Heart surgeries, such as coronary artery bypass grafting or bypass, are life-saving procedures for patients with advanced coronary artery disease. However, even after the most precise procedures, patients often face a lengthy recovery period and the risk of complications. How do you check if the healing process is going well? Can problems be predicted before they occur?

**Dr. Anna Lemańska-Perek**, **Dr. Dorota Krzyżanowska-Gołąb**, Department of Biochemistry and Immunochemistry, and **Dr. habil. Barbara Adamik**, Professor at Wroclaw Medical University, Department and Clinic of Anesthesiology and Intensive Care

**Dr. Anna Lemańska-Perek**, **Dr. Dorota Krzyżanowska-Gołąb**, Department of Biochemistry and Immunochemistry, and **Dr. habil. Barbara Adamik**, Professor at Wroclaw Medical University, Department and Clinic of Anesthesiology and Intensive Care

The answers may lie in fibronectin, a protein that, although well known to scientists, has only recently begun to reveal its full potential. In a study entitled “Changes in various forms of fibronectin in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass - a prospective, observational study,” published in the group's journal Nature Scientific Reports, Anna Lemańska-Perek, PhD of the Department of Biochemistry and Immunochemistry at the Wroclaw Medical University, shed new light on the role of this protein in regenerative and inflammatory processes in the heart.

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Fibronectin - the architect of the extracellular matrix

Fibronectin is an extracellular matrix protein. It forms a "scaffold" for cells in the body, providing them with mechanical support and enabling them to communicate with the environment. This protein is key in many biological processes, such as wound healing, tissue repair, and inflammatory reactions. Its role in the body depends on its form and the biological context in which it acts.

Under natural conditions, fibronectin exists in two primary forms:

1. Plasma FN is produced in the liver and circulates in blood plasma, supporting clotting and tissue regeneration. Fibronectin in this form binds to fibrin, helping to stabilize the clot and accelerate the repair of damaged blood vessels.

2. Cellular FN - produced locally by various cell types, including fibroblasts, plays a unique role at sites of injury and inflammation.

Cellular fibronectin in plasma is absent or present in tiny amounts in a healthy body. Its production increases rapidly in response to stress, such as trauma, infection, or surgery. This form of the protein plays a special, albeit ambivalent, role in regenerative and inflammatory processes.

While the appearance of cellular fibronectin is necessary for the proper start of repair processes - such as closing wounds and rebuilding damaged structures - an excess can lead to negative consequences. Chronic elevation of its levels contributes to tissue fibrosis, which means excessive deposition of its elements, such as collagen, leading to increased tissue stiffness and dysfunction.

"The appearance of cellular fibronectin in the early stages of healing is a normal, physiological phenomenon indicating the activation of repair processes. The alarming phenomenon is the persistence of high levels of it for a more extended period after injury," explains Dr. Lemanska-Perek.

These dynamic changes in fibronectin levels, especially its cellular form, are key to understanding how the body copes with injury. For example, during heart surgery, when tissue damage and strong inflammatory processes are activated, this protein acts as both a mediator of regeneration and a potential risk factor for long-term complications such as heart failure.

That's why monitoring fibronectin levels—particularly its cellular form—may become an essential diagnostic tool, allowing doctors to predict better the course of patients' recovery after major surgery.

Biological compass of heart regeneration

The study, conducted by researchers and clinicians at the Wroclaw Medical University, included 40 patients undergoing coronary artery bypass graft surgery using extracorporeal circulation. Although the operation is one of the most common life-saving procedures for advanced coronary artery disease, it is associated with triggering a strong inflammatory response in the body, which plays a key role in healing and tissue regeneration processes.

During the study, we measured the levels of two forms of fibronectin, plasma and cellular, at different time points before and after surgery. The results revealed significant changes:

Plasma fibronectin levels dropped sharply in the first few hours after surgery, reaching their lowest level after 6 hours. Then, over the next 18 hours, they gradually returned to baseline values. This decline reflected the involvement of this form of the protein in repair processes, such as clot stabilization and reconstruction of damaged vessels.

On the contrary, levels of cellular fibronectin steadily increased during the first 24 hours after surgery. This phenomenon indicated activation of regenerative processes such as tissue reconstruction and extracellular matrix remodeling, but it also signaled activation of the immune system and inflammation.

These changes are key to understanding how the body responds to surgical trauma and what repair mechanisms it activates.

The researchers also noted that increased levels of cellular fibronectin were particularly relevant to the risk of postoperative complications.

Sustained high levels of this form over the long term may signal abnormal repair processes, such as fibrosis, which leads to increased cardiac stiffness and deterioration of cardiac function. These data confirm that fibronectin, especially its cellular form, is a biological compass to assess whether the healing process progresses. Its levels can indicate when the body is moving toward healing and when medical intervention is needed.

In addition, the study showed that the duration of extracorporeal circulation significantly affected cellular fibronectin levels, indicating the need to minimize the length of this stage of surgery to reduce the severity of the inflammatory response and improve healing outcomes.

