Background: Natriuretic peptide system (NPS) alterations are involved in pathogenesis of
diabetic cardiomyopathy (DCM) and nephropathy (DN), however its epigenetic regulation is still unclear.
Interestingly, histone acetylation epigenetically regulates neprilysin expression in Alzheimer’s
Objectives: The present study was aimed at delineating role of histone acetylation in regulation of NPS
in DCM and DN.
Methods: Streptozotocin (55 mg/kg, i.p.)-induced diabetic male Wistar rats were used to mimic pathogenesis
of DCM and DN. After haemodynamic measurements, all the rat’s plasma, heart and kidney
were collected for biochemistry, ELISA, protein isolation and western blotting, RT-PCR and chromatin
immunoprecipitation (ChIP) assay.
Results: Diabetic rats heart and kidney exhibited activation of NF-κB and TGF-β signalling with increased
histone acetyl transferases (PCAF/CBP) expressions and augmented H2AK5Ac, H2BK5Ac,
H3K18Ac, and H4K8Ac levels. ChIP assay results showed increased enrichment of H3K18Ac and
H2BK5Ac at Nppa, Nppb (Heart) and Mme promoter (Heart/Kidney) in diabetic rats. Enrichment of
H2AK5Ac was augmented on Nppa and Mme promoters in diabetic heart, while it remained unchanged
on Nppb promoter in heart and Mme promoter in kidney.
Conclusion: Augmented histone acetylation at promoter regions of NPS gene(s), at least in a part, is
responsible for increased expressions of ANP, BNP and NEP in diabetic heart and kidney. Hence, histone
acetylation inhibitors can be considered as novel therapeutic targets against DCM and DN.