Cardiomyocyte survivin protein expression is associated with cell size and DNA content in the failing human heart and is reversibly regulated after ventricular unloading

Background Mechanical support in congestive heart failure ( CHF) by a left ventricular assist device(LVAD) is associated with decreased cardiac hypertrophy and altered cardiomyocyte molecular pathways. Survivininitiates cell cycle progression by increased cyclinD1/cdk4 complexes by abrogation of the inhibitory effect of p16 INK4a on cdk4. Accordingly, the role of survivinin CHFand after unloading was explored. Methods In 20 myocardial samples from patients with terminal CHF(before and after LVAD), the protein expression of survivin, cyclin D1, cdk4, p16 INK4a , and proliferating cell nuclear antigen(PCNA) was immunohistochemically investigated and morphometrically quantified by calculating the percentage of positive cardiomyocytes per visual field. These data were correlated with cardiomyocyte size and DNA content. Results The mean percentage of cardiomyocytes immunoreactive against survivin, cyclin D1, cdk4, p16 INK4a , and PCNA was significantly increased in CHFcompared with controls and significantly decreased after unloading (57.6% to 26.6%, 42% to 18.3%, 45.4% to 15.3%, 73.0% to 60.5%, and 43.5% to 25.2%, respectively; p r = 0.405; r = 0.563) and DNA content ( r = 0.430; r = 0.480), both in CHF(cardiac remodelling) and after unloading ( p Conclusions These data indicate that survivinis reversibly regulated by ventricular unloading and might be involved in cell size/DNA content regulation and cardiomyocyte proliferation in cardiac remodelling during CHF. It is suggested that after ventricular unloading, decreased survivinprotein expression might contribute to cardiac hypertrophy decrease by lowering the number of cyclin D1/cdk4 complexes.