February Researchers identify new model to develop treatments for heart attack

CÚRAM SFI Research Centre for Medical Devices researchers have published in Nature Communications a key study establishing a new pre-clinical model to develop clinically relevant treatments for heart attacks. 

Heart attacks (myocardial infarction (MI)) occur due to an acute complication of coronary artery disease and are a major cause of global mortality. The two main types of heart attack are ST-elevation (STEMI) and Non-ST elevation (NSTEMI). A non-ST-elevation is a type of heart attack that usually happens when your heart's oxygen needs are unmet. This condition gets its name because it doesn't have an easily identifiable electrical pattern like with an ST elevation that can be read from an electrocardiogram (ECG).

Patients who survive a heart attack have variable degrees of damage to their cardiac tissue, which can lead to heart failure in a significant proportion of these patients. In the last two decades, NSTEMIs have markedly risen in hospitalised patients. This subtype of heart attack results in a smaller amount of tissue damage compared to STEMIs. Still, importantly, recent clinical registry data shows that NSTEMIs are associated with higher long-term mortality than STEMIs.

Currently, preclinical models of heart attack mimic only full-thickness STEMI and hence cater only for an investigation into therapeutics and interventions directed at the NSTEMI subset of heart attack. In this new study, researchers have developed a preclinical model of NSTEMI by adopting a novel surgical procedure that closely resembles the complexity of clinical cases in humans. Researchers validated the presented model by comparing it with an established method to achieve STEMIs. They performed a detailed analysis at the main acute and late time points after the induction of NSTEMI, at 7 and 28 days, respectively. 

Dr Paolo Contessotto and Dr Renza Spelat said: "Advanced analyses on the affected heart tissue highlighted a distinctive pattern of alterations in the tissue, especially in the sugar moieties (glycans) which compose cardiac cell membranes and extracellular matrix (the network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body). Identifying such changes in molecular elements that can be accessed and treated with injectable drugs sheds light on how we can develop targeted pharmacological solutions to correct these changes."

This research resulted from an established collaboration of CÚRAM with European institutions in Italy (University of Milano-Bicocca), France (University of Paris Est Créteil), Sweden (University of Gothenburg) and Lithuania (Lithuanian University of Health Sciences).

Professor Abhay Pandit, CÚRAM Scientific Director and senior author of the study, said: "There is a need in the field to adopt clinically relevant models to study NSTEMI pathophysiology and reveal its functional differences with STEMI induction. This new model will facilitate the translation of future research in the field, enabling the discovery of new clinically relevant treatments for patients."

Mr Mark Da Costa, Clinical Investigator at CÚRAM and senior author of the study, said: "Currently, NSTEMI is the most common presentation of acute heart attack. The concern is that NSTEMI patients have lower in-patient (during their admission for the primary NSTEMI) and short-term mortality rates but significantly higher long-term mortality than those of STEMI patients. A Danish registry study of 8,889 patients showed that the 5-year mortality after NSTEMI was 16%, and another registry study highlighted a 10-year survival rate of only around 50%. To the best of our knowledge, there are currently no models that can reproduce both the functional and histological characteristics of NSTEMIs. This novel model may specifically serve as a preclinical foundation to study interventions that could combat the short and long-term effects of NSTEMI."

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Notes for editors

Link to complete manuscript: https://rdcu.be/c6apm

Nature Communications volume 14, Article number: 995 (2023)

This study was funded by the European Commission funding under the AngioMatTrain 7th Framework Programme (Grant Agreement Number 317304) and by the research grant from Science Foundation Ireland (SFI) co-funded under the European Regional Development Fund under Grant Number 13/RC/2073 and13/RC/2073_P2 to A.P

About CÚRAM

CÚRAM, the SFI Research Centre for Medical Devices, is developing the next generation of medical devices and training a highly-skilled workforce. Set up in 2015, CÚRAM is now a world-leading Irish Medical Device R&D Centre based out of NUI Galway. While led by University of Galway, CÚRAM's partner institutes include University College Dublin, University College Cork, Trinity College Dublin, University of Limerick, Royal College of Surgeons Ireland, Dublin City University, Technological University of the Shannon, National Institute Bioprocessing Research and Training and Technological University Dublin. The Centre focuses on developing biomedical implants and therapeutic and diagnostic devices that address the needs of patients with chronic illnesses. They also partner with local small-and-medium enterprises (SMEs) and multinational medical device and pharmaceutical companies to increase employment in Ireland. The Centre has seen numerous scientific breakthroughs as researchers focus on improving the quality of life for patients living with long-term chronic conditions such as diabetes, back pain, cardiovascular disease and stroke. Our researchers focus on engineering approaches for repair and remodelling, improved drug delivery solutions and superior medical implant designs to treat chronic diseases. CÚRAM was created because clinicians, industry, and researchers need to collaborate in developing medical devices that will create jobs and establish a global hub for MedTech. Follow us @CURAMdevices or visit www.universityofgalway.ie/curam