title: High-density lipoprotein cholesterol regulates endothelial progenitor cells by increasing eNOS and preventing apoptosis.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) are implicated as an important marker of endothelial function and cardiovascular risk. In the present study, we examined whether high-density lipoprotein (HDL) cholesterol plays a role in the peripheral EPC levels and its underlying mechanisms in the HDL cholesterol-induced elevation of EPCs.
  
  
  METHODS
  For the clinical study, vascular risk factors and blood markers were measured and EPC colony forming units were counted after 7 days of culture. For the in vitro study, after 7 days of culture, EPCs were incubated in the presence or absence of HDL for 24h followed by measurements of eNOS and pro-MMP-9 expression and caspase-3 activity.
  
  
  RESULTS
  EPC colony levels significantly correlated with HDL levels (P=0.017). HDL treatment significantly increased eNOS protein expression in EPCs (P<0.001) while it significantly decreased pro-MMP-9 levels at the concentration of 50 microg/mL (P=0.002). Homocysteine treatment significantly increased caspase-3 activity whereas HDL significantly decreased it as compared to the homocysteine-only treated group.
  
  
  CONCLUSIONS
  The data demonstrate that EPC colony levels are significantly lower in individuals with low HDL and that HDL increases eNOS and decreases pro-MMP-9 in EPCs. HDL also prevents EPC apoptosis through inhibition of caspase-3 activity suggesting a possible mechanism for its positive effects on circulating EPC numbers.
authors.affiliation: Department of Medicine, Division of Neurology, Endothelial Progenitor Cell Laboratory, 771 HMRC, University of Alberta, Edmonton, Alta. T6G 2S2, Canada.
authors.forename: Raza
authors.initials: R
authors.lastname: Noor
authors.forename: Umar
authors.initials: U
authors.lastname: Shuaib
authors.forename: Chen Xu
authors.initials: CX
authors.lastname: Wang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Todd
authors.forename: Usman
authors.initials: U
authors.lastname: Ghani
authors.forename: Brenda
authors.initials: B
authors.lastname: Schwindt
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism*; D018929:Cell Culture Techniques; D008076:Cholesterol, HDL / Q000097:blood / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D008076:Cholesterol, HDL; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D012697:Serine Endopeptidases; C463979:pro-MMP-9 activator; D053148:Caspase 3