Cholesterol and Hematopoietic Stem Cells: Inflammatory Mediators of Atherosclerosis

• Published in: Stem cells translational medicine Vol. 3; no. 5; pp. 549 - 552
• Main Authors: Lang, Jennifer K., Cimato, Thomas R.
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01.05.2014; Oxford University Press
• Subjects: Acute coronary syndromes; Animals; Antagonism; Arteriosclerosis; Atherosclerosis; Atherosclerosis - blood; Atherosclerosis - pathology; Bone marrow; Cardiovascular disease; Cholesterol; Cholesterol - blood; Coronary vessels; Cytokines - blood; Heart attacks; Hematopoietic stem cells; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - pathology; Human subjects; Humans; Inflammation; Inflammation Mediators - blood; Investigations; Low density lipoprotein; Mice; Monocytes - metabolism; Monocytes - pathology; Neutrophils; Neutrophils - metabolism; Neutrophils - pathology; Prevention; Spleen; Stem cell transplantation; Stem cells; Stroke
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2013-0205

Recent findings have provided new insight into the interaction among hematopoietic stem cells (HSPCs), cholesterol, and atherosclerosis. The authors review studies in mice and consider the connection in humans between cholesterol and HSPCs. Recent studies represent an important avenue to determine whether the biology of humans is the same and whether antagonism of HSPC mobilization and differentiation in response to cholesterol is of benefit for prevention and regression of atherosclerosis. Summary Atherosclerosis causing heart attack and stroke is the leading cause of death in the modern world. Therapy for end‐stage atherosclerotic disease using CD34+ hematopoietic cells has shown promise in human clinical trials, and the in vivo function of hematopoietic and progenitor cells in atherogenesis is becoming apparent. Inflammation plays a central role in the pathogenesis of atherosclerosis. Cholesterol is a modifiable risk factor in atherosclerosis, but in many patients cholesterol levels are only mildly elevated. Those with high cholesterol levels often have elevated circulating monocyte and neutrophil counts. How cholesterol affects inflammatory cell levels was not well understood. Recent findings have provided new insight into the interaction among hematopoietic stem cells, cholesterol, and atherosclerosis. In mice, high cholesterol levels or inactivation of cholesterol efflux transporters have multiple effects on hematopoietic stem cells (HSPCs), including promoting their mobilization into the bloodstream, increasing proliferation, and differentiating HSPCs to the inflammatory monocytes and neutrophils that participate in atherosclerosis. Increased levels of interleukin‐23 (IL‐23) stimulate IL‐17 production, resulting in granulocyte colony‐stimulating factor (G‐CSF) secretion, which subsequently leads to HSPC release into the bloodstream. Collectively, these findings clearly link elevated cholesterol levels to increased circulating HSPC levels and differentiation to inflammatory cells that participate in atherosclerosis. Seminal questions remain to be answered to understand how cholesterol affects HSPC‐mobilizing cytokines and the role they play in atherosclerosis. Translation of findings in animal models to human subjects may include HSPCs as new targets for therapy to prevent or regress atherosclerosis in patients