Effects of G-CSF on left ventricular remodeling and heart failure after acute myocardial infarction

Abstract

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophil progenitors. G-CSF also possesses immunomodulatory properties. G-CSF-induced hematopoietic stem cell mobilization is widely used clinically for transplantation. After it was recently reported that G-CSF mobilizes bone marrow stem cells (BMSCs) into the infarcted hearts and accelerates the differentiation into vascular cells and cardiac myocytes, myocardial regeneration utilizing mobilization of BMSCs by G-CSF is attracting the attention of investigators. In animal models, G-CSF prevents left ventricular remodeling and dysfunction after acute myocardial infarction, at least in part, through a decrease in apoptotic cells and an increase in vascular cells. Although it is controversial whether BMSCs mobilized by G-CSF can differentiate into cardiac myocytes, G-CSF-induced angiogenesis is indeed recognized in infarcted heart. The cardioprotective effects of G-CSF are recognized even in isolated perfused heart. In addition, G-CSF activates various signaling pathways such as Akt, extracellular signal-regulated kinase, and Janus kinase 2/signal transducer and activator of transcription 3 through G-CSF receptors in cardiac myocytes. These observations suggest that G-CSF not only induces mobilization of stem cells and progenitor cells but also acts directly on cardiomyocytes. Therefore, G-CSF may be utilized as a novel agent to have protective and regenerative effects on injured myocardium. Although the effects of G-CSF on the progression of atherosclerosis are still unclear, there is a possibility that G-CSF will become a promising therapy for ischemic heart diseases.

Granulocyte colony-stimulating factor impairs liver regeneration in mice through the up-regulation of interleukin-1β

“…G-CSF-induced hematopoietic stem cell mobilization has been widely used for transplantation. Many studies have reported that G-CSF mobilizes BM stem cells into infarcted cardiac tissue and accelerates their differentiation into vascular cells and cardiac myocytes [18]. The role of G-CSF has also been investigated in such inflammatory bowel diseases as Crohn's disease and ulcerative colitis [19].…”

Granulocyte Colony Stimulating Factor Prevents Kidney Infarction and Attenuates Renovascular Hypertension

“…G-CSF exerts reparative and regenerative effects in various ischemic tissues, including heart [3,5], brain [6] and kidney [7]. Additionally, pretreatment with G-CSF attenuates renal ischemia/ reperfusion injury, and this cytoprotection seems to be associated with its anti-apoptotic action [8].…”

Mobilization of Bone Marrow Cells by CSF3 Protects Mice from Bleomycin-Induced Lung Injury

“…For example, recombinant human CSF3 mobilized bone marrow stem cells to damaged brain tissue, induced the release of a neurotrophic factor and reduced brain tissue damage [43,44]. In addition, CSF3 mobilized bone marrow stem cells to myocardial infarction sites and promoted cardiac myocyte repair [35,45]. …”