title: Age-related increase of stem marker expression influences vascular smooth muscle cell properties.
abstract: OBJECTIVE
  Aging represents a major risk factor for vascular disease development. With aging, changes of the biological properties of vascular smooth muscle cells (SMCs) are observed. Stem marker expression characterizes SMCs during developmental growth and atherosclerosis, but the contribution of SMCs with stem features to the age-related arterial remodeling remains largely unknown.
  
  
  RESULTS
  Immunostaining revealed rare vascular growth factor receptor-1(+) (flt-1(+)) and c-kit(+) cells in tunica media of grossly normal human young (17-30 years old) large arteries and 2-month old rat aorta, whereas CD133(+) cells were absent. In large arteries of human aged donors (64-77 years), flt-1(+) and c-kit(+) cell number increased in the intimal thickening and tunica media. Double immunofluorescence revealed that 30.6 ± 3% of flt-1(+) intimal cells co-expressed α-smooth muscle actin. Immunostaining, blots and RT-PCR documented the increased expression of flt-1 and c-kit in 20-24-month old rat aortic media. In vitro, old rat aortic SMCs proliferated and migrated more with greater flt-1, c-kit, NF-κB, VCAM-1, IAP-1 and MCP-1 levels and less α-smooth muscle actin and myosin compared to young SMCs. Old SMCs were also more susceptible to all-trans retinoic and NF-κB inhibition-induced apoptosis compared to young SMCs. Anti-flt-1 blocking antibody reduced migration and placental growth factor-induced but not serum and PDGF-BB-stimulated proliferation of old SMCs.
  
  
  CONCLUSIONS
  The increase of flt-1(+) and c-kit(+) SMCs characterizes large arteries of aged donors; the blocking of flt-1 signaling influences the behavior of old SMCs, suggesting that the accumulation of SMCs with a stem phenotype contributes to the age-dependent adverse arterial remodeling.
authors.affiliation: Anatomic Pathology Institute, Dept. of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Ferlosio
authors.forename: Gaetano
authors.initials: G
authors.lastname: Arcuri
authors.forename: Elena
authors.initials: E
authors.lastname: Doldo
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Scioli
authors.forename: Sandro
authors.initials: S
authors.lastname: De Falco
authors.forename: Luigi Giusto
authors.initials: LG
authors.lastname: Spagnoli
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D006801:Humans; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D017539:Tunica Intima / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D019009:Proto-Oncogene Proteins c-kit; D040281:Vascular Endothelial Growth Factor Receptor-1