Molecular modeling as a new approach to the development of urokinase inhibitors.

Proteolytic activity of urokinase plays an important role in negative remodeling of blood vessels, restenosis, tumor angiogenesis, and metastasizing, which necessitates the development of selective urokinase inhibitors. Using methods of computer modeling (docking, post processing, and direct docking) and quantum chemistry, we selected substances from the large compound database, analyzed their structures, and experimentally verified their inhibitor activity. New urokinase inhibitor candidates were proposed based on the theoretical predictions and experimental verification of compound activities.

Proteolytically inactive recombinant forms of urokinase suppress migration of endothelial cells.

Proteolytically inactive recombinant forms of urokinase (uPAHQ and amino-terminal fragment) inhibit spontaneous migration of endothelial cells; amino-terminal fragment also suppresses angiogenesis stimulated by basic fibroblast growth factor in vitro. These findings suggest the possibility of using synthesized proteolytically inactive recombinant forms of urokinase for the regulation of endothelial cell migration and suppression of neoangiogenesis.

[Analysis of morpho-functional parameters of the heart and polymorphisms of Renin-Angiotensin-aldosterone system genes in patients with different variants of the course of hypertrophic cardiomyopathy].

Background: Clinical course and prognosis of a hereditary myocardial disease hypertrophic cardiomyopathy (HCMP) is determined by multiple factors most of which have genetic nature.

Aim: To study morpho functional parameters of the heart and polymorphisms of renin angiotensin aldosterone system genes in patients with various variants of the course of HCMP: stable variant (18%), atrial fibrillation (20%), progressing variant (51%), sudden cardiac death (9%) and "terminal stage" of disease (2%). Control group comprised 55 healthy people (mean age 44.

[Genetic factors of risk of ischemic heart disease development in patients with familial hypercholesterolemia].

Unlabelled: Ischemic heart disease (IHD) develops in patients with familial hypercholesterolemia (FHC) 15-20 years earlier than in general population. However age of onset of the disease, its clinical manifestations are variable and not completely determined by cholesterol level and class of low density lipoprotein receptor mutations.

Aim: To elucidate associations of some auxiliary genetic factors -- such as C151565T, C677T, R353Q polymorphisms of glycoprotein IIIa (GPIIIa), methylenetetrahydrofolate reductase (MTHFR) and coagulation factor VII genes, respectively, -- with the presence of IHD in patients with FHC.