Key result
Systemic injection of Substance-P significantly improved left ventricular ejection fraction (76.56% vs 59.3%) and reduced infarct size compared to saline in a rat model of cardiac ischemia-reperfusion injury.
Why the study?
Therapies using stem/progenitor cells are investigated to regenerate damaged hearts, and Substance-P mobilizes bone marrow stem cells and suppresses inflammation, but its role in tissue repair after ischemia-reperfusion injury compared with GCSF required investigation.
Does intravenous Substance-P improve cardiac function and reduce injury in rat models of cardiac ischemia-reperfusion injury compared to GCSF?
Does intravenous Substance-P improve cardiac function and reduce injury in rat models of cardiac ischemia-reperfusion injury compared to GCSF?
Absolute Event Rate: 76.56% vs 59.3%
p-value: p=<0.001
Substance-P may offer a superior therapeutic approach to GCSF for tissue repair and functional recovery following cardiac ischemia-reperfusion injury by modulating stem cell mobilization and early inflammation.
Substance-P may outperform GCSF in rat ischemia-reperfusion models; leaves open translation to human cardiac repair.
BACKGROUND/AIMS: Therapies using stem/progenitor cells have been experimentally and clinically investigated to regenerate damaged hearts. Substance-P (SP) induces bone marrow (BM) stem cell mobilization and suppresses inflammation in ischemic injuries. This study investigated the role of SP in BM stem cell mobilization and immune responses for tissue repair after ischemic-reperfusion injury (IRI), in comparison with that of granulocyte colony-stimulating factor (GCSF). METHODS: SP was intravenously injected into IRI rats and its affect was evaluated by determining colony forming efficiency, immune cell/ cytokine profiles, histological changes, and heart function through echocardiography. RESULTS: In the rat cardiac IRI model, SP suppressed IRI-mediated tumor necrosis factor-α induction, but increased the levels of interleukin-10, CD206+ monocytes, and regulatory T cells in the blood; reduced myocardial apoptosis at day 1 post-IRI; and markedly stimulated colony forming unit (CFU)-e and (CFU)-f cell mobilization. Efficacy of SP in the recovery of cardiac function after IRI was demonstrated by increased cardiac contractility, accompanied by reduced infarction sizes and fibrosis, and increased revascularization of vessels covered with alpha smooth muscle actin. These effects of SP were confirmed in an acute myocardial infarction (AMI) model. All effects mediated by SP were superior to those mediated by GCSF. CONCLUSION: Systemic injection of SP decreased early inflammatory responses and promoted stem cell mobilization, leading to a compact vasculature and improved cardiac function in cardiac IRI and AMI.
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Hong et al. (2019) studied Cardiac ischemia-reperfusion injury and acute myocardial infarction. Substance-P vs. Saline and GCSF was evaluated on Left ventricular ejection fraction (EF) at 1 week post-ischemia-reperfusion injury (p=<0.001). Systemic injection of Substance-P significantly improved left ventricular ejection fraction (76.56% vs 59.3%) and reduced infarct size compared to saline in a rat model of cardiac ischemia-reperfusion injury.
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