| First Author | Cooley N | Year | 2013 |
| Journal | Circ Heart Fail | Volume | 6 |
| Issue | 2 | Pages | 318-25 |
| PubMed ID | 23258573 | Mgi Jnum | J:252072 |
| Mgi Id | MGI:6107599 | Doi | 10.1161/CIRCHEARTFAILURE.112.972158 |
| Citation | Cooley N, et al. (2013) No contribution of IP3-R(2) to disease phenotype in models of dilated cardiomyopathy or pressure overload hypertrophy. Circ Heart Fail 6(2):318-25 |
| abstractText | BACKGROUND: We investigated the contribution of inositol(1,4,5)-trisphosphate (Ins(1,4,5)P3 [IP3]) receptors (IP3-R) to disease progression in mouse models of dilated cardiomyopathy (DCM) and pressure overload hypertrophy. Mice expressing mammalian sterile 20-like kinase and dominant-negative phosphatidylinositol-3-kinase in heart (Mst1xdn-PI3K-2Tg; DCM-2Tg) develop severe DCM and conduction block, associated with increased expression of type 2 IP3-R (IP3-R(2)) and heightened generation of Ins(1,4,5)P3. Similar increases in Ins(1,4,5)P3 and IP3-R(2) are caused by transverse aortic constriction. METHODS AND RESULTS: To evaluate the contribution of IP3-R(2) to disease progression, the DCM-2Tg mice were further crossed with mice in which the type 2 IP3-R (IP3-R(2)-/-) had been deleted (DCM-2TgxIP3-R(2)-/-) and transverse aortic constriction was performed on IP3-R(2)-/- mice. Hearts from DCM-2Tg mice and DCM-2TgxIP3-R(2)-/- were similar in terms of chamber dilatation, atrial enlargement, and ventricular wall thinning. Electrophysiological changes were also similar in the DCM-2Tg mice, with and without IP3-R(2). Deletion of IP3-R(2) did not alter the progression of heart failure, because DCM-2Tg mice with and without IP3-R(2) had similarly reduced contractility, increased lung congestion, and atrial thrombus, and both strains died between 10 and 12 weeks of age. Loss of IP3-R(2) did not alter the progression of hypertrophy after transverse aortic constriction. CONCLUSIONS: We conclude that IP3-R(2) do not contribute to the progression of DCM or pressure overload hypertrophy, despite increased expression and heightened generation of the ligand, Ins(1,4,5)P3. |
