P215Tissue expression of angiotensin 2 receptor type 1 in patients with significant atherosclerosis

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Purpose: The current study was designed to examine local renin-angiotensin system (RAS) activity on the basis of estimation of expression level of angiotensin II receptor type 1 (AT1R) in smooth muscle cells (SMCs) in intact and affected with atherosclerosis arteries in patients with significant atherosclerosis.

Methods: We investigated 31 resected medium caliber arteries. 17 arteries of patients with low extremity atherosclerosis collected during vascular reconstructive operations made the first study group. The second group consisted of 14 intact mammary arteries collected during coronary bypass in subjects with multivessel coronary disease. The groups did not differ significantly by age, gender, arterial hypertension severity, concomitant disorders. AT1R localized in SMCs were detected by immunohistochemistry with specific polyclonal antibodies to AT1R. Staining intensity of angiotensin II receptors in muscular layer of arteries was assessed semiquantitatively by percentage of positive cells according to 3-level scale: ≪-≫, negative; ≪+≫, focal or week expression; ≪++≫, diffuse or strong positive reaction.

Results: Similar results were achieves in both groups. In 8 arteries of the first group (47.05%) the low expression (+) of AT1R was found, in other 8 arteries the AT1R expression (47.05%) was strong. There was no AT1R expression (-) in 1 case (5.9%). Thus, significant tissue expression was observed approximately in 50% of patients with atherosclerotic arteries, moreover it did not depend on the studied vascular bed (affected or intact).

Conclusions: The study results suggest that the tissue RAS activity increases inhomogeneously among patients with artery atherosclerosis. AT1R expression levels in intact arteries does not differ of those in atherosclerotic arteries (p>0.05). AT1R expression in SMCs is negative in some patients with severe atherosclerosis that puts under the doubt the key role of RAS in pathogenesis of vascular remodeling in some cases. Further researches of mechanisms that influence the level of RAS tissue components expression are needed. The studies of low susceptibility cause of mammary arteries to atherosclerosis in high RAS activity in the presence of severe lesions of arteries at other sites are required. Probably the study of efficacy of RAS inhibitors in patients with various AT1R tissue expressions will allow to develop the prognostic methods of therapy efficiency and to individualize the treatment.

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