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Registration Number

0215U001390, 0112U000825 , R & D reports

Title

Identification of pharmacological targets responsible for cardiovascular disorders development in diabetes mellitus

Head

Soloviev Anatoly Ivanovych,

Registration Date

26-02-2015

Organization

State Establishment "Institute of Pharmacology and Toxicology National Academy of Medical Science of Ukraine"

Description

Objects of the study - mechanisms of cardiovascular dysfunctions development in diabetes mellitus. Aim and tasks of the study: to identify structures in vascular wall and hart that are responsible for vasospasm and myocardial dysfunction development in experimental diabetes mellitus (DM); no study changes in expression of alpha- and delta-isoforms of protein kinase C (PKС) in rats vessels in DM and to study effect of blocking of these PKC isoforms expression with small interfering RNA (siRNA) on vascular tone, Са2+-homeostasis and К+-current in vascular smooth muscles and myocardium contractility in DM; on the basis of the established changes of functionality in vascular wall and myocardium to develop theoretical pathways for pharmacological correction of vascular and hart dysfunction in DM. Methods of the study - physiological, electrophysiological, pharmacological, mathematical (statistical analysis). The study conducted have shown that in contrast to PKC-alpha the levels of PKC-delta expression are elevated in aorta of rats with streptozotocin-induced experimental DM. PKC-alpha and PKC-delta genes silencing with siRNA effectively restored damaged endothelium-dependent vasodilatation, decreased К+-channelopathy, and increased Са2+-sensitivity in vascular smooth muscles as well as eliminated cardiomyopathical changes in DM. Using of siRNA for certain PKC isoforms is potentially new and perspective method for pharmacological therapeutics of cardiovascular disorders in DM.

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Іванова І.В.
Бойцова Л.В.
Данова І.В.
Добреля Н.В.
Зеленський С.М.
Кізуб І.В.
Клименко К.І.
Конахович Н.Ф.
Куліковська Р.Д.
Мончак І.Л.
Назаркіна Т.І.
Новохацька Т.В.
Паршиков О.В.
Соловйов А.І.
Стрєлков Є.В.
Тишкін С.М.
Хромов О.В.