Cardiovascular Faculty

Research Interests

Our research goal is to understand the biology and biochemistry of serine proteases, receptors and hormones which are involved in the regulation of natriuretic peptide system, and to evaluate their potential for diagnostic applications or rational drug-based therapies in particular for cardiovascular disorders such as hypertension and heart failure.

Atrial natriuretic peptide (ANP) plays a critical role in maintaining normal arterial blood pressure and blood volume, and is involved in major cardiovascular diseases such as hypertension and heart failure. ANP is primarily synthesized and stored in atrial cardiomyocytes as a pro-peptide (pro-ANP). It is secreted upon atrial stretch into the circulation and requires specific proteolytic cleavage to become an active hormone. The type II transmembrane serine protease corin cleaves the pro-ANP and may contribute to the regulation of the natriuretic peptide system. Abnormal expression and/or regulation of corin could compromise the entire ANP-mediated pathway. We are interested in the regulation activity of corin and correlation between efficiency of pro-ANP activation and heart failure disorders. An understanding of these mechanisms may provide key insights into the regulation of the ANP-signaling cascade. We believe that these insights will translate into new approaches for improving diagnosis and treatment of hypertension and heart failure.  

 

Grant Support

American Heart Association Scientist Development Grant

"Regulation of structure and activity of the cardiomyocyte specific pro-ANP convertase, corin by mast cell proteases": 07.2008-06.2012.

Current Projects

Basic science research projects

• Regulation of structure and activity of the cardiomyocyte specific pro-ANP convertase, corin by mast cell proteases
• Cardiomyocyte-specific serine protease corin regulates blood pressure and heart failure development in the transgenic models of heart failure

Translational medicine research projects

• Cardiac Natriuretic Peptides in Decompensated Heart Failure
• Evaluation of corin level in plasma of patients with acute decompensated heart failure

Selected Publications

1. Gladysheva I.P., King S.M., Houng A.K. N-glycosylation modulates the cell surface expression and catalytic activity of corin. Biochem. Biophys. Research Commun. 2008, 373, 130-135.
2. Gladysheva I.P., Robinson B.R., Houng A.K., Kováts T., King S.M. Corin is co-expressed with pro-ANP and localized on the cardiomyocyte surface in both zymogen and catalytically active forms. Journal of Molecular and Cellular Cardiology. 2008, 44(1), 131-142.
3. Sazonova I.Y., Thomas B.M., Gladysheva I.P., Houng A.K., Reed, G.L. Fibrinolysis is amplified by converting a2-antiplasmin from a plasmin inhibitor to a substrate. Journal of Thrombosis and Haemostasis. 2007, 5 (10), 2087-2094.
4. Gladysheva I.P., Sazonova I.Y., Houng A., Hedstrom L., Reed G.L.  Regulation of non-proteolytic active site formation in plasminogen. Biochemistry. 2007, 46 (30), 8879-8887.
5. Sazonova IY, Robinson BR, Gladysheva IP, Castellino FJ, Reed GL. alpha Domain deletion converts streptokinase into a fibrin-dependent plasminogen activator through mechanisms akin to staphylokinase and tissue plasminogen activator. J. Biol. Chem. 2004, 279 (24), 24994-25001.
6. Gladysheva IP, Turner RB, Sazonova IY, Liu L, Reed GL. Coevolutionary patterns in plasminogen activation. Proc Natl Acad Sci U S A. 2003, V.100 (16), 9168-9172.
7. Gladysheva I.P., Sazonova I.Y., Chowdhry, S.A., Liu L., Turner R.B., Reed G.L. Chimerism reveals a role for the streptokinase beta-domain in nonproteolytic active site formation, subsrate, and inhibitor interactions. J. Biol. Chem. 2002, 277 (30), 26846-26851.
8. Gladysheva I.P., Moroz N.A., Karmakova T.A., Nemtsova E.R., Yakubovskaya R.I., Larionova N.I. Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. J. Drug Targeting 2001, 9, 303-316.
9. Gladysheva I.P., Polekhina O.V., Karmakova T.A., Nemtsova E.R., Yakubovskaya R.I., Shen W.-C., Kennedy A.R., Larionova N.I. Potential of block copolymer- and immuno-conjugates for tumor-targeted delivery of Bowman-Birk soybean protease inhibitor. J. Controlled Release 2001, 74 (1-3), 303-308.
   

Recognition

• Coming soon

Training

• (Postdoctoral Training) M.V.Lomonosov Moscow State University, Moscow, Russia
• (Postdoctoral Training) Harvard School of Public Health, Harvard University, Boston, MA
• Ph.D., M.V.Lomonosov Moscow State University, Moscow, Russia
• MS, M.V.Lomonosov Moscow State University, Moscow, USSR

Links

• None

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