Hdac8 Inhibitor Alleviates Transverse Aortic Constriction-Induced Heart Failure in Mice by Downregulating Ace1

Figure 8

Suppression of HDAC8 attenuates fibrosis, inflammation, cardiac dysfunction, and pulmonary congestion in heart failure. Schematic diagram depicting the Hdac8 selective inhibitor- (PCI34051-) mediated or Hdac8 short-interfering RNA-mediated inhibition of transverse aortic constriction- (TAC-) induced heart failure. TAC-mediated pressure overload upregulates the expression of Hdac8 and Ace1 and downregulates the expression of Ace2 in the heart and lungs. In cardiomyocytes, overexpression of Hdac8 upregulates the expression of Ace1 and downregulates the expression of Ace2. PCI34051 treatment or Hdac8 knockdown mitigates TGF-β1-induced upregulation of p-Smad2/3, Col1a1, Fn1, and Acta2 in vitro. PCI34051 regulates the TNFα-mediated or Ace1 overexpression-mediated expression of Rela and Nfkbia. PCI34051 alleviates cardiac hypertrophy and dysfunction, inflammation, fibrosis, and pulmonary congestion in heart failure.