Remodeling of gap junctions in XXXX hearts hypertrophied by forced @entity1968 signaling.

@entity1 @entity16899 @entity1165 @entity21043 @entity4879 @entity19 @entity384 @entity12401 @entity16898 @entity8384 @entity943 @entity1968
BACKGROUND: @entity8384 - @entity4879 @entity19 express a constitutively active (truncated) form of the @entity1 @entity1968 receptor which triggers development of @entity384 . In those hearts, we studied expression of gap junction proteins in relation to electrical impulse propagation. METHODS AND RESULTS: As compared to wildtype @entity19 , hearts of 4-6 month old @entity19 with 7-12 inserted @entity4879 copies are marked by an increased heart weight/body weight- and heart weight/tibia length ratio. 3-extremity lead ECGs revealed prolongation of the Q-j interval suggesting delayed ventricular activation. Mapping of electrical activity of epi- and endocardial left ventricular free wall revealed activation delay, increased heterogeneity in conduction and regional conduction block. @entity1165 did not occur spontaneously nor could be induced by ventricular pacing. Immunohistochemical analysis showed profound and heterogeneous redistribution and down-regulation of the gap junction protein @entity16899 ( @entity16899 ) in the left ventricular free wall. Here, @entity4879 expression induced re-expression of the hypertrophic markers alpha-skeletal actin and @entity8384 , and in 3 out of 10 severely affected @entity19 , re-expression of @entity16898 . Concomitant with changes in expression/distribution of @entity16899 , changes in expression and distribution of @entity12401 and @entity21043 (two other intercalated disk associated proteins) were observed. CONCLUSIONS: @entity8384 - @entity4879 transgenic hearts show heterogeneous re-expression of (early) sarcomeric genes while expression of @entity16899 , @entity21043 and @entity12401 is down-regulated. We postulate that the resulting aberrant ventricular activation does not trigger development of @entity943 due to the small size of remaining healthy ventricular tissue where the transgene is not expressed.
