Experimental Models to Study Endothelial to Mesenchymal Transition in Myocardial Fibrosis and Cardiovascular Diseases

Abstract

Fibrosis is a common feature of cardiovascular diseases and targets multiple organs, such as the heart and vessels. Endothelial to mesenchymal transition is a complex, vital process that occurs during embryonic formation and plays a crucial role in cardiac development. It is also a fundamental process implicated in cardiac fibrosis and repair, but also in other organs. Indeed, in numerous cardiovascular diseases, the endothelial-to-mesenchymal transition has been shown to be involved in the generation of fibroblasts that are able to produce extracellular matrix proteins such as type I collagen. This massive deposition results in tissue stiffening and organ dysfunction. To advance our understanding of this process for the development of new specific diagnostic and therapeutic strategies, it is essential to develop relevant cellular and animal models of this process. In this review, our aim was to gain an in-depth insight into existing in vitro and in vivo models of endothelial to mesenchymal transition in cardiovascular diseases with a focus on cardiac fibrosis. We discuss important parameters impacting endothelial to mesenchymal transition, and we give perspectives for the development of relevant models to decipher the underlying mechanisms and ultimately find new treatments specific to fibrosis happening in cardiovascular diseases.

Keywords: animal models; cardiovascular disease; endothelial to mesenchymal transition; fibrosis; in vitro models.

Figure 1

Overview of pathways targeted for the study of EndMT in cardiovascular diseases. (A) Endothelial to mesenchymal transition process. (B) Pathways targeted in in vitro models for the study of EndMT. Parts of the figure were drawn by using pictures from Servier Medical Art.

Figure 2

Existing in vivo models for the study of EndMT in cardiovascular diseases. (A) Principle for the generation of constitutive Cre animal models. (B) Principle for the generation of inducible Cre animal models. (C) Principle for the generation of dual recombinase animal models (upper panel) and its application in the study of EndMT (lower panel). Parts of the figure were drawn by using pictures from Servier Medical Art.

Figure 2

Existing in vivo models for the study of EndMT in cardiovascular diseases. (A) Principle for the generation of constitutive Cre animal models. (B) Principle for the generation of inducible Cre animal models. (C) Principle for the generation of dual recombinase animal models (upper panel) and its application in the study of EndMT (lower panel). Parts of the figure were drawn by using pictures from Servier Medical Art.