CD73‐derived adenosine and tenascin‐C control cytokine production by epicardium‐derived cells formed after myocardial infarction

Abstract

Epicardium-derived cells (EPDCs) play a fundamental role in embryonic cardiac development and are reactivated in the adult heart in response to myocardial infarction (MI). In this study, EPDCs from post-MI rat hearts highly expressed the ectoenzyme CD73 and secreted the profibrotic matricellular protein tenascin-C (TNC). CD73 on EPDCs extensively generated adenosine from both extracellular ATP and NAD. This in turn stimulated the release of additional nucleotides from a Brefeldin A-sensitive intracellular pool adenosine-AR signaling, forming a positive-feedback loop. AR activation, in addition, strongly promoted the release of major regulatory cytokines, such as IL-6, IL-11, and VEGF. TNC was found to stimulate EPDC migration and, together with ATP-P2XR signaling, to activate inflammasomes in EPDCs TLR4. Our results demonstrate that EPDCs are an important source of various proinflammatory factors in the post-MI heart controlled by purinergic and TNC signaling.-Hesse, J., Leberling, S., Boden, E., Friebe, D., Schmidt, T., Ding, Z., Dieterich, P., Deussen, A., Roderigo, C., Rose, C. R., Floss, D. M., Scheller, J., Schrader, J. CD73-derived adenosine and tenascin-C control cytokine production by epicardium-derived cells formed after myocardial infarction.

P2X7 receptor in cardiovascular disease: The heart side

“…These cells can release IL‐1β and IL‐6 upon stimulation with LPS and ATP or BzATP. This effect is abolished after treatment with the P2X7 antagonist A740003 . The P2X7 expression on the heart was confirmed in different studies.…”

“…133 This effect is abolished after treatment with the P2X7 antagonist A740003. 134 The P2X7 expression on the heart was confirmed in different studies. In the sinoatrial node and atria of the adult heart, the presence of the P2X7 receptor has already been detected through immunohistochemistry, qPCR and in situ hybridization.…”

CD73 positive adipose derived mesenchymal stem cells enhance cardiac repair with experimental myocardial infarction by promoting angiogenesis

“…Inhibition of CD73 with anti-CD73 antibodies or APCP reduced tumor angiogenesis in mice [30]. The mechenism is probably related to CD73's interaction with adenosine receptor A2B [31]. This interaction will stimulates vascular smooth muscle cells, endothelial cells, immune cells and tumor cells to secrete VEGF.…”

Overproduction of Tenascin‐C Driven by Lipid Accumulation in the Liver Aggravates Hepatic Ischemia/Reperfusion Injury in Steatotic Mice

“…Notably, Tnc is rapidly induced in adult tissues in response to pathological stress . Although Tnc is necessary for physiological tissue repair, its misregulated expression has been associated with a variety of pathological conditions, which include rheumatoid arthritis, cancer, myocardial infarction, hepatitis, and hepatic IRI . Tnc is a pleiotropic molecule implicated in various cellular functions, with regulation of cell adhesion and migration being among the most characterized .…”

“…(16) Although Tnc is necessary for physiological tissue repair, its misregulated expression has been associated with a variety of pathological conditions, which include rheumatoid arthritis, cancer, myocardial infarction, hepatitis, and hepatic IRI. (17)(18)(19)(20)(21)(22) Tnc is a pleiotropic molecule implicated in various cellular functions, with regulation of cell adhesion and migration being among the most characterized. (18) Growing evidence now points to Tnc as a key regulator of both innate and adaptive immunity.…”