GRK2 and heart failure: This controversy on GRK2 has also been described in cardiac hypertrophy with preserved or reduced ejection fraction (EF) in rats, in which it was shown that GRK2 was down-regulated in animals with heart failure with preserved EF (HFpEF), and it was upregulated in animals with reduced EF (HFrEF), with the latter confirming the importance of GRK2 in HFrEF manifestation [144].