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

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Myocardial ischemia affects millions, with many lacking obstructive coronary artery disease (CAD).
• Current diagnostic and treatment guidelines for non-obstructive CAD are lacking, necessitating research into non-invasive tools.
• Understanding the biological differences in Ischemia with Non-Obstructive Coronary Arteries (INOCA) is crucial for advancing patient management.

Purpose of the Study:

• To compare the gene expression profiles of INOCA patients with microvascular dysfunction against patients with obstructive chronic coronary syndrome (ObCCS).
• To identify specific molecular hallmarks that differentiate INOCA from ObCCS.
• To explore potential non-invasive diagnostic biomarkers for these conditions.

Main Methods:

• Gene expression arrays were performed on peripheral blood mononuclear cells (PBMCs).
• PBMCs were isolated from two patient groups: INOCA (n=18) and ObCCS (n=20).
• Differential gene expression analysis was conducted to identify significant molecular variations.

Main Results:

• INOCA patients exhibited significantly reduced expression of genes involved in cell adhesion, signaling, vascular motion, and inflammation compared to ObCCS patients.
• Specific molecules with lower expression in INOCA included CD31, ICAM1, TNF, TFRC, and VEGFA.
• Conversely, INOCA patients showed increased expression of Hyaluronidase (HYAL2) compared to the ObCCS group.

Conclusions:

• Distinct molecular biomarker profiles exist between INOCA and ObCCS patients.
• These molecular differences offer potential for early and non-invasive differential diagnosis.
• Identifying these hallmarks can improve clinical management and treatment strategies within personalized medicine.