The Toll-like receptor 4 gene expression level and single nucleotide variants in the development of atherosclerosis

   Atherosclerosis is considered as a chronic inflammatory disease characterized by dysfunction of the endothelium of the vascular wall, migration of immune cells, subendothelial accumulation of lipids and proliferation of vascular smooth muscle cells with further formation of atherosclerotic plaques. Research data suggests the potential importance of Toll-like receptors (TLRs) and other key components of the innate immune system in the pathologies associated with atherosclerosis. Toll-like receptor 4 (TLR4) may play a key role in the immunopathogenesis of atherosclerosis.

   The aim of this study was to explore the association of TLR4 gene expression in macrophages and polymorphic variants rs4986790 and rs4986791 with the development of atherosclerosis in the St. Petersburg population.

   The study included 671 individuals: 220 patients with atherosclerosis of various localizations (coronary, cerebral, lower extremity artery pool); 75 patients with familial hypercholesterolemia with/without manifestation of atherosclerosis; 376 individuals without cardiovascular pathology as the control group. Genotyping of polymorphic variants of the TLR4 gene was performed by PCR followed by restriction analysis. Analysis of the TLR4 gene expression level in was performed in differentiated in vitro macrophages of 13 patients with coronary atherosclerosis and 19 representatives of the control group by real-time PCR. Patients with coronary atherosclerosis were characterized by an increased level of TLR4 gene expression in macrophages when compared with the control group. The Asp299Gly and Thr399Ile variants of the TLR4 gene were not associated with atherosclerosis development in the population of St. Petersburg, including patients with familial hypercholesterolemia.

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