New diagnostic possibilities

One of the study's goals was to see if cellular fibronectin could be used as a biomarker in regenerative medicine. The results indicate significant potential in this regard. Fibronectin could enable better monitoring of repair processes after injury or surgery. However, introducing this method into clinical practice requires further research and technological improvements. As Dr. Anna Lemańska-Perek notes:

"Work is underway to inhibit fibrosis processes after injury using synthetic peptides that inhibit fibronectin polymerization on the cell surface. These are still early-stage studies."

At the same time, differences in cellular fibronectin levels between patients open up the possibility of personalizing treatment. Collected data show that people with certain chronic diseases, such as atherosclerosis, diabetes, or obesity, exhibit higher levels of this protein, which may affect inflammatory and regenerative processes. As Dr. Lemańska-Perek explains:

"Changes in fibronectin levels, especially in the cellular form, are observed in inflammatory processes, and we observe them in patients with atherosclerosis, diabetes, cancer, or sepsis."

These observations underscore the potential of this protein not only as an indicator of bodily processes but also as a tool for developing more precise therapies tailored to individual patient needs.

Therapies based on precise diagnostics

Cellular fibronectin and its key role in regenerative processes after heart surgery may be necessary in other inflammatory conditions, such as sepsis and multi-organ trauma. In a study led by Dr. Anna Lemańska-Perek with coworkers, it was shown that elevated levels of the cellular form and reduced plasma levels correlate with a more severe course of sepsis. Additionally, in COVID-19-induced sepsis, high levels of the cellular form of fibronectin were associated with a higher risk of patient death.

Notably, the sepsis study used artificial intelligence-based models to identify the parameters that greatly impacted patient survival. Plasma fibronectin just turned out to be one of the key indicators. This shows how modern technology can support biomedical research, speeding up diagnosis and enabling more effective interventions.

However, fibronectin provides valuable diagnostic information and opens the way to new therapies. Understanding the mechanisms of its fragmentation and formation of complexes with fibrin may contribute to developing targeted therapies. As Dr. Lemańska-Perek points out:

"Determination of fragments and complexes requires Western Blotting, which increases the time waiting for the final result. Nevertheless, it is a starting point for searching for specific fibronectin-degrading proteases and developing a rapid test for their detection."

Future therapies could modulate fibronectin activity by inhibiting its pathological polymerization or reducing excessive fragmentation. This approach could reduce the adverse effects of chronic inflammation, such as tissue fibrosis, and increase the chances of successful recovery from serious injuries.

Responses at the heart of the cell

Research on fibronectin is just the beginning. With its ability to modulate regenerative processes, fibronectin, and its cellular form could become a key tool in monitoring and treating patients after heart surgery.

What begins as a protein study in the lab has the potential to turn into a breakthrough in medicine - a better understanding of healing processes and the ability to control them precisely. We are entering an era where biomarkers such as fibronectin can help doctors see more, act faster, and treat more effectively. The future may be closer than we think.

D. Sikora

FAQ: Fibronectin

What was the main goal of the study?

The study analyzes changes in various forms of fibronectin, a key extracellular matrix component, in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). The researchers aim to understand how these changes are linked to the inflammatory response and repair processes associated with the procedure.

How does CPB affect fibronectin levels?

The study found that CPB leads to:

A decrease in pFN levels during the procedure, which returns to baseline within 24 hours.
An increase in EDA-FN levels during the first 24 hours post-surgery.

Why is EDA-FN considered a marker of tissue damage and repair?

EDA-FN acts as a damage-associated molecular pattern (DAMP) released in response to tissue injury. It can trigger inflammatory responses and contribute to initiating repair processes. The observed increase in EDA-FN levels post-surgery, mainly linked to CPB duration, confirms its role in these processes.

How do fibronectin fragments reflect the body’s response to CABG?

Fibronectin fragments, formed through proteolytic degradation by enzymes such as urokinase and cathepsin G, were found in patients and healthy volunteers. This suggests that their presence may be related to degradation due to aging. However, specific types and levels of fragments could provide additional information about inflammatory responses and tissue repair dynamics following CABG.

What are the two primary forms of fibronectin, and where are they present?

Fibronectin exists in two primary forms:

Plasma fibronectin (pFN): This soluble form is synthesized by hepatocytes and circulates in the blood plasma.
Cellular fibronectin (EDA-FN): This insoluble form is produced by various cells and is a component of the extracellular matrix.

What factors influence changes in pFN levels after surgery?

Multifactorial analysis revealed that the main factors influencing pFN levels 6 and 12 hours after surgery were a history of hypertension and the duration of CPB.

What is the significance of fibronectin-fibrin complexes in CABG patients?

Fibronectin-fibrin complexes were detected in all CABG patients but not in healthy volunteers. These complexes indicate the activation of the coagulation process, likely related to endothelial damage occurring during the procedure.

What are the main conclusions of the study regarding fibronectin and CABG?

The study demonstrated that changes in pFN and EDA-FN levels during CABG are markers of the inflammatory response triggered by the procedure. The extent of these changes is associated with the duration of CPB and the presence of pre-existing conditions such as hypertension. The findings suggest that monitoring various forms of fibronectin could help assess the intensity of the inflammatory response and the progress of repair processes in CABG patients.