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Published on: June 3, 2018
IL-15: a novel prosurvival signaling pathway in cardiomyocytes
Yerem Yeghiazarians1, Norman Honbo, Isabella Imhof
1*Department of Medicine, University of California, San Francisco, San Francisco, CA; †Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA; ‡Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA; and §San Francisco Veterans Affairs Medical Center, University of California, San Francisco, San Francisco, CA.
Abstract:
Cardiovascular disease is the leading cause of death in Western countries. A major limitation of current treatments is the inability to efficiently repair or replace dead myocardium. Recently, stem cell-based therapies have been explored as an avenue to circumvent current therapeutic limitations. Overall, these therapies seem to result in small improvements in the contractile function of the heart. The exact mechanism(s) of action that underlie these improvements remain unknown, and it is believed that paracrine effects play a significant role. Previously, we had reported that an extract derived from bone marrow cells, in the absence of any live cell, contained cardioprotective soluble factors. In this study, we identify IL-15 as a putative cardioprotectant within the bone marrow cells paracrine profile. Using an in vitro culture system, we assessed the ability of IL-15 to protect cardiomyocytes under hypoxic conditions. For the first time, we have identified IL-15 receptors on the surface of cardiomyocytes and delineated the signaling system by which hypoxic cardiomyocytes may be protected from cellular death and rescued from oxidative stress with IL-15 treatment.
Insights
Interleukin-15 (IL-15) protects heart cells from death during oxygen deprivation. This discovery reveals a new signaling pathway for treating heart damage, offering hope for improved cardiovascular disease therapies.
Area of Science:
- Cardiology
- Cell Biology
- Immunology
Background:
- Cardiovascular disease is a primary cause of mortality in Western nations.
- Current treatments struggle to repair or replace damaged heart muscle (myocardium).
- Stem cell therapies show modest cardiac function improvements, likely via paracrine effects, but mechanisms are unclear.
Purpose of the Study:
- To identify cardioprotective soluble factors within bone marrow cell extracts.
- To investigate the role of Interleukin-15 (IL-15) in protecting cardiomyocytes.
- To elucidate the signaling pathway of IL-15 in hypoxic cardiomyocytes.
Main Methods:
- Utilized an in vitro culture system to test IL-15's protective effects on cardiomyocytes under hypoxic conditions.
- Identified IL-15 receptors on cardiomyocyte surfaces.
- Delineated the intracellular signaling cascade activated by IL-15.
Main Results:
- IL-15 demonstrated significant cardioprotective capabilities against hypoxia-induced cell death.
- IL-15 receptors were identified on cardiomyocytes, confirming direct interaction.
- The study mapped the signaling pathway through which IL-15 confers protection and reduces oxidative stress.
Conclusions:
- Interleukin-15 (IL-15) is a key cardioprotective factor secreted by bone marrow cells.
- IL-15 protects cardiomyocytes from hypoxic injury and oxidative stress via specific cell surface receptors.
- This finding opens new therapeutic avenues for cardiovascular disease by targeting the IL-15 signaling pathway.
