Mouse chromosome 17 candidate modifier genes for thrombosis.

Two overlapping quantitative trait loci (QTLs) for clot stability, Hmtb8 and Hmtb9, were identified on mouse chromosome 17 in an F2 intercross derived from C57BL/6J (B6) and B6-Chr17(A/J) (B6-Chr17) mouse strains. The intervals were in synteny with a QTL for thrombotic susceptibility on chromosome 18 in a human study, and there were 23 homologs between mouse and human. The objective of this study was to determine whether any of these genes in the syntenic region are likely candidates as modifiers for clot stability.

A physiological function for apolipoprotein(a): a natural regulator of the inflammatory response.

Structural similarities between apolipoprotein(a) (apo(a)), the unique apoprotein of lipoprotein(a), and plasminogen, the zymogen of plasmin, can interfere with functions of plasmin (ogen) in vitro. The purpose of this study was to evaluate the role of apo(a) in inflammation in vivo using apo(a) transgenic mice and to determine if effects are plasminogen-dependent using backgrounds that are either plasminogen-replete or plasminogen-deficient. After administration of peritoneal inflammatory stimuli, thioglycollate, bioimplants or lipopolysaccharide, the number of responding peritoneal neutrophils and macrophages were quantified.

Quantitative trait locus analysis for hemostasis and thrombosis.

Susceptibility to thrombosis varies in human populations as well as many in inbred mouse strains. The objective of this study was to characterize the genetic control of thrombotic risk on three chromosomes. Previously, utilizing a tail-bleeding/rebleeding assay as a surrogate of hemostasis and thrombosis function, three mouse chromosome substitution strains (CSS) (B6-Chr5(A/J), Chr11(A/J), Chr17(A/J)) were identified (Hmtb1, Hmtb2, Hmtb3).

Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice.

Inflammation plays a critical role in the development of cardiovascular diseases. Infiltration of leukocytes to sites of injury requires their exit from the blood and migration across basement membrane; this process has been postulated to require remodeling of the ECM. Plasminogen (Plg) is a protease that binds to the ECM and, upon conversion to plasmin, degrades multiple ECM proteins.

Genetic background determines response to hemostasis and thrombosis.

Background: Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis.