Tetiana Motsak

Bogomolets National Medical University

Title: Matrix Metalloproteinases and Serotonin as Biomarkers in Patients with Multifocal Atherosclerosis

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Biography

Tetiana Motsak, MD, PhD, is an Associate Professor in the Department of Internal Medicine at Bogomolets National Medical University in Kyiv, Ukraine, and an EAS Young Fellow (2026–2028). She also holds a Master's degree in Pedagogy and serves as a sub-investigator in clinical trials, combining clinical practice, medical education, and research administration. Her clinical and scientific expertise is reflected in her active membership in the European Society of Cardiology (ESC), the European Atherosclerosis Society (EAS), and the European Lipoprotein Club (ELC). Dr. Motsak's research focuses on cardiovascular disease and translational medicine, with a particular interest in atherosclerotic plaque biology. Most recently, she was a visiting scientist at the University Medical Center Utrecht, the Netherlands, where she contributed to advanced research on plaque morphology using the Athero-Express biobank. With more than a decade of experience spanning clinical medicine, research, and higher medical education, she is dedicated to fostering international academic collaborations and advancing evidence-based cardiovascular care through innovative research and excellence in teaching.

Abstract

Introduction: Multifocal atherosclerosis (MAS) is an advanced manifestation of systemic atherosclerotic disease involving multiple arterial territories and is associated with a markedly increased risk of recurrent cardiovascular events. Matrix metalloproteinases (MMP-2 and MMP-9) contribute to extracellular matrix degradation and plaque destabilization, whereas serotonin promotes platelet activation, vascular inflammation, and thrombosis. The combined assessment of these circulating biomarkers may improve the evaluation of disease activity and therapeutic response in MAS.

Objective: To investigate circulating serotonin, MMP-2, and MMP-9 levels in patients with multifocal atherosclerosis and evaluate their changes following adjunctive therapy.

Methods:  The study included 84 men (68.4 ± 5.8 years) with clinically confirmed MAS and intermittent claudication syndrome (ICS). Group 1 included 40 patients with previous myocardial infarction (>12 months before enrollment), and Group 2 included 44 patients with previous ischemic stroke (>12 months before enrollment). Eighteen age-matched healthy men served as controls. Plasma serotonin, MMP-2, and MMP-9 concentrations were measured by ELISA. Doppler ultrasonography was used to assess volumetric blood flow in the internal carotid, common femoral, and posterior tibial arteries. In addition to standard secondary prevention therapy, all patients received cilostazol and gamma-aminobutyric acid for 16 weeks.

Results: Compared with healthy controls, baseline serotonin concentrations were 3.8-fold higher, while MMP-2 and MMP-9 levels were increased by 57% and 64%, respectively (all p<0.001). Biomarker levels did not differ significantly between patients with previous myocardial infarction and ischemic stroke. Volumetric blood flow was significantly reduced in all examined arteries in both MAS groups (all p<0.01). After 16 weeks of therapy, serotonin and MMP-2 levels significantly decreased in both groups (both p<0.001), whereas MMP-9 declined significantly only in patients with previous myocardial infarction (p<0.05). These changes were accompanied by significant improvements in arterial blood flow (all p<0.05).

Conclusion: Patients with multifocal atherosclerosis demonstrate elevated circulating serotonin and MMP-2/-9 levels. Following adjunctive therapy, reductions in these biomarkers were accompanied by improved arterial blood flow, supporting their potential utility for monitoring disease activity and treatment response.