Vascular injury response in mice is dependent on genetic background

Abstract

Mouse models are employed to unravel the pathophysiology of vascular restenosis. Although much effort has been spent on how to apply an adequate arterial injury, the influence of the genetic background of mice has not yet received sufficient consideration. The study presented herein was designed to demonstrate the influence of the mouse strain on vascular injury response. Mice of a defined background (50% 129 strain and 50% DBA strain) were backcrossed into either the 129 strain or the DBA strain. Male offspring were subjected to a femoral artery injury model by applying an electric current. Morphometric analysis revealed that backcrossing into the 129 strain resulted in a significant (P < 0.001) 17-fold increase in neointima formation (n = 17 mice) compared with backcrossing into the DBA strain (n = 19). The values of neointima area were 9.18 x 10(3) +/- 2.13 x 10(3) and 0.54 x 10(3) +/- 0.39 x 10(3) microm2, respectively. In conjunction, the vessel wall area was enhanced by 1.8-fold (P < 0.001). In contrast, no significant differences were found for the areas of the lumen and the tunica media. Similarly, a significant increase in neointima formation was also found for mice of pure 129 strain compared with pure DBA strain. The results underline the importance of the genetic background for studies on vascular injury response. Furthermore, because the mouse genome of the various strains is well defined, serial testing of the genetic background of mice will provide candidate genes and/or genetic modifiers controlling vascular injury response.

Disruption of SM22 Promotes Inflammation After Artery Injury via Nuclear Factor κB Activation

“…Since expression of pro-inflammatory genes is finely regulated during inflammation13, it is not surprising that changes in some pro-inflammatory genes such as Cxcl12 (sdf-1a) and Cx3cr1(a receptor for chemokine CX3CL1) were not detected under the same condition. In our system we only observed marginal neointima formation in injured carotids: this might be due to the C57Bl/6 based mixed genetic background that may be resistant to injury-induced neointima formation23. The dominant distribution of pro-inflammatory proteins in the VSMC-rich media suggests VSMCs as the cell sources for inflammation.…”

Genetic Susceptibility to Restenosis

“…As mentioned above, several surgical procedures have been reported for the induction of injury. [3][4][5] Tanaka et al 12 reported that contribution of bone marrow-derived cells to neointimal formation considerably differs depending on the procedures used for vascular injury induction; therefore, these procedures might influence the contribution of bone marrow-derived cells.…”

Genetic strain differences in platelet aggregation and thrombus formation of laboratory rats

“…While Wistar and Sprague-Dawley(SD)are commonlyused rat strainsfor thrombosis models, anumber of other strains have beenestablished.Each strain possessesgenetically unique characteristics suchash ypertension, hyperglycemia or hyperlipide-mia (11)(12)(13)(14).Itiswellknown that the genetic strain differences in miceand rats have impact on variousphysiological functions. It has been reported thatv ascular injuryr esponses,s uch as neointimal hyperplasia and compensatoryc ollateral artery growth after femoral artery occlusion, in mice arestrain-dependentand geneticallycontrolled (15)(16)(17)(18)(19).Also in rats,straindifferences in neointimalh yperplasia inducedb yballoon catheter injuryhavebeen reported (20). Tanase et al reported that significant strain differences in rat heartweightaffect cardiacenlargement and hypertrophy (21).…”