Abstract
The heart is a complex organ consisting of various cell types, each of which plays an important role in both physiological and pathophysiological conditions. The cells communicate with each other through direct cell-cell interactions and paracrine signaling, and both homotypic and heterotypic cell interactions contribute to the organized structure and proper function of the heart. Cardiomyocytes (CMs) and endothelial cells (ECs) are two of the most abundant cardiac cell types and they also play central roles in both cardiac remodeling and regeneration. The postnatal cell cycle withdrawal of CMs, which takes place within days or weeks after birth, represents the major barrier for regeneration in adult mammalian hearts, as adult CMs exhibit a very low proliferative capacity. Recent evidence highlights the importance of ECs not only as the most abundant cell type in the heart but also as key players in post-infarction remodeling and regeneration. In this MiniReview, we focus on blood vascular ECs and CMs and their roles and interactions in cardiac physiology and pathologies, with a special emphasis on cardiac regeneration. We summarize the known mediators of the bidirectional CM-EC interactions and discuss the related recent advances in the development of therapies aiming to promote heart repair and regeneration targeting these two cell types.
Highlights
THE MULTICELLULAR COMPOSITION OF THE HEARTThe heart is a complex multicellular organ with specialized structures and cells to take care of their own “subprojects.” Its main function, to maintain the blood circulation, depends on its pump function, making cardiomyocytes (CMs) the central cardiac cell type in both normal and pathological conditions
Recent evidence highlights the importance of endothelial cells (ECs) as the most abundant cell type in the heart and as key players in post-infarction remodeling and regeneration. In this MiniReview, we focus on blood vascular ECs and CMs and their roles and interactions in cardiac physiology and pathologies, with a special emphasis on cardiac regeneration
Cardiomyocytes produce and secrete proteins and peptides for paracrine signaling with other cardiac cells and for endocrine signaling with peripheral tissues
Summary
The heart is a complex multicellular organ with specialized structures and cells to take care of their own “subprojects.” Its main function, to maintain the blood circulation, depends on its pump function, making cardiomyocytes (CMs) the central cardiac cell type in both normal and pathological conditions. Cardiomyocytes are generally divided into pacemaker cells and forceproducing ventricular and atrial CMs. In order for the heart to function properly, additional cell types, such as blood and lymphatic endothelial cells (ECs), vascular smooth muscle cells (SMCs), fibroblasts, and pericytes are needed. They communicate with other cell types in the heart through both direct physical contacts and paracrine signaling (Figure 1) Pathological conditions, such as hypertension or myocardial infarction (MI), elicit maladaptive responses in both CMs and non-myocytes, contributing to the deterioration of cardiac function. The interactions between the two most abundant cell types, ECs, and CMs, have not been well characterized In this MiniReview we focus on the importance and mechanisms of communication between blood vascular ECs and CMs as well as their therapeutic implications in cardiac repair and regeneration
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