Molecular Hallmarks of Ischemia with Non-Obstructive Coronary Arteries: The “INOCA versus Obstructive CCS” Challenge

Alice Bonanni, Alessia D’Aiello, Daniela Pedicino, Marianna Di Sario, Ramona Vinci, Myriana Ponzo, Pellegrino Ciampi, Denise Lo Curto, Caterina Conte, Francesco Cribari, Francesco Canonico, Giulio Russo, Rocco Antonio Montone, Carlo Trani, Anna Severino, Filippo Crea, Giovanna Liuzzo

Risultato della ricerca: Contributo in rivistaArticolo in rivista


Up to 4 million patients with signs of myocardial ischemia have no obstructive coronary artery disease (CAD). The absence of precise guidelines for diagnosis and treatment in non-obstructive CAD encourages the scientific community to fill the gap knowledge, to provide non-invasive and less expensive diagnostic tools. The aim of our study was to explore the biological profile of Ischemia with Non-Obstructive Coronary Arteries (INOCA) patients with microvascular dysfunction compared to patients presenting with obstructive chronic coronary syndrome (ObCCS) in order to find specific hallmarks of each clinical condition. We performed a gene expression array from peripheral blood mononuclear cells (PBMCs) isolated from INOCA (n = 18) and ObCCS (n = 20) patients. Our results showed a significantly reduced gene expression of molecules involved in cell adhesion, signaling, vascular motion, and inflammation in INOCA as compared to the ObCCS group. In detail, we found lower expression of Platelet and Endothelial Cell Adhesion Molecule 1 (CD31, p < 0.0001), Intercellular Adhesion Molecule-1 (ICAM1, p = 0.0004), Tumor Necrosis Factor (TNF p = 0.0003), Transferrin Receptor (TFRC, p = 0.002), and Vascular Endothelial Growth Factor A (VEGFA, p = 0.0006) in the INOCA group compared with ObCCS. Meanwhile, we observed an increased expression of Hyaluronidase (HYAL2, p < 0.0001) in INOCA patients in comparison to ObCCS. The distinct expression of molecular biomarkers might allow an early and non-invasive differential diagnosis between ObCCS and INOCA, improving clinical management and treatment options, in the era of personalized medicine.
Lingua originaleEnglish
pagine (da-a)1711-N/A
RivistaJournal of Clinical Medicine
Stato di pubblicazionePubblicato - 2022


  • Biomarker
  • Chronic coronary syndromes (CCS)
  • Coronary microvascular dysfunction (CMD)
  • Gene expression
  • Ischemia with non-obstructive coronary artery (INOCA)
  • Non-obstructive CAD
  • Precision medicine


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