title: Circulating and vein wall P-selectin promote venous thrombogenesis during aging in a rodent model.
abstract: BACKGROUND
  The objective of this study was to identify the direct relationship between aging and selectin activation during acute venous thrombosis in mice of varying ages. We hypothesized that older animals would have increased venous thrombus formation as a result of age associated-increases of pro-inflammatory molecules within the vein wall when compared to younger animals.
  
  
  METHODS
  Deep venous thrombosis (DVT) was induced in 4 and 18month old C57BL/6 mice using the electrolytic inferior vena cava model (EIM) of DVT. Blood and tissue samples were collected at baseline (TC), 6hours, and 2days post-thrombosis induction.
  
  
  RESULTS
  Older mice had significantly larger thrombi versus younger mice at 6H (18.4±6.21 vs. 13.0±4.29×10(-3) grams, p=0.0033) and 2D (18.4±4.27 vs. 13.0±5.01×10(-3) grams, p=0.0005), higher soluble P-selectin levels at 6H (13±2.5 vs. 8.4±2.7ng/mg p=0.0010) and 2D (12.7±5.0 vs. 5.9±1.3ng/mg p=0.0020), and higher vein wall P-selectin levels at 6H (1.94×10(5)±3.56×10(4) vs. 4.81±2.29×10(4) pg/mg p=0.0001) and 2D (1.38×10(5)±5.65×10(4) vs. 3.73±1.66×10(4) pg/mg p=0.0177). Older animals also had significantly higher platelet numbers at 6H (841±203.8 vs. 564±164.8K/μL p=0.0001), and 2D (1002±342.9 vs. 690±186.1K/μL p=0.0003), with corresponding increases in mean platelet volume versus younger mice post thrombosis (p≤0.01).
  
  
  CONCLUSIONS
  Older animals had significantly larger venous thrombi versus younger animals post-thombosis, as a result of high levels of P-selectin both in the circulation and locally at the level of the vein wall. Expression of local and soluble P-selectin increased with age, resulting in a pro-thrombotic environment not represented in younger mice.
authors.affiliation: Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, Michigan, United States. Dorian.Culmer@pfizer.com
authors.forename: Dorian Laird
authors.initials: DL
authors.lastname: Culmer
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Diaz
authors.forename: Angela Eileen
authors.initials: AE
authors.lastname: Hawley
authors.forename: Tatum Olivia
authors.initials: TO
authors.lastname: Jackson
authors.forename: Katherine Anne
authors.initials: KA
authors.lastname: Shuster
authors.forename: Robert Edwin
authors.initials: RE
authors.lastname: Sigler
authors.forename: Thomas William
authors.initials: TW
authors.lastname: Wakefield
authors.forename: Daniel Durant
authors.initials: DD
authors.lastname: Myers
mesh_terms: D000367:Age Factors; D000818:Animals; D001777:Blood Coagulation; D004195:Disease Models, Animal; D019040:E-Selectin / Q000097:blood; D007249:Inflammation / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000097:blood* / Q000235:genetics; D010976:Platelet Count; D013997:Time Factors; D015854:Up-Regulation; D014682:Vena Cava, Inferior / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D019040:E-Selectin; D018836:Inflammation Mediators; D019007:P-Selectin