Keywords: Cardiac Hypertrophy; Translational Research; Oligonucleotide-based drug; microRNAs

"MiR-199b and the hypertrophic heart: A journey across species"

The strategies to efficiently tackle cardiovascular diseases are still limited. The incomplete understanding of the mechanisms involved in heart disease and the poor translation of the preclinical findings into clinics emphasize the need to develop reliable and relevant research models. This thesis proposes a new aortic banding model in adult Vietnamese minipigs, promising increased reproducibility and decreasing surgery-associated mortality. It allows the study of the progression from an initial to an aggravated hypertrophic stage, and it is also a relevant platform to test new therapeutic approaches. As microRNAs have emerged as potential targets, this model was then used to perform pharmacological studies and assess the therapeutic potential of silencing miR-199b in diseased pigs using an RNA-based drug. Such treatment resulted in improved cardiac remodeling and function in adult minipigs. Moreover, this work emphasizes the differences between the two different ventricles during disease while unveiling possible therapeutic targets in both. The findings reported in this thesis constitute an advance in cardiovascular research, which could help boost heart failure diagnosis and therapy.

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Click here for the full dissertation.