Personalized treatment for heart failure?

Personalized treatment for heart failure?

Heart Failure (HF) is characterized by a malfunction of the heart in supplying the body with enough blood for the proper working of its organs. In Spain over 3% of the adult population presents with HF, but this figure is on the rise due to the ageing population and the increase in the prevalence of heart diseases producing HF.

The researcher points out that, "In view of this challenge, on the one hand existing healthcare resources must be optimized in order to reduce the number of new cases and improve the prognosis and quality of life of HF patients, and, on the other, to research the mechanisms that produce heart failure in order to develop treatments that are more effective and safe that the ones that exist at present".

In the article the researchers show that an excess of a molecule (lysyl oxidase-like 2) produces fibrosis of the cardiac muscle, which impedes its normal functioning and stimulates the development of HF. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration.

In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions.

In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF. "These results suggest that the lysyl oxidase-like 2 enzyme may be a target for the treatment of this disease", said the author.

Once the activity of the enzyme has been described, the next step is to develop tests for a precise diagnosis of patients with heart disease who present an excess of this molecule in their hearts. These tests will be carried out at CIMA and the Clínica Universidad de Navarra by the BIOMARCS research group, a pioneering team in the research of cardiac biomarkers for HF patients.

Additionally, drugs to inhibit this molecule for the personalized treatment of each patient will be developed. As author states, "This strategy may be particularly valuable in the 50% of heart failure cases for which there is no effective treatment at present. In these patients, the change in the performance of the heart is closely related to fibrosis of the cardiac muscle, and so the suppression of this enzyme is proposed as a very promising therapeutic alternative".