectomy from 62 patients (age range, 38% female, 28% symptomatic) were graded pathologically as either stable (Grade 1) or unstable (Grade 2 or 3). A cathepsin activitybased probe was used to quantify individual cathepsins in plaque tissue and macrophage subtypes. Results-Cathepsin B and S activities were increased in unstable carotid plaques. They were quantified using the probe to biochemically investigate individual cathepsins (Cathepsin B and S: 0.97 and 0.90 for grade 3 versus 0.51 and 0.59 for grade 1; P=0.006 and P=0.03 arbitrary units (AU), respectively). Higher cathepsin activity was observed in carotid plaques from symptomatic patients (Cathepsin B and S: 0.65 and 0.77 for asymptomatic, 0.99 and 1.17 for symptomatic; P=0.008 and P=0.005 AU, respectively). Additionally, it was demonstrated that M2 macrophages from unstable plaques express cathepsin activity 5-fold higher than M2 macrophages from stable plaques (25.52 versus 5.22; P=0.008 AU). Conclusions-Targeting cathepsin activity in human carotid plaques may present a novel diagnostic tool for characterizing high-risk plaques. Novel cathepsin activity patterns within plaques and macrophage subpopulations suggest their involvement in the transition to active disease.

Original languageAmerican English
Pages (from-to)1101-1108
Number of pages8
JournalStroke
Volume47
Issue number4
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 American Heart Association, Inc.

Keywords

  • Activity-based probe
  • Atherosclerosis
  • Cathepsins
  • Macrophages
  • Optical imaging

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