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Neonatal regeneration after myocardial infarction: Do fibroblasts have a role?
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Orientador(es)
Resumo(s)
The limited regenerative capacity of the adult mammalian heart is a contributing factor to the high rates of morbidity and mortality reported for cardiovascular disease. One of the most lethal subsets of cardiovascular diseases is myocardial infarction (MI) that occurs following a blockage of blood flow in the coronary artery, leading to myocardial loss by ischaemia. In 2011, it was first reported that 1-day-old mice (P1) hearts can regenerate after injury by activating the proliferation of pre-existing cardiomyocytes. This regenerative potential is progressively lost in the first week of life, as 7-day-old mice (P7) fail to regenerate their myocardium and develop significant fibrosis. Cardiac fibroblasts are a dynamic cell type known to be involved in the repair process, having important roles in all phases of cardiac injury - inflammation, proliferation, and remodelling. More recent evidence have shown that neonatal fibroblasts and fibroblasts-secreted factors may also support cardiac regeneration. Studies characterizing in detail the regenerative response are scarce, especially in what concerns the role of cardiac fibroblasts, which are main mediators of the repair process in the adult heart. Herein, to unveil how these cells may regulate the neonatal cardiac regenerative process we established a protocol to induce MI in 1‐day‐old mice using the left anterior descending artery ligation model and performed a long term functional and histological evaluation of the neonatal heart after MI. Compensatory cellular and functional responses to MI detected in the first month of life are transient and are fully resolved 90 days after injury. We also report a rapid immune cell and fibroblast response to MI, concentrated in the first 5 days after injury, concomitant with cardiomyocyte proliferation 7 days after injury. Furthermore, extracellular matrix remodelling coincides with the recruitment and proliferation of neonatal cardiac fibroblasts in the injury site, thus reinforcing the direct involvement of cardiac fibroblasts in cardiovascular regeneration.
Descrição
Tese de mestrado, Biologia Evolutiva e do Desenvolvimento, Universidade de Lisboa, Faculdade de Ciências, 2021
Palavras-chave
Enfarte do miocárdio Fibroblastos cardíacos Regeneração Doenças cardiovasculares Proliferação de cardiomiócitos Teses de mestrado - 2021