title: Platelet activation supports the development of venous thrombosis in hyperlipidemic rats.
abstract: This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cignarella
authors.forename: L
authors.initials: L
authors.lastname: Mussoni
authors.forename: L
authors.initials: L
authors.lastname: Mannucci
authors.forename: E
authors.initials: E
authors.lastname: Ferioli
authors.forename: L
authors.initials: L
authors.lastname: Puglisi
authors.forename: E
authors.initials: E
authors.lastname: Tremoli
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005342:Fibrinolysis; D006949:Hyperlipidemias / Q000097:blood*; D008297:Male; D015539:Platelet Activation; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D013924:Thrombophlebitis / Q000097:blood* / Q000209:etiology*; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D013929:Thromboxane B2