La Marató finances three Vall d'Hebron projects in cardiovascular health

"La Marató" organised by 3Cat has presented the projects that will be financed thanks to the funds raised in the 2022 round, all of them dedicated to cardiovascular health. These 71 teams are carrying out 37 cardiovascular health projects in order to advance in the prevention, diagnosis and treatment of diseases that are the leading cause of death in developed countries. Among them are three led by the Cardiovascular Diseases Group and the Neurovascular Diseases Group of the Vall d'Hebron Research Institute.
The €11.2 million raised in the 2022 edition of La Marató, in addition to funding excellent scientific research, also raised awareness of cardiovascular diseases, which have a major impact on people's quality of life and life expectancy as they are the leading cause of death and hospital admissions in developed countries. In Catalonia alone, 45 people die every day, two every hour, as a result of a health problem in this area.

You can find out about VHIR's projects below:

The role of amino acid metabolism reprogramming and calpain dysregulation in fibroblast activation and diffuse myocardial fibrosis in heart failure.

A study led by Dr Javier Inserte, principal investigator of the Cardiovascular Diseases group at VHIR, in collaboration with Dr Arantxa González from the Foundation for Applied Medical Research (CIMA) in Pamplona, which received €300,000.

Heart failure (HF) is a complex and heterogeneous syndrome with a great socio-economic impact. Therefore, there is an urgent need to find new strategies focussed on alterations that cause heart dysfunction. Diffuse myocardial fibrosis (DMF), which refers to the excessive deposition of collagen within the cardiac tissue, is one of the main disorders found in patients with HF. Cardiac fibroblasts are the main promoters of DMF, but the mechanisms that modulate their activation and excessive collagen production are poorly characterised and no specific treatments are available.

Previous studies have shown that in chronic heart disease there is an increase in the transport of amino acids, i.e. the basic components of proteins, and an exaggerated activation of calpains, a family of proteases. However, little research has been done on the contribution of amino acid and calpain metabolism to the development of DMF. Based on preliminary data from the group, it is hypothesised that altered amino acid and calpain metabolism contributes to fibroblast activation, leading to the development of DMF and, ultimately, cardiac dysfunction and HF.
To test this hypothesis we propose to characterise alterations in the metabolism of amino acids and calpains, and their association with cardiac fibroblast activation, DMF and ventricular remodelling, in fibroblasts obtained from animal models* that reproduce characteristics of HF in humans, and in small samples of cardiac tissue obtained from patients with HF undergoing cardiac surgery. The potential for therapeutic interventions that modify the amino acid pattern to limit myocardial fibrosis and HF will also be assessed.

It is hoped that the knowledge generated by this multidisciplinary and innovative project will contribute to the design of new treatments to improve the life expectancy and quality of life of HF patients and to identify biomarkers with diagnostic potential.

Endovascular delivery of therapeutic nanomaterials for stroke recovery

Study led by Dr Anna Rosell, head of the Neurovascular Diseases group at VHIR, in collaboration with Dr Anna Roig's research group at the Institute of Materials Science of Barcelona (ICMAB), which has received €296,625.

Stroke occurs when a blood clot or thrombus blocks a cerebral artery (ischaemic stroke) or when an intracranial artery is blocked (haemorrhagic stroke) and causes cell death in specific areas of the brain. The only treatments available are thrombolytics for ischaemic strokes with tissue plasminogen activator to dissolve the clot or endovascular treatments for its mechanical removal. These treatments must be received within the first few hours after the onset of symptoms, which means that only around 15% of total strokes can be treated with these techniques. Therefore, there is an urgent need to investigate new treatments to protect the brain or repair damaged tissue.

In this context, new endovascular interventions could be very useful, as they use microcatheters to travel through the arterial blood system and remove the clots blocking the cerebral blood vessels. This system opens the door to new opportunities for directly accessing damaged brain areas and administering treatments through safe surgery. This project, called End-Stroke, proposes to take advantage of this clinical procedure to investigate the administration of therapeutic nanomaterials for the recovery of tissues affected by stroke in order to improve the delivery and arrival of therapeutic agents to the affected area of the brain.

Specifically, the team is interested in testing molecules with proven therapeutic actions in the recovery of brain cells in nanometric-sized capsules, known as nanocapsules. Administration through the blood vessels directly into the brain will help the treatment to reach the small cerebral vessels better, and the use of an external magnet will improve its retention in the damaged areas of interest. Researchers believe that this strategy, which will be tested in animal stroke models* in this project, will be useful in restoring the brain from stroke damage in a more effective way than if the treatment were administered freely to the general circulation.

Cardiovascular toxicity in early HER2-positive breast cancer: from risk assessment to prevention

A study led by Dr Ignacio Ferreira, head of the Cardiology Department at Vall d'Hebron University Hospital and head of the Cardiovascular Diseases group at VHIR, which received €198,125.

HER2-positive breast cancer (HERBCA) is the leading cause of cancer death in women. HER2 is a protein that confers the tumour an aggressive biological behaviour and a worse prognosis. Several drugs have so far been developed to block HER2, among which trastuzumab stands out as the first and most widely used against breast cancer. However, in addition to being expressed in breast cancer cells, HER2 is also expressed in myocardial (heart) cells, and it has been observed that in some cases, HER2-positive breast cancer treatment is associated with a high incidence of heart damage.

This damage to the heart can sometimes limit the therapy against the tumour and even cause death. The aim of the study is to diagnose cardiotoxicity at an early stage by using analytical markers of cardiac damage (troponin) and cardiac imaging techniques (echocardiography and cardiac magnetic resonance imaging). Furthermore, the aim is to study the association of these alterations with progression to more advanced stages of cardiotoxicity, such as the appearance of left ventricular dysfunction, which can lead to heart failure.

It will also assess how some possible cardioprotective drugs, such as beta-blockers or ACE inhibitors, can attenuate the progression of cardiotoxicity from the initial stages to the development of cardiac dysfunction. At the same time, the study aims to demonstrate whether there is a certain genetic predisposition to the development of cardiotoxicity and will delve deeper into the physiopathological mechanisms involved in the toxicity of the heart.

*Institutional Declaration on the use of animal research