The Silent Threat: Impact of Acute and Latent Viral Infections on Development and Outcomes of Ischemic Heart Disease

Project title: The Silent Threat: Impact of Acute and Latent Viral Infections on Development and Outcomes of Ischemic Heart Disease

Acronym: VIRAL-COR

Call title: Installation Research Projects

Call code: UIP-2026

Funding source: Croatian Science Foundation

Applicant name: University of Rijeka, Faculty of Medicine, Marko Šustić, MD, PhD

Coordinator: Marko Šustić, MD, PhD

Research Team, University of Rijeka, Faculty of Medicine:

  • Ivana Smoljan, MD, PhD
  • Iva Vladić, MD, PhD student

Project implementation period: 30.12.2026 – 29.12.2029

Total project value: EUR 200.000,00

Brief description:

Ischemic heart disease remains the leading global cause of morbidity and mortality. In recent decades, research has increasingly viewed its development, progression, and outcomes through the lens of immune system dynamics and inflammatory processes. Viral infections and environmental antigens profoundly shape the mammalian immune system, thereby exerting significant influence on cardiovascular health.

Epidemiological evidence strongly links latent cytomegalovirus infection to worse outcomes after myocardial infarction and associates the peri-influenza period with heightened acute coronary syndrome incidence. Recently, we investigated the effects of latent cytomegalovirus on the heart in a murine model. Through a combination of cellular and functional techniques, we found that latent murine cytomegalovirus infection is associated with substantial changes in the cardiac immune cell composition, increased inflammatory responses after myocardial infarction, and pronounced adverse cardiac remodelling. Furthermore, in a cohort of human subjects after myocardial infarction, cytomegalovirus latency was associated with poorer recovery of left ventricle systolic function.

The first goal of this project is to examine cytomegalovirus-driven inflammatory changes in a human cohort of patients during the reparative phase of myocardial infarction. We will next identify and characterize the cardiac cell populations that harbor latent cytomegalovirus in murine cardiac tissue. Cytomegalovirus establishes lifelong latency in a large part of human population and modulates immune responses to other viruses. We will therefore investigate how acute influenza infection affects myocardial infarction occurrence and outcomes, both in the absence and presence of latent cytomegalovirus. Using a murine model with genetic predisposition to atherosclerosis and myocardial infarction, we will assess whether acute influenza exacerbates inflammatory and structural cardiac damage and determine potential adverse interactions between influenza and latent cytomegalovirus.

Through high-throughput cellular, molecular, and imaging approaches, this project will delineate how acute and chronic viral infections, individually and together, modulate immune responses and healing in the infarcted heart.