A Novel Cardiac‐Specific Isoform of the Cell Cycle‐Related Kinase (CCRK) Protects the Heart Following Chronic Pressure Overload

One approach to discovering novel targets for heart failure (HF) therapy is to determine which genes are down‐regulated in HF. We found that cardiac cell cycle‐related kinase (cCCRK), a novel isoform of CCRK in the heart, is down‐regulated in heart failure. We generated a cardiac‐specific transgenic (TG) mouse model to test the hypothesis that cCCRK over‐expression protects against HF following chronic pressure overload. Both wild type (WT) and TG mice were submitted to aortic banding for two weeks, and compared to sham‐operated animals. In shams, no significant differences were found between TG and WT in terms of left ventricular (LV) size and function, e.g., LV ejection fraction (EF) was similar (TG 71±1% vs WT 72±1%). After two weeks of pressure overload, LV ejection fraction was significantly impaired in WT (62±2%, P<0.05 vs sham), but maintained in TG (71±2 %, P<0.05 vs WT) and lung/tibial length ratio, an index of pulmonary congestion and HF, was lower (p<0.05) in TG( 9.9±1) vs WT (13.1±1). Therefore, over‐expression of a cardiac‐specific variant of CCRK preserves cardiac function following chronic pressure overload.