Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery

Lucas M. Ferrer, Alexandra M. Monroy, Jahaira Lopez-Pastrana, Gayani Nanayakkara, Ramon Cueto, Ya feng Li, Xinyuan Li, Hong Wang, Xiao feng Yang, Eric T. Choi

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase−/− mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase−/− mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase−/− tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalJournal of Cardiovascular Translational Research
Volume9
Issue number2
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Keywords

  • Caspase-1
  • Chronic kidney disease (CKD)
  • Neointimal hyperplasia (NH)
  • Vascular inflammation
  • Vascular smooth muscle cell (VSMC)

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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