Brown Norway (BN) and BN Katholiek (BN/Ka) rat strains are both susceptible to develop lesions in the internal elastic lamina (IEL) of the aorta. BN/Ka rats are characterized by a single point mutation in the kininogen gene leading to deficiency in high- and low molecular weight kininogen. Recently, a suggestive quantitative trait locus for lesions in the IEL of the abdominal aorta was identified in an F2 intercross between Dahl-salt-sensitive (SS) and Brown Norway (BN) rats, implicating kininogen as a positional candidate gene. Therefore, BN and BN/Ka rat strains represent ideal model organisms to study the contribution of kininogen to the genetic predisposition to IEL formation, and to characterize the early events underlying vascular remodelling. Here we present data demonstrating that genetic kininogen deficiency promotes the formation of aneurysms in the abdominal aorta but not the development of atherosclerosis upon 12-week treatment with an atherogenic diet. Aneurysm formation was associated with an enhanced elastolysis, increased expression of MMP-2, MMP-3, down-regulation of TIMP-4, and with FasL- and caspase-3 mediated apoptosis. Kininogen deficient animals also featured changes in plasma cytokines compatible with apoptotic vascular damage, i.e. up-regulation of IFN-gamma and down-regulation of GM-CSF and IL-1beta. Finally, in response to atherogenic diet, kininogen deficient animals developed an increase in HDL/total cholesterol index, pronounced fatty liver and heart degeneration and lipid depositions in aortic media without atherosclerotic plaque formation. These findings suggest that genetic kininogen deficiency renders vascular tissue prone to aneurysmatic but not to atherosclerotic lesions.