During a heart attack, cells in the heart face an oxygen shortage followed by a strong immune response. In her PhD research at UMC Utrecht, Margarida Carmo Viola discovered how heart muscle cells communicate with each other during this process. She found that both low oxygen and inflammatory signals cause the cells to release more communication vesicles, but through different processes. These findings help us better understand how cell communication may influence damage during a heart attack.
Our cells are constantly communicating with each other. One way they do this is through extracellular vesicles (EVs): tiny particles that can contain proteins, genetic material, and other molecules. “What makes EVs particularly interesting is that they can carry messages not only to cells nearby,” says researcher Margarida Carmo Viola. “They can also travel through the bloodstream and potentially reach other parts of the body.”
During her PhD, Carmo Viola studied the role these vesicles may play during and after a heart attack. In particular, she focused on communication between human heart muscle cells and immune cells, something that is still not well understood.
A heart attack usually occurs when a coronary artery becomes blocked. Part of the heart then receives too little blood, depriving heart muscle cells of oxygen and nutrients. The cells become damaged and may eventually die.
This damage triggers a strong immune response. Immune cells move into the affected area to clear away dead cells and help start the repair process. This inflammation is necessary for recovery, but there is a delicate balance. If the inflammatory response becomes too strong or lasts too long, it can cause additional damage to the heart.
To understand what happens to cell communication under these conditions, Carmo Viola exposed human heart muscle cells to low oxygen levels and inflammatory signals in the laboratory. Both conditions caused the cells to release more EVs.
Although the outcome was similar, the processes behind it were different. “That was one of the most interesting findings for me,” says Carmo Viola. “Low oxygen and inflammation seemed to activate different pathways for producing and releasing these vesicles. How heart cells communicate may therefore depend on what is happening around them.”
Why heart muscle cells use different pathways is not yet clear. One possibility is that the different pathways also affect the message being sent. “The EVs may carry different molecules depending on what is happening to the cell,” Carmo Viola explains. “As a result, they may have different effects on the cells that receive them.”
These findings raise another question: if EVs play a role after a heart attack, could researchers eventually influence this communication? “You don’t want to completely stop inflammation, because you need it for recovery,” Carmo Viola explains. “But if EVs contribute to too much inflammation, it would be interesting to investigate whether we could influence their production.”
Before researchers can explore that possibility, there are still many questions to answer. “We first need to understand what messages these vesicles carry, where they travel, and what they do when they reach other cells.”
Her PhD also taught her how to deal with the uncertainty that comes with research. “I think I grew a lot as a scientist,” she says. “You learn how to formulate a hypothesis, test it, and find new ways to approach a problem, even when things don’t go as planned.”
