Prof. José María Pérez Pomares

FIBROSTRATES; PID2021-122626-OB-I00

278.300 €

2022-2025

Fibrosis is a common fundamental pathophysiological feature of a large number of cardiac diseases (hypertensive, aging and diabetic heart; ischemic cardiomyopathy and myocardial infarction; dilated and arrhythmogenic cardiomyopathies; other less frequent conditions like Kawasaki disease). It is triggered by the loss of organ parenchymal cells, and characterized by the activation and proliferation (expansion) of fibroblasts. Cardiac fibroblasts (CF), which should be considered as the main cellular effectors of heart fibrosis, synthesize large amounts of extracellular matrix that deeply modify the histoarchitecture and functional properties of tissues. Moreover, fibrotic events also associate to inflammation, whose intensity may determine the duration of tissue remodeling processes, and even cause disease chronification.

Despite the evident biological and biomedical relevance, it is surprising that the CF still remains a largely under-researched cell type. In the last years, two fundamental concepts on CF have arisen: 1) the majority of CF form in the embryo from epicardial-derived mesenchymal progenitor-like cells and 2) the CF population is significantly heterogeneous, as it includes cells with different transcriptomic profiles. However, it is still unclear how the specific time point of embryonic EPDC generation and CF heterogeneity determine CF cell identity and functions in response to a dynamic extracellular environment. The general working hypothesis of this project is that the early embryonic origin of CF is pivotal to our understanding of the response of these cells to pathological stimuli. Such response implies the existence of: 1) homeostatic mechanisms regulating the general quiescence; 2) the low-pace differentiation of the relatively small numbers of fibroblasts contributing to the formation of the cardiac perimysium; 3) the existence of endogenous mechanisms that regulate the expansion of specific CF pools under pathological conditions. The scientific objectives of this project are to study these three aspects of fibrosis in the context of three different cardiac disease animal models.

National Research Agency (EAI) – Spanish Ministry of Science and Innovation