PKM and cardiac hypertrophy: Interestingly, the hearts of E18 knockout mice displayed reduced size, a lower heart-to-body weight ratio, fewer CMs, decreased expression of cell cycle markers, increased levels of the cell cycle inhibitor p27, downregulated PKM2 downstream targets expression including β-catenin, c-Myc, and CCND1, and elevated markers of cardiac hypertrophy such as ANP and BNP [70].