Strong Hearts

Heart muscle cells are large compared to most of the other cells in the body. And they are very sluggish when it comes to dividing. “Cell division is an arduous process,” says cardiologist Carolin Lerchenmüller, “and cells with the structure and size of heart muscle cells don’t really want to do it.” This has consequences, because when they break down, for example when a person has a heart attack, they tend not to be replaced by new cells, but by scar tissue (fibrosis). This causes the tissue to harden and lose some of its function, impacting the cells’ ability to conduct electrical signals and their contractility. In other words, the cells are less able to contract, weakening the performance of the heart. 

The performance of damaged hearts could be improved if the heart muscle cells were actually able to regenerate, and this is precisely what Lerchenmüller is exploring in her basic research with mice. They are put through their paces by running around a wheel, for example. And the conclusion is that, after eight weeks of training, these mice were found to have formed new heart muscle cells. “The number of new cells isn’t huge,” says Lerchenmüller, “but the key finding is that myocardial tissue can regenerate itself. This immediately begs the question: how can we initiate or support this process?”

The obvious answer is with sporting activity. Or with biochemical stimuli. “We’ve already identified factors that protect the heart,” says Lerchenmüller, the first professor of gender medicine at UZH. These include certain microRNA (small, non-coding ribonucleic acid molecules) and the protein CITED4, for example. “This protein is produced in greater quantities in the heart muscle cells when sporting activity takes place. And it can protect the heart from damage, at least it can in mice,” says Lerchenmüller. Conversely, Lerchenmüller was able to demonstrate that, if the protein is lacking and the heart is damaged or placed under great strain by sporting activity, this weakens the heart. These findings are currently undergoing preclinical trials, for example involving gene-therapy interventions where the gene is planted in the heart muscle cells with the blueprint for the CITED4 protein. 

Can this research in mice be applied to human beings? And why is it so important for women in particular? Cardiology plays a leading role in gender medicine because women’s hearts and men’s hearts develop differently. For example, on average women tend to develop coronary heart disease later in life, but they are more likely to die of it than men. Cardiovascular diseases are the most common cause of death among women (49 percent), with coronary heart disease at the top of the list. 

Another problem is diagnosing heart attacks. As women frequently have different symptoms to men, a heart attack is not recognized or is sometimes only diagnosed later on. “There’s still plenty of work to do,” adds Lerchenmüller. This is also true in her research, as some of the basic scientific research she has conducted has been on male mice only. “Sometimes it’s not possible, especially with very complicated and expensive methods, to incorporate all the variables right from the start. This includes those that may be triggered by female sex hormones,” says Lerchenmüller. There is a certain justification to this approach. “When you’re just starting a research assignment, the first thing you need to do is understand the basic mechanisms of action. And there must always be very good reasons for choosing the number of animals that are used,” says Lerchenmüller. But the cardiologist reiterates that on the whole, it is very important to consider the aspect of gender. 

This is why she is involved in several projects that also focus primarily on differences between sexes. One example of how the findings obtained from basic research could have clinical applications is chemotherapies used to treat cancer. The drugs that attack the cancer cells also damage the heart muscle cells. This is what happens, for example, when breast cancer is treated with chemotherapy, which is also frequently used on young women. “We now know that many women who survive breast cancer go on to die of heart failure,” says Lerchenmüller. “So we need to ask ourselves: how can we protect the heart and yet still fight the cancer?”

Lerchenmüller suggests that a delicate balance of targeted therapies is required. “We know that sport protects the heart and at the same time helps to fight cancer. This is of course the perfect combination.” Ideally, the positive effects that sport induces within the heart could be supported with therapeutic interventions based on Lerchenmüller’s research at a molecular level. “I hope that our work can lay the foundation that will allow us to strengthen the heart, particularly in situations that are stressful for the body, such as chemotherapy. It would be even better if this could be done as a preventative measure.” There’s still plenty of work to do. But the work has started. 

This article is part of the dossier on gender medicine from UZH Magazine 1/24.