Development Of Atherosclerosis In Arteries Research Articles

Polymorphism of the C-509 gene of TGFB1 and the risk of obliterative atherosclerosis of lower limb arteries

Genetic factors play an important role in the development of obliterative atherosclerosis of arteries in the lower extremities. There are numerous data in the literature on polymorphic variants of the TGFB1 gene associated with the risk of development of cardiovascular diseases, but some of them are contradictory. The present study aimed at elucidating the role ofpolymorphism of509C/T genes of TGFB1 in the development of obliterative atherosclerosis in arteries of the lower extremities. The material included 328 samples of DNA from 203 unrelated subjects of Russian ethnicity residing in Central Russia (177 men and 23 women) with obliterative atherosclerosis of arteries in the lower extremities hospitalized to the Dpt. of Vascular Surgery and 125 age-matched controls. Genotyping of polymorphism of the C-509T (rs1800469) gene of TGFB1 was performed by the PCR-PDRF method with the use of oligonucleotide primers (Sintol Co., Moscow). The patients with obliterative atherosclerosis showed an increased frequency of the occurrence of alternative allele of the C-509T gene of TGFB1 in comparison with control subjects (r=0,0001). Simultaneously, the frequency of homozygous genotypes of wild-type alleles of -509CC decreased (OR=0,58, 95%CI=0,37-0,92, P=0,02) while the frequency of homozygotes with an alternative allele -509TT increased (OR=4,93, 95%CI=5,20-11,03, P=0,00004). The difference in the frequency of heterozygotes 509CT was absent (OR=0,81, 95%CI=0,52-1,27, P=0,35). Thus, polymorphism of the C-509T gene of TGFB1 is a significant predictor ofpredisposition to the development of obliterative atherosclerosis in arteries of the lower extremities.

WALL SHEAR STRESS IN A SUBJECT SPECIFIC HUMAN AORTA — INFLUENCE OF FLUID-STRUCTURE INTERACTION

Vascular wall shear stress (WSS) has been correlated to the development of atherosclerosis in arteries. As WSS depends on the blood flow dynamics, it is sensitive to pulsatile effects and local changes in geometry. The aim of this study is therefore to investigate if the effect of wall motion changes the WSS or if a rigid wall assumption is sufficient. Magnetic resonance imaging (MRI) was used to acquire subject specific geometry and flow rates in a human aorta, which were used as inputs in numerical models. Both rigid wall models and fluid-structure interaction (FSI) models were considered, and used to calculate the WSS on the aortic wall. A physiological range of different wall stiffnesses in the FSI simulations was used in order to investigate its effect on the flow dynamics. MRI measurements of velocity in the descending aorta were used as validation of the numerical models, and good agreement was achieved. It was found that the influence of wall motion was low on time-averaged WSS and oscillating shear index, but when regarding instantaneous WSS values the effect from the wall motion was clearly visible. Therefore, if instantaneous WSS is to be investigated, a FSI simulation should be considered.