Exosomes for Intramyocardial Intercellular Communication
Elisabetta Cervio1, Lucio Barile1, Tiziano Moccetti1
1Molecular Cardiology Laboratory, Fondazione Cardiocentro Ticino, Via Tesserete, 6900 Lugano, Switzerland ; Swiss Institute of Regenerative Medicine (SIRM), Taverne, Switzerland.
Insights
Cardiomyocyte exosomes mediate intercellular communication in the heart, influencing gene expression in fibroblasts and endothelial cells. Cardiac progenitor cell-derived exosomes show therapeutic potential, reducing infarct size and improving cardiac function post-heart attack.
Area of Science:
- Cardiovascular Biology
- Cellular Communication
- Extracellular Vesicles
Background:
- Intercellular communication is vital for cardiac homeostasis and stress response.
- Cardiomyocytes (CMs) interact with endothelial cells (ECs) and fibroblasts.
- Exosomes are emerging as key mediators of these cellular messages.
Purpose of the Study:
- To investigate the role of exosomes in cardiac cell cross-talk.
- To explore the therapeutic potential of exosomes in heart disease.
Main Methods:
- Analysis of exosome content from cardiomyocytes, endothelial cells, cardiac fibroblasts, and cardiac progenitor cells (CPCs).
- Investigating the effects of cardiomyocyte-derived exosomes on fibroblasts and ECs.
- Evaluating the impact of CPC-derived exosomes in vivo models of myocardial infarction.
Main Results:
- Exosomes secreted by CMs, ECs, cardiac fibroblasts, and CPCs contain specific molecular cargo.
- CM-derived exosomes regulate gene expression in cardiac fibroblasts and ECs.
- CPC-derived exosomes protect CMs from apoptosis, promote angiogenesis, reduce infarct size, and improve cardiac function.
Conclusions:
- Exosomes are critical mediators of intercellular communication within the heart.
- Exosomes, particularly those from CPCs, hold significant therapeutic promise for treating heart disease.
Abstract:
Cross-talk between different cell types plays central roles both in cardiac homeostasis and in adaptive responses of the heart to stress. Cardiomyocytes (CMs) send biological messages to the other cell types present in the heart including endothelial cells (ECs) and fibroblasts. In turn, CMs receive messages from these cells. Recent evidence has now established that exosomes, nanosized secreted extracellular vesicles, are crucial mediators of such messages. CMs, ECs, cardiac fibroblasts, and cardiac progenitor cells (CPCs) release exosomes carrying nonrandom subsets of proteins, lipids, and nucleic acids present in their cells of origin. Exosomes secreted from CMs are internalized by fibroblasts and regulate gene expression in these cells as well as in ECs. CPC-derived exosomes protect CMs against apoptosis while also stimulating angiogenesis. They are rich in cardioprotective and proangiogenic microRNAs such as miR-146, miR-210, and miR-132. When injected into infracted hearts in vivo, CPC-derived exosomes reduce infarct size and improve cardiac function. Thus, exosomes are emerging both as key mediators of intercellular communication in the heart and as therapeutic candidates for heart disease.
