Activation of stem cell up-regulation/mobilization: a cardiovascular risk in both mice and humans with implications for liver disease, psoriasis and SLE

Abstract

John M Gemery,1,2 Andrew R Forauer,1,2 Eric K Hoffer1,2 1Geisel School of Medicine, Dartmouth, Hanover, NH 03755, USA; 2Dartmouth-Hitchcock Medical Center, Department of Radiology, Division of Interventional Radiology, One Medical Center Drive, Lebanon, NH 03756, USAAbstract: Experimentally induced injury triggers up-regulation and mobilization of stem cells in Apoe -/- mice that causes accelerated atherosclerosis. Abca1 -/- Abcg1-/- mice have chronic activation of stem cell up-regulation/mobilization and accelerated atherosclerosis. In addition, the Abca1 -/- Abcg1-/- mice have elevation of serum cytokines G-CSF, IL-17 and IL-23, each necessary for stem cell mobilization. IL-17 and IL-23 are elevated in two human illnesses that have cardiovascular (CV) risk independent of traditional risk factors—SLE and psoriasis. Serum G-CSF, which can be elevated in liver disease, predicts major adverse cardiovascular events in humans. These serum cytokine elevations suggest activation of the stem cell mobilization mechanism in humans that results, as in mice, in accelerated atherosclerosis. Efforts to reduce CV disease in these patient populations should include mitigation of the diseases that trigger stem cell mobilization. Since activation of the stem cell up-regulation/mobilization mechanism appears to accelerate human atherosclerosis, use of stem cells as therapy for arterial occlusive disease should distinguish between direct administration of stem cells and activation of the stem cell up-regulation/mobilization mechanism.Keywords: stem cells, HDL, vascular disease, SLE, psoriasis, liver disease

Keywords

• Stem cells
• HDL
• vascular disease
• SLE
• psoriasis
• liver disease