Pharmaceutical composition for preventing or treating cardiac arrhythmia
A pharmaceutical composition suitable for preventing or treating cardiac arrhythmia is disclosed. The pharmaceutical composition contains, as an active ingredient, a CCN5 protein or a nucleotide encoding the CCN5 protein. The pharmaceutical composition inhibits the pathological activity of CaMKII, which induces cardiac electrical abnormalities that is the main cause of atrial arrhythmia and ventricular arrhythmia, so as to restore the electrical functions, and inhibits the activity of myofibroblasts causing structural abnormalities. Therefore, the pharmaceutical composition can be effectively used in the prevention or treatment of cardiac arrhythmia.
1. A method for treating cardiac arrhythmia, comprising:
administering to a subject in need thereof,
(i) a pharmaceutical composition comprising a recombinant nucleotide molecule that contains a nucleotide sequence encoding a cellular communication network factor 5 (CCN5) protein,
(ii) a pharmaceutical composition comprising an expression vector loaded with a recombinant nucleotide molecule that contains a nucleotide sequence encoding a CCN5 protein,
(iii) a pharmaceutical composition comprising a recombinant virus that contains a nucleotide sequence encoding a CCN5 protein, or
(iv) a pharmaceutical composition comprising a CCN5 protein,
wherein the CCN5 protein of (i), (ii), (iii), and (iv) comprises the amino acid sequence of SEQ ID NO: 1.
2. The method of claim 1 , further comprising administering a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) protein to the subject.
3. The method of claim 1 , wherein the nucleotide sequence encoding the CCN5 protein, of (i), (ii), and (iii), comprises the nucleotide sequence of SEQ ID NO: 2.
4. The method of claim 1 , wherein the recombinant nucleotide molecule of (i) or (ii) contains a promoter sequence operatively linked to the nucleotide sequence encoding the CCN5 protein.
5. The method of claim 4 , wherein the promoter is any one selected from the group consisting of CMV promoter, adenovirus late promoter, vaccinia virus 7.5K promoter, SV40 promoter, HSV tk promoter, RSV promoter, EF1 alpha promoter, metallothionein promoter, beta-actin promoter, human IL-2 gene promoter, human IFN gene promoter, human IL-4 gene promoter, human lymphotoxin gene promoter, and human GM-CSF gene promoter.
6. The method of claim 1 , wherein the recombinant nucleotide molecule of (i) further contains a nucleotide sequence encoding a SERCA2a protein.
7. The method of claim 6 , wherein in the recombinant nucleotide molecule, the nucleotide sequence encoding the SERCA2a protein is at the 5′ end of the nucleotide sequence encoding the CCN5 protein.
8. The method of claim 7 , wherein the recombinant nucleotide molecule contains a self-cleavage sequence located between the nucleotide sequence encoding the SERCA2a protein and the nucleotide sequence encoding the CCN5 protein.
9. The method of claim 8 , wherein the self-cleavage sequence is a nucleotide sequence encoding 2A peptide derived from porcine teschovirus-1 , Thosea asigna virus, equine rhinitis A virus, or foot-and-mouth disease virus.
10. The method of claim 8 , wherein the self-cleavage sequence is a nucleotide sequence encoding 2A peptide derived from porcine teschovirus-1.
11. The method of claim 8 , wherein the self-cleavage sequence is the nucleotide sequence of SEQ ID NO: 6.
12. The method of claim 1 , wherein the expression vector of (ii) is further loaded with a nucleotide sequence encoding a SERCA2a protein.
13. The method of claim 12 , wherein in the expression vector, the nucleotide sequence encoding the SERCA2a protein is at the 5′ end of the nucleotide sequence encoding the CCN5 protein.
14. The method of claim 1 , wherein the expression vector (ii) further contains a self-cleavage sequence located between the nucleotide sequence encoding the SERCA2a protein and the nucleotide sequence encoding the CCN5 protein.
15. The method of claim 1 , wherein the expression vector of (ii) is any one selected from the group consisting of a plasmid vector and a cosmid vector.
16. The method of claim 1 , wherein the recombinant virus of (iii) is any one selected from the group consisting of adenovirus, adeno-associated viruses (AAV), retrovirus, lentivirus, herpes simplex virus, and vaccinia virus.
17. The method of claim 1 , wherein the recombinant virus of (iii) further contains a nucleotide sequence encoding a SERCA2a protein.