Role of brain serotonin dysfunction in the pathophysiology of congestive heart failure

► BALB/c mice have brain serotonin dysfunction due to a SNP in tryptophan hydroxylase 2. ► Knock-in mice bearing a sarcomeric protein mutation that causes DCM were created. ► BALB/c mice, but not C57Bl/6 mice, developed severe congestive heart failure (HF). ► Drugs to increase brain serotonin function ameliorated HF in BALB/c mice. ► Brain serotonin may play an important role in the development of congestive HF in DCM.