B cell lymphoma 11b (Bcl11b) is a zinc finger transcription factor with dual action (repression/activation). It is involved in various physiological responses under healthy and pathological conditions. Genetic variations in the locus harboring this gene are associated with increased risk for cardiovascular disease making it relevant to analyze its role in the heart.

Our aims are: (1) To analyze cardiac function in the absence of Bcl11b. (2) To investigate the role of Bcl11b in the onset of pathological cardiac hypertrophy.

To achieve the goals, we conducted experiments on both in vivo and in vitro models.

In vivo, the impact of Bcl11b on cardiac function, morphology, and molecular pathways were analyzed in cardiac-specific Bcl11b knockout mice induced by tamoxifen administration.

In vitro, Bcl11b deletion was induced by recombinase Cre via adenovirus infection in isolated newborn primary cardiac cell. Cardiomyocytes were stimulated by angiotensin II or phenylephrin to induce cell hypertrophy and then analyzed.

Invalidation of Bcl11b specifically in cardiomyocytes (Bcl11b HKO mice) results in cardiac cell death accompanied by inflammation, fibrosis, a moderate cardiac hypertrophy and decreased contractile function. Fibrosis was observed as soon as week and increased over time. Further examination of 1-week mutant hearts revealed the presence of “dead cell” zones and macrophage invasion. This was preceded by the detection of IgG positive cardiomyocytes that suggest compromised membrane integrity. At the molecular level, the expression of genes related to inflammation/repair and cell death was increased in the mutant heart. Finally, echocardiographic analysis showed a 10% decrease in ejection fraction and fractional shortening in mutant mice as compared to control.

The cardiac specific Bcl11b KO mice exhibit diminished heart function, increased fibrosis and cell death. Thus, Bcl11b could play a role in the maintenance of cardiac homeostasis and in the cardiac damage response.