Cardiac telocytes inhibit cardiac microvascular endothelial cell apoptosis through exosomal miRNA-21-5p-targeted cdip1 silencing to improve angiogenesis following myocardial infarction

Abstract

Promotion of cardiac angiogenesis in ischemic myocardium is a critical strategy for repairing and regenerating the myocardium after myocardial infarction (MI). Currently, effective methods to aid in the survival of endothelial cells, to avoid apoptosis in ischemic myocardium and to achieve long-term cardiac angiogenesis are still being pursued. Here, we investigated whether cardiac telocyte (CT)-endothelial cell communication suppresses apoptosis and promotes the survival of endothelial cells to facilitate cardiac angiogenesis during MI. Methods: CT exosomes were isolated from CT conditioned medium, and their miRNA profile was characterized by small RNA sequencing. A rat model of left anterior descending coronary artery ligation (LAD)-mediated MI was assessed with histology for infarct size and fibrosis, immunostaining for angiogenesis and cell apoptosis and echocardiography to evaluate the therapeutic effects. Cardiac microvascular endothelial cells (CMECs) and the LAD-MI model treated with CT exosomes or CT exosomal miRNA-21-5p in vitro and in vivo were assessed with cellular and molecular techniques to demonstrate the underlying mechanism. Results: CTs exert therapeutic effects on MI via the potent paracrine effects of CT exosomes to facilitate the inhibition of apoptosis and survival of CMECs and promote cardiac angiogenesis. A novel mechanism of CTs is revealed, in which CT-endothelial cell communication suppresses apoptosis and promotes the survival of endothelial cells in the pathophysiological myocardium. CT exosomal miRNA-21-5p targeted and silenced the cell death inducing p53 target 1 ( Cdip1 ) gene and thus down-regulated the activated caspase-3, which then inhibited the apoptosis of recipient endothelial cells under ischemic and hypoxic conditions, facilitating angiogenesis and regeneration following MI. Conclusions: The present study is the first to show that CTs inhibit cardiac microvascular endothelial cell apoptosis through exosomal miRNA-21-5p-targeted Cdip1 silencing to improve angiogenesis in myocardial infarction. It is believed that these novel findings and the discovery of cellular and molecular mechanisms will provide new opportunities to tailor novel cardiac cell therapies and cell-free therapies for the functional and structural regeneration of the injured myocardium.

A Bibliometric Analysis of Exosomes in Cardiovascular Diseases From 2001 to 2021

“…From 2007 to 2010, small numbers of articles began to appear; however the research during this period was embryonic. From 2010 to 2016, the number of articles began to increase, and a growing number of investigators began to pay attention to the role of exosomes in cardiovascular science (40)(41)(42)(43)(44)(45). In the past 5 years, the number of published articles grew rapidly, suggesting that the research of exosomes is becoming more mature and its research in cardiovascular science is likely to become a hot topic and research direction in the future.…”

Telocytes and their structural relationships with surrounding cell types in the skin of silky fowl by immunohistochemistrical, transmission electron microscopical and morphometric analysis

“…TCs play a role in regulating the local microenvironment by cell-to-cell contacts and extracellular shedding vesicles ( Díaz-Flores et al., 2020 ). A recent study confirmed that TCs inhibit microvascular endothelial cell apoptosis through exosomal miRNA to improve angiogenesis ( Liao et al., 2021 ). It is suggested that TCs participate in the repair of injury through their exosomes.…”

Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation

“…In recent years, TCs are known to produce interleukins IL-6, IL-2, IL-10, IL-13, VEGF, macrophage inflammatory proteins 1a (MIP-1a), MIP-2 and MCP-1 63 , angiogenic microRNAs 38 . For example, through exosomal miRNA-21-5p, cardiac TCs ensure the survival of microvascular endothelial cells in myocardial infarction 64 .…”