title: Factor V Leiden mutation is associated with enhanced arterial thrombotic tendency in lean but not in obese mice.
abstract: The homozygous factor V Leiden mutation is associated with enhanced venous thrombotic risk. Obesity is a major risk factor for development of thrombotic cardiovascular disease. It was the objective of this study to investigate whether obesity affects the thrombotic risk associated with the mutation. Male mice with homozygous factor V Leiden mutation (Arg 504 to Gln) (FVQ/Q) and corresponding wild-type (WT) mice were kept on a standard fat diet (SFD) or high fat diet (HFD) for 14 weeks, and femoral artery thrombosis was induced by FeCl3 treatment. As compared to SFD, HFD feeding for 14 weeks resulted in significantly higher body weight and fat mass associated with adipocyte hypertrophy, which were, however, similar for both genotypes. In the FeCl3-induced arterial thrombosis model, FVQ/Q mice kept on SFD had a 40% shorter occlusion time (p = 0.015) and 40% lower blood flow (p = 0.03), as compared to WT mice. However, on HFD the occlusion time and blood flow were not significantly different for both genotypes. This finding could not be explained by differential changes of coagulation factors in either genotype fed on SFD or HFD. In conclusion, on SFD, but not on HFD, the factor V Leiden mutation is associated with enhanced thrombotic tendency after FeCl3 injury of the femoral artery, suggesting that in this model obesity rescues the increased thrombotic risk associated with the factor V Leiden mutation.
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N 1, Herestraat 49, Box 911, 3000 Leuven, Belgium.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nagai
authors.forename: H Roger
authors.initials: HR
authors.lastname: Lijnen
authors.forename: Audrey C A
authors.initials: AC
authors.lastname: Cleuren
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Berthe
authors.initials: B
authors.lastname: Van Hoef
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
authors.forename: Bart J M
authors.initials: BJ
authors.lastname: Van Vlijmen
mesh_terms: D000821:Animal Feed; D000818:Animals; D001158:Arteries / Q000473:pathology*; D001835:Body Weight; D002712:Chlorides; D005165:Factor V / Q000235:genetics*; D005290:Ferric Compounds / Q000494:pharmacology; D005838:Genotype; D006720:Homozygote; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009154:Mutation; D009765:Obesity / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics*
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D005165:Factor V; C024555:ferric chloride