Sumoylation of SERCA2a and cardiovascular disease
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. A method of treating a cardiac dysfunction in a subject comprising administering a recombinant adeno-associated virus vector comprising an expressible coding region encoding a SUMO1 protein, wherein the coding region is operably linked to at least one expression control element, in a therapeutically effective amount to treat the cardiovascular dysfunction in the subject, wherein the cardiac dysfunction is selected from the group consisting of heart failure, pressure overload-induced cardiac dysfunction, and cardiac dysfunction induced by inhibited calcium decay.
2. The method according to claim 1 wherein the heart failure comprises contractile dysfunction.
3. The method according to claim 1 wherein the heart failure is TAC-induced heart failure.
4. The method according to claim 1 wherein the subject is a human.
5. The method according to claim 1 wherein the recombinant adeno-associated virus is rAAV1.