CDKN2B and systolic heart failure: CCND2 (cyclin D2), which was implicated in cardiac hypertrophy, was downregulated (68), but so was the cyclin-dependent kinase inhibitor CDKN2B. TP53, a major player in the development of systolic heart failure (69, 70), was downregulated, as was PRKCA. Activation of PKCα is implicated in cardiac hypertrophy and heart failure (71–73).