Post-Genomic Methodologies and Preclinical Animal Models: Chances for the Translation of Cardioprotection to the Clinic

Abstract

Although many cardioprotective strategies have demonstrated benefits in animal models of myocardial infarction, they have failed to demonstrate cardioprotection in the clinical setting highlighting that new therapeutic target and treatment strategies aimed at reducing infarct size are urgently needed. Completion of the Human Genome Project in 2001 fostered the post-genomic research era with the consequent development of high-throughput “omics” platforms including transcriptomics, proteomics, and metabolomics. Implementation of these holistic approaches within the field of cardioprotection has enlarged our understanding of ischemia/reperfusion injury with each approach capturing a different angle of the global picture of the disease. It has also contributed to identify potential prognostic/diagnostic biomarkers and discover novel molecular therapeutic targets. In this latter regard, “omic” data analysis in the setting of ischemic conditioning has allowed depicting potential therapeutic candidates, including non-coding RNAs and molecular chaperones, amenable to pharmacological development. Such discoveries must be tested and validated in a relevant and reliable myocardial infarction animal model before moving towards the clinical setting. Moreover, efforts should also focus on integrating all “omic” datasets rather than working exclusively on a single “omic” approach. In the following manuscript, we will discuss the power of implementing “omic” approaches in preclinical animal models to identify novel molecular targets for cardioprotection of interest for drug development.

The platelet paradox of injury versus protection in myocardial infarction—has it been overlooked?

“…Undoubtedly, this retrospective analysis touches upon a topic of high clinical interest. On one hand, novel and innovative treatment strategies are needed to limit the infarct size, preserve left ventricular function and improve clinical outcomes in STEMI patients undergoing PPCI [ 2 , 10 , 18 , 33 – 35 ]. On the other hand, this multicentre study expands on the reported existence of potential differences in cardioprotection achieved with the most widely prescribed P2Y 12 receptor antagonists and demonstrates a benefit of ticagrelor over clopidogrel and prasugrel in clinical outcomes.…”

Improvements in pig agriculture through gene editing

“…In addition, the pig is intermediate between mice and primates in regard to immune responses and inflammation (Dawson et al 2017 , 2013 ; Starbaek et al 2018 ). Consequently, pigs are becoming more widely used as the large animal component of preclinical trials (Badimon et al 2019 ). With more gene edited (GE) pigs becoming available, swine have the potential to be a powerful tool for drug and device development (Boettcher et al 2021 ; Cozzi et al 2016 ; Donaldson et al 2021 ; Hering and O'Connell 2016 ).…”

Development and Long-Term Follow-Up of an Experimental Model of Myocardial Infarction in Rabbits

“…Cardiovascular disease, especially ischemic heart disease, is the leading cause of death nowadays [ 1 , 2 , 3 , 4 , 5 ], and global medium-term projections still consider ischemic heart disease as the most frequent [ 6 ]. Basic research and its transfer to the clinic are necessary to deepen the knowledge on the causes and mechanisms involved, as well as in the development and improvement of preventive, diagnostic, and therapeutic procedures to detect the disease in the preclinical stages, prevent its manifestations, and/or reduce the adverse effects [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ].…”