Effective intercellular communication is essential for cellular and tissue balance maintenance and response to challenges. Cellular communication methods involve direct cell contact or the release of biological molecules to cover short and long distances. However, a recent discovery in this communication network is the involvement of extracellular vesicles that host biological contents such as proteins, nucleic acids, and lipids, influencing neighboring cells. These extracellular vesicles are found in body fluids; thus, they are considered as potential disease biomarkers. Cardiovascular diseases are significant contributors to global morbidity and mortality, encompassing conditions such as ischemic heart disease, cardiomyopathies, electrical heart diseases, and heart failure. Recent studies reveal the release of extracellular vesicles by cardiovascular cells, influencing normal cardiac function and structure. However, under pathological conditions, extracellular vesicles composition changes, contributing to the development of cardiovascular diseases. Investigating the loading of molecular cargo in these extracellular vesicles is essential for understanding their role in disease development. This review consolidates the latest insights into the role of extracellular vesicles in diagnosis and prognosis of cardiovascular diseases, exploring the potential applications of extracellular vesicles in personalized therapies, shedding light on the evolving landscape of cardiovascular medicine.

Cardiovascular diseases are the leading cause of death worldwide, among which ischemic heart disease is the most representative. Myocardial infarction results from occlusion of a coronary artery, which leads to an insufficient blood supply to the myocardium. As it is well known, the massive loss of cardiomyocytes cannot be solved due the limited regenerative ability of the adult mammalian hearts. In contrast, some lower vertebrate species can regenerate the heart after an injury; their study has disclosed some of the involved cell types, molecular mechanisms and signaling pathways during the regenerative process. In this ‘two parts’ review, we discuss the current state-of-the-art of the main response to achieve heart regeneration, where several processes are involved and essential for cardiac regeneration.

Cardiovascular diseases are the leading cause of death worldwide, among which, ischemic heart disease is the most prevalent. Myocardial infarction results from occlusion of a coronary artery, which leads to an insufficient blood supply to the myocardium. As is well known, the massive loss of cardiomyocytes cannot be solved due the limited regenerative ability of the adult mammalian heart. In contrast, some lower vertebrate species can regenerate the heart after injury; their study has disclosed some of the involved cell types, molecular mechanisms and signaling pathways during the regenerative process. In this two-part review, we discuss the current state of the principal response in heart regeneration, where several involved processes are essential for full cardiac function in recovery.

The epicardium is an embryonic tissue layer essential for heart morphogenesis, providing progenitor cells and regulatory signals that support myocardial growth and coronary vessel formation. Epicardial cells arise from the proepicardium (PE) and spread over the myocardium to form the embryonic epicardium (EE), a transition that requires tight coordination between proliferation, migration, and lineage priming. However, the molecular mechanisms controlling this developmental timing remain incompletely understood. Here, we identify Trim71 as a key regulator of epicardial cell behaviour during the PE-to-EE transition. Trim71 is enriched in the PE and subsequently downregulated as cells acquire migratory competence. Functional analyses show that loss of Trim71 function decreases proliferation while promoting migration, as well as inducing the expression of epicardial commitment markers, suggesting that Trim71 is a controller of a progenitor-like state. We further demonstrate that Trim71 is necessary for these processes through a reciprocal feedback loop with the microRNAs let-7c and miR-30c. Our findings establish Trim71 as a temporal gatekeeper that coordinates the balance between progenitor maintenance and migration during early epicardial development. This Trim71-miRNAs axis constitutes a novel post-transcriptional layer of regulation that ensures the correct timing of epicardium development during cardiogenesis.