PMID- 24646491
OWN - NLM
STAT- MEDLINE
DCOM- 20140721
LR  - 20211021
IS  - 2157-6564 (Print)
IS  - 2157-6580 (Electronic)
IS  - 2157-6564 (Linking)
VI  - 3
IP  - 5
DP  - 2014 May
TI  - Cholesterol and hematopoietic stem cells: inflammatory mediators of 
      atherosclerosis.
PG  - 549-52
LID - 10.5966/sctm.2013-0205 [doi]
AB  - 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.
FAU - Lang, Jennifer K
AU  - Lang JK
AD  - Clinical and Translational Research Center, Department of Medicine/Cardiology, 
      School of Medicine and Biomedical Sciences, State University of New York at 
      Buffalo, Buffalo, New York, USA.
FAU - Cimato, Thomas R
AU  - Cimato TR
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140319
PL  - England
TA  - Stem Cells Transl Med
JT  - Stem cells translational medicine
JID - 101578022
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*blood/pathology
MH  - Cholesterol/blood
MH  - Cytokines/blood
MH  - Hematopoietic Stem Cells/*metabolism/pathology
MH  - Humans
MH  - Inflammation Mediators/*blood
MH  - Mice
MH  - Monocytes/metabolism/pathology
MH  - Neutrophils/metabolism/pathology
PMC - PMC4006493
EDAT- 2014/03/22 06:00
MHDA- 2014/07/22 06:00
PMCR- 2015/05/01
CRDT- 2014/03/21 06:00
PHST- 2014/03/21 06:00 [entrez]
PHST- 2014/03/22 06:00 [pubmed]
PHST- 2014/07/22 06:00 [medline]
PHST- 2015/05/01 00:00 [pmc-release]
AID - sctm.2013-0205 [pii]
AID - 20130205 [pii]
AID - 10.5966/sctm.2013-0205 [doi]
PST - ppublish
SO  - Stem Cells Transl Med. 2014 May;3(5):549-52. doi: 10.5966/sctm.2013-0205. Epub 
      2014 Mar 19.