@entity34323 -mediated decreased neutrophil apoptosis is a determinant of impaired coronary collateral growth in XXXX .

@entity35 @entity1976 @entity2310 @entity168 @entity1563 @entity209 @entity34323
UNASSIGNED: Coronary collateral growth (CCG) is @entity209 . @entity34323 is a pro-proliferative and anti-apoptotic microRNA (miR), which we showed to be elevated in @entity209 . Here we investigate whether impaired CCG in @entity209 involved @entity34323 -mediated aberrant apoptosis. Normal ( @entity168 ) and @entity209 (JCR) @entity35 underwent transient, repetitive @entity1563 (RI). Anti-apoptotic @entity1976 , p-Bad and @entity1976 / @entity2310 dimers were increased on days 6 and 9 RI and pro-apoptotic @entity2310 and @entity2310 / @entity2310 dimers and cytochrome c release concurrently decreased in JCR vs. @entity168 @entity35 . Active caspases were decreased in JCR vs. @entity168 @entity35 (~50%). Neutrophils increased transiently on day 3 RI in the collateral-dependent zone (CZ) of @entity168 @entity35 but remained elevated in JCR @entity35 paralleling @entity34323 expression. @entity34323 downregulation by antimiR-21 induced neutrophil apoptosis and decreased @entity1976 and @entity1976 / @entity2310 dimers (~75%) while increasing @entity2310 / @entity2310 dimers, cytochrome c release and caspase activation (~70%, 400% and 400%). AntimiR-21 also improved CCG in JCR @entity35 (~60%). Preventing neutrophil infiltration with blocking antibodies resulted in equivalent CCG recovery confirming a major role for deregulated neutrophil apoptosis in CCG impairment. Neutrophil and @entity34323 -dependent CCG inhibition was in significant part mediated by increased oxidative stress. We conclude that neutrophil apoptosis is integral to normal CCG, and that inappropriate, prolonged @entity34323 -mediated survival of neutrophils plays a major role in impaired CCG, in part via oxidative stress generation.
