Rejuvenating the heart: new hope in the treatment of heart failure
Researchers from the Institute for Research and Innovation in Health at the University of Porto (i3S) and the Centre for Neuroscience and Cell Biology at the University of Coimbra (CNC-UC), part of the Centre for Innovation in Biomedicine and Biotechnology (CIBB), have made a discovery that could transform the future of cardiac medicine. Through an innovative strategy, inspired by anti-ageing medicine, the scientists have found a way to fight one of the most serious forms of heart failure: Heart Failure with Preserved Ejection Fraction (HFpEF).
In this condition, although the heart retains its ability to pump blood, the left ventricle loses the flexibility needed to relax and fill properly. The consequences are devastating: shortness of breath, crippling fatigue, limited ability to perform simple everyday tasks and, above all, a rate of mortality comparable to several types of cancer.
This form of heart failure is increasing at an alarming rate and, due to an ageing population, is expected to prevail in the near future. Its severity is exacerbated by the fact that it is often associated with other conditions, such as hypertension, diabetes, and obesity, thus making HFpEF one of the major challenges in contemporary cardiovascular medicine.
In this study, published in the journal Cardiovascular Research and highlighted in the editorial, researchers used an animal model that mimics human HFpEF in a cardiometabolic context and observed an accumulation of senescent cells in the immune system, blood vessels and heart. These are aged cells that have stopped dividing but remain in the body, releasing inflammatory substances that damage neighbouring tissue cells, thereby accelerating the ageing process and contributing to the development of disease.
“After administering a senolytic drug, which specifically eliminates these senescent cells, we observed simultaneous relief of multiple symptoms of HFpEF, indicating a direct impact on cardiovascular and systemic health,” says Diana S. Nascimento, coordinator of the i3S and ICBAS team.
Diana Nascimento (i3S and ICBAS) and Lino Ferreira (CNC-UC) led the work. Elsa Silva (i3S) and Inês Tomé (CNC-UC) are the first authors of the article now published.
“This work highlights the enormous potential of rejuvenation medicine as a therapeutic approach for complex and multifactorial diseases such as HFpEF,” explains researcher Lino Ferreira, leader of the team from CNC-UC/CIBB and the Faculty of Medicine of the University of Coimbra.
The researchers point out that elevated levels of senescent leukocytes (immune system cells) in circulation were observed in patients with HFpEF and were associated with greater disease severity, suggesting this approach may have direct clinical relevance.
“We are transforming the paradigm of cardiovascular therapy: it is not just a matter of relieving symptoms, but of acting directly on the cellular mechanisms of ageing, at the root of age-related organ dysfunction,” concludes Elsa Silva, i3S researcher and first author of the article.
The authors emphasise that the work “is a milestone in the convergence of anti-ageing and cardiovascular medicine, made possible only through strong collaboration between three leading Portuguese institutions in cardiovascular research, regenerative medicine and ageing: i3S, CNC-UC/CIBB and the Faculty of Medicine of the University of Porto (FMUP)”.
The teams are already planning their next steps towards evaluating the mechanisms behind premature cardiovascular ageing and developing new, more personalised therapies for future clinical translation.