Role of aging regulatory protein WRN in cardiac fibrosis
Description: [Background/Introduction] Aging is known to be one of the primary causes of heart failure. Werner syndrome is one of the aging disorder that caused by dysfunction of DNA helicase-regulatory protein (WRN). [Results] WRN-K577M exhibited diffuse left-ventricular (LV) hypertrophy, enhanced fibrosis, and diastolic LVdysfunction with preserved systolic ejection fraction. DNA microarray analysis of WRN-K577M heart revealed that the 253 genes were upregulated including hypertrophy, fibrosis, inflammation, and oxidative stress. Notably, p62 and LC3-II/I were increased in myocardium of WRN-K577M. Blockade of the lysosomal fusion into autophagosome by systemic treatment with chloroquine reduced LC3-II/I ratio.[Conclusion(s)] In WRN-mutant progeria model, off-rate disorder of cardiac autophagy is, at least in part, the cause of increase in oxidative stress and inflammation in heart leading to HFpEF.
Amount: ¥4,680,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2016-04-01
End date: 2019-03-31
Investigator: Yasuko K. Bando
Institution: Nagoya University
Funded outputs count: 1
Funder award ID: 16K09496
OpenAlex ID: G1266719043