Coronary artery plaque rupture and erosion: Role of wall shear stress profiling and biological patterns in acute coronary syndromes

Giulio Russo, Daniela Pedicino, Claudio Chiastra, Ramona Vinci, Maurizio Lodi Rizzini, Lorenzo Genuardi, Mohammad Sarraf, Alessia d'Aiello, Marco Bologna, Cristina Aurigemma, Alice Bonanni, Antonio Bellantoni, Fabrizio D'Ascenzo, Pellegrino Ciampi, Aniello Zambrano, Luca Mainardi, Myriana Ponzo, Anna Severino, Carlo Trani, Massimo MassettiDiego Gallo, Francesco Migliavacca, Francesco Maisano, Amir Lerman, Umberto Morbiducci, Francesco Burzotta, Filippo Crea, Giovanna Liuzzo

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Wall shear stress (WSS) is involved in coronary artery plaque pathological mechanisms and modulation of gene expression. This study aims to provide a comprehensive haemodynamic and biological description of unstable (intact-fibrous-cap, IFC, and ruptured-fibrous-cap, RFC) and stable (chronic coronary syndrome, CCS) plaques and investigate any correlation between WSS and molecular pathways. Methods and results: We enrolled 24 CCS and 25 Non-ST Elevation Myocardial Infarction-ACS patients with IFC (n = 11) and RFC (n = 14) culprit lesions according to optical coherence tomography analysis. A real-time PCR primer array was performed on peripheral blood mononuclear cells for 17 different molecules whose expression is linked to WSS. Computational fluid dynamics simulations were performed in high-fidelity 3D-coronary artery anatomical models for three patients per group. A total of nine genes were significantly overexpressed in the unstable patients as compared to CCS patients, with no differences between IFC and RFC groups (GPX1, MMP1, MMP9, NOS3, PLA2G7, PI16, SOD1, TIMP1, and TFRC) while four displayed different levels between IFC and RFC groups (TNFα, ADAMTS13, EDN1, and LGALS8). A significantly higher WSS was observed in the RFC group (p < 0.001) compared to the two other groups. A significant correlation was observed between TNFα (p < 0.001), EDN1 (p = 0.036), and MMP9 (p = 0.005) and WSS values in the RFC group. Conclusions: Our data demonstrate that IFC and RFC plaques are subject to different WSS conditions and gene expressions, suggesting that WSS profiling may play an essential role in the plaque instability characterization with relevant diagnostic and therapeutic implications in the era of precision medicine.

Original languageEnglish (US)
Pages (from-to)356-365
Number of pages10
JournalInternational Journal of Cardiology
Volume370
DOIs
StatePublished - Jan 1 2023

Keywords

  • Acute coronary syndrome
  • Computational fluid dynamics
  • Personalized medicine
  • Plaque erosion
  • Plaque rupture
  • Shear stress
  • Vulnerable plaque

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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