Sumoylation of SERCA2a and Cardiovascular Disease

Abstract

Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMO1 in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation.

1 - 15 . (canceled) 
     
     
         16 . A method of diagnosing a propensity to develop heart failure comprising determining the amino acid corresponding to a position selected from the group consisting of any of positions 479-482 and/or position 584-587 of human SERCA2a (SEQ ID NO:2). 
     
     
         17 . A method of diagnosing a propensity to develop heart failure comprising determining the polynucleotide sequence encoding an amino acid corresponding to any of amino acids 479-482 or 584-587 of human SERCA2a (SEQ ID NO:1). 
     
     
         18 . A method of diagnosing a propensity to develop heart failure comprising determining the level of expression of SUMO1 in a cardiomyocyte of a subject and comparing that level to the level of expression of SUMO1 in a cardiomyocyte of a healthy control, wherein reduced expression of SUMO1 relative to the control is indicative of a propensity to develop cardiac failure. 
     
     
         19 . (canceled)