Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion

Daniela Pedicino, Ramona Vinci, Ada F. Giglio, Eugenia Pisano, Italo Porto, Rocco Vergallo, Giulio Russo, Aureliano Ruggio, Alessia D'Aiello, Davide Flego, Gianmarco Annibali, Francesco Trotta, Roberto Piacentini, Giampaolo Niccoli, Giovanna Liuzzo, Filippo Crea

Research output: Contribution to journalArticle

Abstract

Background: Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown. Objectives: The authors sought to assess the role of hyaluronan (HA) metabolism in ACS. Methods: Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis. Results: Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively). Conclusions: HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability.

Original languageEnglish
Pages (from-to)1490-1503
Number of pages14
JournalJournal of the American College of Cardiology
Volume72
Issue number13
DOIs
Publication statusPublished - Sep 25 2018

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Keywords

  • ACS
  • hyaluronan
  • inflammation
  • intact fibrous cap
  • OCT
  • personalized medicine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pedicino, D., Vinci, R., Giglio, A. F., Pisano, E., Porto, I., Vergallo, R., Russo, G., Ruggio, A., D'Aiello, A., Flego, D., Annibali, G., Trotta, F., Piacentini, R., Niccoli, G., Liuzzo, G., & Crea, F. (2018). Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion. Journal of the American College of Cardiology, 72(13), 1490-1503. https://doi.org/10.1016/j.jacc.2018.06.072